Methods. We performed a 4-year prospective follow-up study in 231 chronic PD patients from a single regional dialysis centre in Hong Kong. Valvular calcification was detected using echocardiography, and fasting venous blood was collected to measure a panel of inflammation markers. The patients were stratified into five groups on the basis of 0, 1, 2, 3 and all 4 inflammation and calcification risk markers, namely high C-reactive protein (CRP) (CRP in upper tertile), high interleukin-6 (IL-6) (IL-6 in upper tertile), low fetuin-A (fetuin-A in lower tertile) and valvular calcification. Study outcomes included all-cause and cardiovascular mortality and fatal or non-fatal cardiovascular events (CVEs).

Results. The patients with 4, 3, 2 and 1 markers had an adjusted hazard ratio (HR) of 5.17 (95% CI, 1.81–14.77, P = 0.002), 3.38 (95% CI, 1.50–7.60; P = 0.003), 2.17 (95% CI, 0.98–4.77; P = 0.056) and 2.42 (95% CI, 1.18–4.96; P = 0.016), respectively, for mortality at 4 years than those with 0 risk marker. The adjusted HRs for fatal or non-fatal CVEs were 4.33 (95% CI, 1.70–11.03; P = 0.002), 1.60 (95% CI, 0.73–3.52; P = 0.24), 1.92 (95% CI, 0.95–3.90; P = 0.07) and 1.33 (95% CI, 0.67–2.62; P = 0.42), respectively, for patients with 4, 3, 2 and 1 markers than those with 0 risk markers.

Conclusions. A composite of inflammation and calcification markers provides long-term prognostication and identifies the sickest PD patients with the worst clinical outcomes. Since these parameters can all be obtained quite readily, our data support the adoption of a multiinflammation and calcification risk marker approach for mortality and cardiovascular risk stratification in PD patients.

Methods. We investigated the frequency, predictors, treatment and clinical outcomes of Corynebacterium peritonitis in all Australian adult patients involving 66 centres who were receiving PD between 1 October 2003 and 31 December 2006.

Results. Eighty-two episodes of Corynebacterium peritonitis (2.3% of all peritonitis episodes) occurred in 65 (1.4%) PD patients. Ten (15%) patients experienced more than one episode of Corynebacterium peritonitis and additional organisms were isolated in 12 (15%) episodes of Corynebacterium peritonitis. The incidence of Corynebacterium peritonitis was significantly and independently predicted only by BMI: RR 2.72 (95% CI 1.38–5.36) for the highest tertile BMI compared with the lowest tertile. The overall cure rate with antibiotics alone was 67%, which was similar to that of peritonitis due to other organisms. Vancomycin was the most common antimicrobial agent administered in the initial empiric and subsequent antibiotic regimens, although outcomes were similar regardless of antimicrobial schedule. Corynebacterium peritonitis not infrequently resulted in relapse (18%), repeat peritonitis (15%), hospitalization (70%), catheter removal (21%), permanent haemodialysis transfer (15%) and death (2%). The individuals who had their catheters removed more than 1 week after the onset of Corynebacterium peritonitis had a significantly higher risk of permanent haemodialysis transfer than those who had their catheters removed within 1 week (90% versus 43%, P < 0.05).

Conclusions. Corynebacterium is an uncommon but significant cause of PD-associated peritonitis. Complete cure with antibiotics alone is possible in the majority of patients, and rates of adverse outcomes are comparable to those seen with peritonitis due to other organisms. Use of vancomycin rather than cephazolin as empiric therapy does not impact outcomes, and a 2-week course of antibiotic therapy appears sufficient. If catheter removal is required, outcomes are improved by removing the catheter within 1 week of peritonitis onset.

Methods. We explored the cross-sectional association between duration of PMH use and albuminuria in 2445 post-menopausal, non-diabetic women from the Nurses’ Health Study. Women were categorized as hormone non-users, past users or current users grouped by 3-year intervals of duration of use, from ≤3 years to >15 years. The outcome was the top decile of urine albumin/creatinine ratio (ACR). Multivariate logistic regression was used to assess the association between duration of PMH use and risk of being in the top decile.

Results. The mean age was 66.8 years, and 57% were currently using PMH. The median ACR was 2.9 mg/g, and the 90th percentile was 9.2 mg/g. Compared with women with no history of PMH use, the odds ratio for being in the top ACR decile was lower for women with use of >6–9 years, >9–12 years, >12–15 years and >15 years, but there was no dose–response. The overall odds ratio was 0.55 (95% CI: 0.39–0.77) among women with >6 years of current PMH use compared with non-users. Current hormone use of shorter duration and past hormone use were not associated with albumin excretion.

Conclusions. Current PMH use of >6 years is associated with a lower urinary ACR in non-diabetic women.

Methods. Nineteen chronic HD patients who were treated with low-flux HD for at least 2 months were included in the Dutch CONvective TRAnsport STudy (CONTRAST). After randomization, 10 patients continued low-flux HD and 9 patients switched to post-dilution HDF. The present study describes various parameters of PLT activation and degranulation at baseline (during HD) and after 3 months (during HDF) in the latter group of patients. At both time points, multiple blood samples were drawn. During the first 30 min of treatment, differences over the extracorporeal circuit (ECC) were calculated by taking samples from both afferent (arterial) and efferent (venous) lines. Correlations between various parameters were calculated in the total group of patients after 3 months.

Results. Immediately after the start of HD, PLT counts dropped over the ECC. During HDF, PLT counts decreased even more and reached a nadir at t30. CD62p expression increased early during HD and returned to baseline thereafter. During HDF, these changes were more pronounced and more protracted. With respect to degranulation, rather dissimilar results were obtained. During HD, both PF4 and BTG increased over time, whereas during HDF, PF4 increased but BTG did not change. Haemoconcentration and transmembrane pressure (TMP) within the dialyser were, respectively, ~10 and 3x higher during HDF than during HD. There was a striking correlation between the changes in haemoconcentration and the changes in both PLT counts and CD62p over the ECC.

Summary and Conclusions. PLT activation, as measured by the expression of CD62p, was more pronounced and more protracted during HDF than during HD. During HDF, PLTs were trapped abundantly within the ECC, not only after first passage, but also thereafter. The degranulation product BTG increased during HD, but did not change during HDF. These observations may well be explained by the greater haemoconcentration and/or higher TMP during HDF on the one hand, and superior convective transport at the other. Whether the potential harmful effects of enhanced PLT activation are counterbalanced by the beneficial effects of an increased convective transport of degranulation products remains to be established.

Methods. A total of 133 non-dialyzed CKD patients at various stages of kidney disease [75 males/58 females, median age: 69.9 (27.4–94.6)] were enrolled, excluding extrarenal replacement therapy patients. All underwent chest multidetector computed tomography for CAC scoring. Blood samples were collected for measurement of vascular risk markers (kidney disease, inflammation, nutrition, calcium phosphate and OPG). A potential relationship between CAC and these biological markers was investigated, and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of involved markers that best predicted the presence of CAC.

Results. After adjustment for age, diabetes, smoking and gender, among biological markers, only low-estimated glomerular filtration rate using Modification of Diet in Renal Disease [OR = 3.63 (1.10–12.02)], high FEPO₄ [OR = 3.99 (1.17–13.6)] and high OPG levels [OR = 8.54 (2.14–34.11)] were associated with the presence of CAC. A protective effect of 1.25(OH)₂ vitamin D [OR = 0.20 (0.05–0.79)] and LDL cholesterol [OR = 0.27 (0.08–0.94)] on CAC was also observed. ROC curve analysis showed that the OPG best cut-off value predicting CAC was 757.7 pg/mL.

Conclusion. These results suggest that a CAC increase is strongly associated with a plasma OPG increase in CKD patients. The values of OPG >757.7 pg/mL allow us to predict the presence of CAC in these patients.

Methods. Over a period of 7 years, 74 consecutive patients underwent angiography of an immature fistula that showed either stenosis or an insufficient enlargement of the radial artery that was treated by percutaneous dilation. Success, complications and secondary interventions were recorded according to consensus definitions. Patency following angioplasty was estimated with the Kaplan–Meier technique.

Results. The mean patient age was 70 years, 44% were women, 69% had diabetes, 23% were smokers, 76% had hypertension, 64% had coronary disease and 46% had peripheral artery occlusive disease. Concomitant venous stenosis was diagnosed in 53% of patients. Arterial stenosis was >5 cm long in 53 cases. Technical success was achieved in 73/74 cases following angioplasty. All but two fistulas were then successfully used for dialysis. Dilation-induced rupture occurred in 13 cases (17%) but required only two stent placements. Five cases (7%) of hand ischaemia within 1 month of dilation were treated successfully by ligation of the distal artery. Primary patency rates at 12 and 24 months were significantly better for pure arterial lesions, with 65% and 61% compared to 42% and 35% in cases of concomitant venous stenosis (P < 0.04). The secondary patency rates were 96% and 94% at 1 and 2 years, respectively.

Conclusion. Dilation of the radial artery yields higher patency rates than for veins. Surgeons might therefore be less demanding about the initial quality of the radial artery prior to creation of radial-cephalic fistulas.

Objective. The aim of this study was to compare the categorization of the sodium sieving effect in peritoneal dialysis (PD) patients by 2.27% and 3.86% PETs, and to disclose clinical correlates of this phenomenon.

Method. Ninety PD patients underwent prospectively 2.27% and 3.86% modified (dialysate samples at 0, 60, 90, 120 and 240 min) PETs, in a random order. We searched for differences in the time profiles of sodium sieving and its categorization. We correlated sodium sieving with ultrafiltration (UF) and solute transport capacity, as also with selected clinical and demographic variables, using a multivariate approach.

Results. The maximum dip in the dialysate sodium concentration (11.1 mM/L, 3.86% versus 7.1 mM/L, 2.27%, P < 0.001) was most common after 90 min in the 3.86% PET, with the 2.27% test somewhere between 60 and 90 min. Low sodium sieving (defined by a dip <5 mM/L at 60 min) was observed in 8.9% of the patients in the 3.86% test. The same limit categorized 34.4% of the patients as low sieving in the 2.27% test (100.0% sensitivity and 72.0% specificity, using 3.86% as a reference). UF and D/P_{240 min} creatinine were independent predictors of the sodium sieving effect in both tests. Moreover, multivariate analysis disclosed a consistent inverse correlation between GFR and sodium sieving in both the 2.27% (B = –0.23, 95% CI –0.40, –0.07, P = 0.006) and 3.86% PET (B = –0.46, 95% CI –0.65, –0.26, P < 0.0005).

Conclusions. The standard 2.27% PET permits some categorization of sodium sieving in PD patients. However, the information provided by this test lacks the discriminatory capacity of the 3.86% PET, which should be considered the one for reference for this purpose. GFR keeps a consistent inverse correlation with the intensity of sodium sieving in both the 2.27% and 3.86% PET.

Methods. In 41 male and 39 female patients with type 2 diabetes, renal plasma flow (RPF) was determined by constant infusion input clearance at baseline and following infusion of the NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA, 4.25 mg/kg) to assess basal renal vascular NO availability. After a subsequent infusion of l-arginine (100 mg/kg) to restore baseline conditions, vitamin C (45 mg/kg) was co-infused to determine levels of oxidative stress in the renal circulation.

Results. Baseline renal haemodynamics were similar between genders. l-NMMA-induced renal vasoconstriction was more pronounced in females compared to males (–89 ± 69 versus –60 ± 52 ml/min/1.73 m², P = 0.03). After administration of l-arginine to restore baseline perfusion, the co-infusion of vitamin C led to a lesser increase of RPF in females than in males (+37 ± 86 versus +60 ± 52 ml/min/1.73 m², P = 0.05).

Conclusions. Our data demonstrate that NO availability in the renal circulation is greater in female than in male patients with type 2 diabetes that is associated with reduced levels of oxidative stress in females. The role of this gender-related difference in renal endothelial function for the initiation and progression of diabetic nephropathy should be addressed in future studies.

Methods. To assess whether MYH9 was associated with T2DM-ESRD, 751 African Americans with T2DM-ESRD, 227 with T2DM lacking nephropathy and 925 non-diabetic non-nephropathy controls were genotyped for 14 MYH9 SNPs. Association analyses used SNPGWA and Dandelion.

Results. Comparing T2DM-ESRD cases with non-diabetic controls, single SNP associations were detected with 8 of 14 SNPs, gender- and admixture-adjusted P-values 0.047–0.005 [recessive model, odds ratio (OR) range 1.30–1.55]. The previously associated MYH9 E1 and L1 haplotypes were associated with T2DM-ESRD (E1: OR 1.27, 95% CI 1.04–1.56, P = 0.021 recessive and L1: OR 1.43, 95% CI 1.09–1.87, P = 0.009 dominant). Contrasting the 751 T2DM-ESRD cases with 227 T2DM non-nephropathy controls revealed that E1 haplotype SNPs rs4821480, rs2032487 and rs4821481 were associated with kidney failure (OR 1.38–1.40 recessive, all P < 0.048). Among E1 and L1 risk homozygotes, respectively, mean (SD) diabetes duration prior to renal replacement therapy was 16.6 (9.7) and 16.4 (10.0) years, and 65% had diabetic retinopathy.

Conclusions. Genetic dissection of T2DM-associated ESRD reveals that MYH9 underlies a portion of this clinically diagnosed disorder in African Americans. It is likely that a subset of African Americans with T2DM and coincident nephropathy have primary MYH9-related kidney disease (e.g. FSGS or global glomerulosclerosis), although renal biopsy studies need to be performed.

Methods. We detected genetic polymorphisms by the TaqMan® method and by sizing PCR amplicons (n = 486). The primary outcomes were early acute rejection (EAR) and repeated early acute rejection (RR). We defined EAR as the occurrence of a biopsy-proven AR within 3 months after transplantation.

Results. The development of EAR was dependent on the number of A alleles in recipients and showed a dose–response relationship (P = 0.002). When we combined the number of A alleles in both donor and recipient, episodes of EAR and RR were more prevalent as the allelic number increased (A allelic number 0 & 1, 2 versus 3 & 4, P = 0.048; 0 & 1 versus 3 & 4, P = 0.006). Statistical significance was preserved after multivariate analysis of sex, HLA mismatch and type of donor with the recipient's age as the continuous term. Also, graft survival was different according to the presence of the A allele, i.e. recipients carrying A allele (+) grafts showed poor graft survival (P = 0.008 by a log-rank test). Again, the number of A alleles affected graft survival as the recipients who carried more A alleles had poor graft survival (A allele number 0 & 1 versus 2 versus 3 & 4, P = 0.011; 0 & 1 versus 3 & 4, P = 0.08; 0 & 1 versus 2, P = 0.002; by a log-rank test). All of the participants were wild-type homozygotes for CCR532.

Conclusions. The A allele of CCR5 59029G>A was a risk factor for EAR and RR. As the number of A alleles increased, episodes of EAR were more frequently observed.

Methods. Components of the VEGF system were measured (ELISAs) in 185 prevalent HD patients and levels related to clinical characteristics, biochemical markers and survival. The patients were followed up prospectively for a median 31 (20–37) months.

Results. While ischaemic heart disease was independently associated with a lower sVEGFR-2 (OR = 2.75, P = 0.02), sVEGFR-1 was positively associated with IL-6 ( = 0.22, P = 0.003) and white blood cell count ( = 0.22, P = 0.002). In survival analysis, the patients with a high sVEGFR-1 level had a higher all-cause mortality (Kaplan–Meier Chi-Square = 5.6, P = 0.02) and a higher adjusted mortality risk (Cox HR = 1.93, P = 0.009) than those with low levels.

Conclusion. In the first clinical study of sVEGFR-1 and -2 in CKD, we found novel associations between the sVEGFRs and cardiac disease. This may be of clinical importance, as a high sVEGFR-1 was an independent risk factor for all-cause mortality.

Methods. Sixteen hypertensive type 1 diabetic patients with persistent normoalbuminuria (presumed normal autoregulation) completed this randomized, double-masked, crossover trial. After a 4-week wash-out period, patients received spironolactone 25 mg o.d. and matched placebo for 4 weeks in random order. After each treatment period, the ability to autoregulate GFR was determined by measuring GFR (⁵¹Cr–EDTA clearance) before (basal) and after acute blood pressure reduction by intravenous injection of clonidine.

Results. During placebo, the mean (SE) basal GFR was 115 (5) ml/min/1.73 m² and the BP was 146 (4)/81 (2) mmHg corresponding to a MAP of 103 (2) mmHg. Spironolactone did not significantly reduce GFR or BP. Injection of clonidine induced a significant reduction in the MAP of 17 (2) and 19 (1) mmHg during placebo and spironolactone treatment, respectively, and an overall reduction in GFR of 11 and 15 ml/min/1.73 m² (both comparisons NS between treatment periods). Signs of impaired autoregulation were present in nine patients during placebo and in nine patients during spironolactone treatment. Relative changes in GFR on placebo treatment correlated with diabetes duration (R = 0.67, P < 0.01) but were not related to duration of hypertension, baseline BP, GFR, HbA1c or to changes in BP.

Conclusion. Spironolactone did not change the overall ability to autoregulate GFR in 16 hypertensive type 1 diabetic patients with normoalbuminuria. Our data are suggestive that the ability to autoregulate GFR is gradually impaired with increasing diabetes duration, a phenomenon not previously described in normoalbuminuric patients.

Methods. Data were collected prospectively on all patients having PD catheters inserted between 1999 and 2008, including success of insertion, complications and infections.

Results. A total of 283 catheters were inserted percutaneously using a Seldinger technique under sedation and local anaesthesia, and 150 surgically under general anaesthetic. Eighty-six percent of the percutaneous catheters and 66% surgical catheters were first catheters. No major complications occurred. In 7% of the percutaneous patients and 5% surgical patients, the procedure failed or was abandoned. Poor initial drainage occurred in 21% insertions but resolved in most cases and resolved dialysate leak in 6%. Wound infections or peritonitis occurred in 9% and 4% of percutaneous insertions. Only 13% of patients could not use their catheter at 1 month after percutaneous insertion, and 83% of the patients remained on PD using the original catheter at 6 months.

Conclusions. Percutaneous PD catheter insertion was associated with a very low complication rate and high primary success rate, and was highly efficient in use of resources and avoided the need for general anaesthesia.

Methods. Conditionally immortalized human podocytes were cultured for up to 24 h with 375–750 µM palmitate. Functional effects on glucose uptake and ceramide production were measured. Gene expression was investigated using a focused gene array, and protein signalling and trafficking were studied with Western blotting and immunofluorescence.

Results. We found that palmitate blocked insulin-stimulated glucose uptake in human podocytes. This was associated with increased ceramide production, and use of the ceramide inhibitors myriocin and fumonisin B1 partially recovered the insulin sensitivity. At the level of transcription, palmitate downregulated genes associated with several pathways involved in insulin signalling. At the protein level, phosphorylation of the insulin receptor, IRS1 and PKB was reduced and there was impaired translocation of GLUT4 to the cell surface.

Conclusion. This is the first study to demonstrate a direct effect of saturated fatty acids on podocyte function. These findings may represent a novel link between systemic insulin resistance and the development of nephropathy.

Methods. The aim of the present study was to evaluate serum levels of neutrophil gelatinase-associated lipocalin (NGAL), a small siderophore-binding protein, in a cohort of 56 chronic HD patients in order to determine its possible relationships with iron status.

Results. NGAL levels were markedly higher in HD patients than in healthy controls; furthermore, HD patients with TSAT <20% had lower NGAL values than healthy controls, whereas the correction of iron deficiency by means of chronic i.v. iron administration significantly increased NGAL values from baseline. Findings from univariate and multivariate analyses demonstrated that NGAL was a significant predictor of hsCRP, spKT/V and TSAT. In ROC analysis, a NGAL cut-off level of ≤473 ng/mL had a greater sensitivity and specificity than a ferritin level of <200 ng/mL in identifying iron deficiency among HD patients.

Conclusions. The findings demonstrated that HD patients have altered NGAL values probably because this protein is involved in the maintenance of iron equilibrium. Finally, NGAL might be proposed as a new tool in the assessment of iron deficiency and in the management of iron therapy for HD patients.

Methods. We performed a prospective observational study examining the relationship between anti-PC concentrations and mortality risk in a well-characterized cohort of 203 prevalent HD patients [56% men, median age 66 (interquartile range 51–74) years, vintage time 29 (15–58) months] with a mean follow-up period of 29 (14–58) months.

Results. Median anti-PC levels were lower in HD patients with systemic collagen vascular disease (18.9 versus 45.2 U/mL, P = 0.01) and in patients who died during the follow-up period (29.5 versus 53.9 U/mL; P = 0.0008). The patients with an anti-PC value below the median (42.1 U/mL) had a higher mortality rate with a crude hazard ratio (HR) of 2.13 (95% CI 1.40–3.22). These patients remained at higher risk of death (HR 1.76; 95% CI 1.13–2.74) even after adjustment for traditional risk factors (age, sex, smoking habits, CKD aetiology, CVD and diabetes), protein-energy wasting and inflammation (HR 1.70; 95% CI 1.19–2.68).

Conclusion. Low levels of natural IgM antibodies against PC are independent predictors of death among HD patients. Further studies are needed to define the clinical role of such measurements and to explore potentials for active immunization, with PC as an antigen, or passive immunization, aiming at raising levels of protective anti-PC.

Methods. We randomized 200 elective, consecutive patients (mean age 74.9 ± 7.3 years; 65% male, 25% diabetics) with basal creatinine clearance ≤55 ml/min to receive oral N-acetylcysteine (600 mg bid the day before and the day of the procedure plus saline i.v. 0.9% 1 ml/kg/h 12–24 h before and 24 h after the procedure, n = 99) or placebo and saline at the same time intervals, n = 101. The contrast medium was non-ionic isosmolar (Iodixanol, Visipaque Amersham Health). Contrast-induced nephropathy was defined as an increase in serum creatinine >0.5 mg/dl or >25% within 3 days after the procedure. Serum creatinine was measured at baseline, 24, 48 and 72 h after the procedure.

Results. Contrast-induced nephropathy was 8/99 (8.1%) in the N-acetylcysteine group versus 6/101 (5.9%) in the placebo group, P = 0.6. No difference was noted in high-risk subgroups such as diabetics (4/25 versus 2/25 P = 0.4) and those with serum creatinine clearance <42.3 ml/min (5/54 versus 4/48; P = 0.9).

Conclusion. In our experience, N-acetylcysteine did not prevent contrast-induced nephropathy in patients receiving isosmolar (iodixanol) contrast media and adequate hydration.

Methods. The human proximal tubular epithelial cell lines HK-2 and HKC-8 were treated with reduced oxygen tension (1% O₂) or the hypoxia mimetic dimethyloxalyl glycine (DMOG). CTGF was analysed by Western blotting, real-time RT-PCR and luciferase gene expression assays.

Results. Exposure of HK-2 or HKC-8 cells to hypoxia or treatment with DMOG for up to 24 h reduced cellular as well as secreted CTGF protein synthesis. Downregulation was also detectable at the mRNA level and was confirmed by reporter gene assays. Hypoxic repression of CTGF synthesis was dependent on HIF-1, as shown by HIF-1 knockdown by siRNA. Furthermore, exposure to hypoxia reduced CTGF synthesis in response to TGF-β. A negative correlation between HIF-1 accumulation and CTGF synthesis was also observed in renal cell carcinoma cells (RCC4 and RCC10). Reexpression of von Hippel-Lindau protein reduced HIF-1 and increased CTGF synthesis.

Conclusions. We provide evidence that hypoxia inhibits CTGF synthesis in human proximal tubular epithelial cells, involving HIF-1. Under hypoxic conditions, induction of CTGF by TGF-β was repressed. The reduced synthesis of the profibrotic factor CTGF may contribute to a potential protective effect of hypoxic preconditioning in acute renal injury.

Methods. Seven healthy volunteers first received HS and then IS (both 3.85 mmol sodium/kg). To investigate the role of calcium metabolism, four patients received HS, two with an activating mutation (ADH) and two with an inactivating mutation (FHH) of the calcium-sensing receptor (CaSR).

Results. In healthy volunteers, HS produced mild hypernatraemia, a 4-fold rise in vasopressin (to 2.2 ± 0.85 pg/mL) and a 3-fold rise in natriuresis compared with a 1.5-fold rise with IS (P = 0.002). This confirmed osmomediated natriuresis. HS caused calciuresis to increase 1.4-fold and then reduced it 1.4-fold, whereas IS failed to increase calciuresis and caused it to fall 3.7-fold (P = 0.05). Natriuresis and calciuresis in ADH patients were similar to healthy volunteers receiving HS, whereas a blunted response was seen in FHH patients. Patient vasopressin levels did not exceed 1.3 pg/mL and changes from baseline were variable. In one FHH patient, a 3-fold rise in vasopressin did not prevent the blunted natriuresis and calciuresis. In one ADH patient, natriuresis and calciuresis were similar to healthy volunteers despite a 1.7-fold fall in vasopressin.

Conclusions. Our data suggest that not only vasopressin (possibly via its V1a receptor), but also the CaSR (which is sensitive to high sodium concentrations) may play a role in osmomediated natriuresis. These results shed new light on osmomediated natriuresis and suggest roles for the CaSR beyond calcium regulation.

Methods. PINP, CTX, TRACP5b and BALP isoforms were analysed in serum from 46 patients within CKD stages 3–5. BMD was determined by dual-energy x-ray absorptiometry.

Results. PINP, TRACP5b and the BALP isoforms, B/I, B1 and B2, were independent predictors of total hip BMD in all patients. Furthermore, B/I predicted osteopaenia in the hip and in the distal 1/3 of the radius in CKD stage 3. The B1x isoform was detected in nine patients (20%), who had lower GFR, higher phosphate and calcium x phosphate product.

Conclusion. We found an association of BALP isoforms and other markers of bone turnover with total hip BMD, which predominantly comprises trabecular bone. The association of the new BALP isoform B1x with risk factors for vascular calcification leads us to hypothesize a possible role for B1x in this process. The significance of the BALP isoforms in CKD remains to be further explored in experimental and clinical settings in conjunction with bone histomorphometry.

Methods. Twenty-five peritoneal tissues from eight patients at initiation of PD, five long-term PD (>6 years) patients with severe peritonitis lasting for almost 1 month, nine patients after long-term PD (>6 years) without peritonitis and three normal subjects were included in the present study. Expressions of decorin, versican, hyaluronan, MMP-2, alfa smooth muscle actin (SMA) and CD68 for macrophages in these specimens were examined by immunohistochemical staining.

Results. Although expression of decorin was detected in normal subjects, it was markedly decreased with long-term PD treatment. In long-term PD patients, the expression of versican was observed in their fibrotic-thickened peritoneum. Versican was present in fibrous regions, elastic lamina of the peritoneum, vascular walls and perivascular regions. Hyaluronan was observed in the whole thickened peritoneum, but its distribution differed in part from that of versican. MMP-2 was mainly observed around the blood vessels. Alfa SMA-positive cells, namely ‘myofibroblasts’ and CD68-positive cells, i.e. macrophages, were observed in the fibrotic–thickened peritoneum of long-term PD patients. Expressions of MMP-2, hyaluronan, SMA and CD68 in the peritoneum were marked in long-term PD patients’ samples, which were strongly immunostained by versican, and were especially high in peritonitis patients.

Conclusions. It appears that alterations in PGs, including marked induction of versican with peritonitis and disappearance of decorin, are involved in peritoneal remodelling in PD patients. Versican expression was closely related to the appearance of myofibroblasts and macrophages. These observations suggest that the alteration in PG components following PD therapy and severe inflammation contribute to fibrous thickening of the peritoneum.

Results. Structural and functional cardiac abnormalities were observed in patients on maintenance dialysis. Increased left ventricular mass index (LVMI, P = 0.000), relative wall thickness (P = 0.000), myocardial performance index (MPI, P = 0.000) were documented in the patients. Lipoprotein (a) (P = 0.000), homocysteine (P = 0.001), HS-CRP (P = 0.000) and CIMT (P = 0.000) were significantly elevated in the patients. Left ventricular hypertrophy (LVH) was prevalent in 68% of the patients. Patients with LVH had higher levels of HS-CRP (P = 0.001) and CIMT (P = 0.028) than those without LVH. Haemoglobin was an independent predictor of LVMI (β: –8.9, P = 0.001), while residual diuresis and CIMT were independent predictors of diastolic dysfunction (β: –0.45, P = 0.034 and β: 5.90, P = 0.008, respectively). Albumin (β: –0.72, P = 0.018) and Kt/V urea (β: –0.48, P = 0.012) were significant predictors of CIMT. There were positive correlations between LVMI and CIMT. HS-CRP was positively correlated with LVMI as well as CIMT.

Conclusions. Elevated levels of atherosclerotic/ inflammatory risk factors, low haemoglobin levels and loss of residual renal function and their negative effects on heart are of remarkable importance in paediatric patients on maintenance peritoneal dialysis. Achieving recommended targets for haemoglobin, blood pressure and Kt/V urea, preserving residual renal function as well as managing inflammation and subsequent arteriosclerosis is obviously essential to improve the patients’ prognosis.

Methods. Two hundred and thirty-three HD patients were recruited, including 120 with type 2 diabetes. Abdominal fat distribution was evaluated by computed tomography (CT) scans. Systemic atherosclerosis was assessed by intima–media thickness (IMT) using high-resolution B-mode ultrasonography. The insulin resistance was estimated by the homeostasis model assessment-insulin resistance (HOMA-IR).

Results. Spearman's analysis revealed that both VFA and SFA showed a significant relationship with HOMA-IR and also that SFA was correlated significantly with IMT in all HD patients. SFA was an independent risk factor associated with HOMA-IR and IMT in multiple regression analysis. Neither body mass index (BMI) nor VFA was a predominant determinant of HOMA-IR and IMT. IMT in HD patients with high SFA/low BMI groups was significantly higher than in the low SFA/high BMI groups.

Conclusion. It appears that there is a close relationship between SFA and insulin resistance or atherosclerosis in HD patients. It was suggested that SFA plays important roles related to carbohydrate or lipid metabolism in HD patients.

Methods. Data were collected and recorded from all written referrals from primary care between 1 April 2004 and 31 March 2008. Referral patterns for each postcode sector were mapped using Microsoft MapPoint 2004. The effect of chance on referral patterns was modelled by using small area analysis techniques. The association between the CKD prevalence reported from QOF data and the estimated CKD prevalence was examined at post-code district level.

Results. There were 1461 referrals in 2 years prior to the introduction of the initiatives and 2890 referrals in the 2 years post-introduction. The main reason for referral in both groups was impaired renal function or previously established renal disease. Reported comorbidity was similar between the groups. Mapping showed that there was wide heterogeneity in referral behaviour in the first 2 years of the study, which was less in the second period. Small area analysis suggested that the variation that led to the extremal quotients observed in both of the study periods was not due to random variation in referral pattern alone. There was no correlation between the reported CKD prevalence and the referral rates.

Conclusion. Referral patterns have changed between 1 April 2004 and 31 March 2008. The main findings were an increase in referral rate and in the age at referral without a significant change in reported comorbidity of the people referred. The main increase in referral rates was seen in more advanced CKD suggesting more targeted referral of patients with CKD to renal services.

Methods. Excluding the patients fully qualified for systemic lupus erythematosus (SLE) diagnostic criteria, we recruited 36 cases having a renal biopsy featured with histopathology of primary idiopathic MN but ultrastructural appearance of TRIs in glomerular endothelial cells (GECs). We investigated their clinical and pathological profiles and focused on the potential connections with the underlying diseases and treatment outcomes.

Results. One-third of our cases showed no identifiable underlying aetiology. Other underlying disease groups included autoimmune disease (25%), hepatitis (14.7%), potential Helicobacter pylori infection (13%), diabetes (5.6%) and lymphoma (5.6%). Pathologically, patients in the autoimmune group tended to have more heterogeneous membranous deposits with frequent mesangial and subendothelial deposits. While all patients of the autoimmune group presented complement C1q in glomeruli, more than two-thirds of the patients in others groups were negative for C1q. Clinically, the patients in autoimmune and hepatitis groups were younger in age and had less remission of proteinuria following treatment, while the other groups of patients achieved partial or complete remission more frequently.

Conclusion. The underlying diseases of our patients were consistent with the major disease categories that have been frequently linked to secondary MN. The HP group was more akin to undefined groups regarding their pathological and clinical profiles. Since the MN in the undefined group might be the only renal manifestation antedating other clinical presentations of the corresponding underlying disease, a long-term follow-up and meticulous search for aetiological factors are required to validate this assumption.

Methods. Sixty-three IgAN patients were enrolled, where 32 first-degree relatives of 19 patients and 44 spouses of 44 patients were recruited. Healthy blood donors (n = 39) were used as normal controls. Biotinylated HAA (Helix aspersa) was utilized to detect the Gal-deficient IgA1 in enzyme-linked immunosorbent assay (ELISA). All the results were corrected by serum IgA1 concentration.

Results. Compared with normal controls, the sera IgA1 of patients and their first-degree relatives demonstrated increased Gal-deficient IgAl level (0.17 ± 0.09 versus 0.10 ± 0.04, P = 0.001; 0.14 ± 0.07 versus 0.10 ± 0.04, P = 0.028); no significant difference between patients and their first-degree relatives was detected (0.17 ± 0.09 versus 0.14 ± 0.07, P = 0.127). In contrast, serum Gal-deficient IgA1 level of IgAN patients was higher than their counterpart spouses and normal controls (0.18 ± 0.13 versus 0.14 ± 0.09, P = 0.009; 0.18 ± 0.13 versus 0.10 ± 0.04, P = 0.001), while that of patients’ spouses was comparable with normal controls (0.14 ± 0.09 versus 0.10 ± 0.04, P = 0.075). There was no correlation between clinicopathological data and serum Gal-deficient IgA1 level.

Conclusion. The patients with IgAN and their first relatives showed significant higher Gal-deficient IgA1 level than healthy controls, whereas patients' spouses were the same as healthy controls. It can be suggested that the Gal-deficient IgA1 might be inherited in Chinese patients with IgAN.

Methods. The study involved 44 patients with CKD stages 2–3; 27 of them were treated with cholecalciferol (5000 IU/week) for 12 months. [Ca²⁺]_i was measured using Fluo-3 AM fluorimetry. Intracellular calcium reserves were emptied by the application of thapsigargin (Tg), a specific inhibitor of endoplasmic reticulum Ca²⁺-ATPase. 2-Aminoethyl-diphenyl borate (2APB) was used to examine the capacitative calcium entry.

Results. [Ca²⁺]_i of CKD patients was substantially higher in comparison with healthy subjects: 123 (115–127) versus 102 (98–103) nmol/l, P < 0.001. The calcium concentration of Tg-sensitive stores and the capacitative calcium entry were also significantly increased in CKD patients. After the 12-month vitamin D₃ supplementation, there was a marked decrease in [Ca²⁺]_i [105 (103–112) nmol/l, P < 0.001 versus baseline], independently of the increase in 25(OH)D₃ or the decrease in PTH levels. No significant changes in intracellular calcium reserves and the capacitative calcium entry were found.

Conclusions. Our results demonstrate that (1) [Ca²⁺]_i, intracellular calcium stores and the capacitative calcium entry were significantly increased already in early stages of CKD; (2) long-term vitamin D₃ supplementation normalized [Ca²⁺]_i without any effect on intracellular calcium reserves or the capacitative calcium entry.

Methods. In a prospective, observational study, 70 consecutive CKD patients, stage 5, were screened and 30 patients were selected and followed up monthly, for 24 months or until the start of RRT, set at an eGFR = 6.0 ml/min/ 1.73 m² or at the occurrence of pre-defined urgent criteria. The SF-36 questionnaire to evaluate the QoL was performed at the first and the last visit.

Results. The median time to the start of dialysis was 11.8 (25th and 75th: 5.5–17.3) months. Only seven patients urgently started dialysis, after 8 months (25th and 75th: 4.8–20). The mean monthly cost of care was 1146 ± 917 per patient. The QoL was similar to that of the general population and did not change at the last assessment.

Discussion. This is the first study evaluating the economic impact of intensive conservative management of CKD stage 5 to postpone start of dialysis in tertiary care. This strategy allows us to safely gain a significant amount of time free from dialysis, with good QoL and major savings in the costs of nation's dialysis budget. The present results, however, are applicable only to low comorbidity patients referred to nephrology care and may not be generalized to all patients starting RRT.

Method. A total of 25 patients were randomized to sirolimus 2 mg/day and 25 patients to no treatment except standard care. Treatment adherence was monitored electronically. At baseline and at Month 6, laboratory parameters were analysed and the urinary protein profile in 24-h urine collections was determined.

Results. Both treatment groups were well balanced for age, sex and renal function. In 94.1 ± 11.4% of the study days, patients in the sirolimus group were exposed to the drug when assuming a therapeutic efficacy duration of 30 h. At Month 6, the mean sirolimus dose and trough level were 1.28 ± 0.71 mg/day and 3.8 ± 1.9 µg/l, respectively. Glomerular (albumin, transferrin, IgG) and tubular (retinol-binding protein, ₁-microglobulin) protein excretion remained unchanged. Glomerular filtration rate also did not change significantly. Haematological parameters were similar in both groups, except for a mild reduction of the mean corpuscular volume of erythrocytes in patients receiving sirolimus. Lipid levels were similar in both groups. Adverse events were transient and mild, and no grade 3 or 4 events occurred. The incidence of infections was similar in the sirolimus group (80%) and the standard group (88%). The most common gastrointestinal adverse events were mucositis (72% in the sirolimus group versus 16% in the standard group, P = 0.0001) and diarrhoea (36% in the sirolimus versus 20% in the standard group, P = 0.345).

Conclusion. Treatment of ADPKD patients with sirolimus with a dose of 1–2 mg/day is safe and does not cause proteinuria or impairment of GFR. Treatment adherence was excellent. (ClinicalTrials.gov number, NCT00346918.)

Methods. The cohort was further followed up until 2005 in 97 clinical units in Japan. The data from 2283 patients were analysed by Cox regression to determine the predictors of ESRD in IgAN, and their β-coefficients were converted into scores to estimate ESRD risk within 10 years.

Results. During the follow-up (median, 87 months), 252 patients developed ESRD. Male sex, age less than 30 years, family histories of chronic renal failure and chronic glomerulonephritis, hypertension, proteinuria, mild haematuria, hypoalbuminaemia, low glomerular filtration rate and a high histological grade at initial renal biopsy were associated with the risk of ESRD in the multivariable analysis. A scoring system was framed to estimate the 10-year ESRD risk using eight variables significant in both univariable and multivariable models. This prognostic score accurately classified patients by risk: patients with estimates of 0–4.9, 5.0–19.9, 20.0–49.9 and 50.0–100% had an observed incidence of 1.7, 8.3, 36.7 and 85.5%, respectively. The corresponding area under the receiver-operating characteristic curve was 0.942 (95% confidence interval, 0.925–0.958).

Conclusion. This validated scoring system to quantitatively estimate ESRD risk during the 10-year follow-up of IgAN patients will serve as a useful prognostic tool in clinical practice.

Methods. Patients who were on chronic intermittent haemodialysis were assessed for sublingual microvascular flow by SDF imaging pre- and post-TP, performed before and after ultrafiltration (UF). Sublingual microvascular flow was estimated using a semi-quantitative microvascular flow index (MFI) in small (diameter <25 µm, which includes capillaries), medium (25–50 µm) and large-sized (50–100 µm) microvessels (no flow: 0, intermittent flow: 1, sluggish flow: 2 and continuous flow: 3). Changes were evaluated with the non-parametric paired Wilcoxon test. P < 0.05 was judged to indicate a significant difference.

Results. Thirty-nine adult patients took part in the study. The underlying diseases causing ESKD were predominantly hypertension (HT, n = 10), diabetes mellitus (DM, n = 7) or both (n = 3). At the start of UF, microvascular flow did not change significantly by TP. After completion of UF, MFI had decreased significantly in all types of microvessels (P < 0.001). After UF (median volume extraction 2.49l), MFI was lower than that at the start of UF and increased in most patients after TP (P < 0.001) in all categories of vessels. Changes were most prominent in the smallest microvessels.

Conclusions. Sublingual microvascular perfusion is reduced by UF and can be restored temporarily using autotransfusion by TP due to increased venous return. SDF imaging is able to detect these volume changes. SDF imaging and TP could become a useful bedside tool to evaluate the patient's (microvascular) volume status and response to therapy in dialysis or intradialytic hypotension.

Methods. In the present study, potential patient- and treatment-related determinants of convective volume were analysed in 235 consecutive patients on post-dilution HDF using multivariable linear regression models. All patients (age 64 ± 14 years; 61% male) participated in the ongoing CONvective TRAnsport STudy (CONTRAST). Additionally, differences in convective volumes between dialysers were evaluated.

Results. The mean convective volume was 19.4 ± 4.0 L (±SD) per treatment, with a large variation between the participating centres (centre means ranging from 13.4 ± 0.9 L to 24.5 ± 0.12 L, ± SE). The mean filtration fraction of the blood flow was 25.9 ± 3.6. In the multivariable analysis, factors that were significantly related to convective volume were haematocrit [inversely, regression coefficient (B) = –1.4 ± 0.4 L per 10%], serum albumin (positively, B = 1.0 ± 0.4 L per 10 g/L), blood flow rate (positively, B = 0.4 ± 0.04 L per 10 mL/min) and treatment time (positively, B = 5.1 ± 0.4 L/h). In addition, significant differences between dialysers were observed, likely explained by different operational conditions.

Conclusions.  Apart from increasing the treatment time and blood flow rate, convective volumes could be optimized by increasing the filtration fraction in each individual, provided that transmembrane pressures are well within safe limits. The precise role of dialyser characteristics on maximal achievable convective volumes in clinical practice is a topic for further research.

Methods. Renal registries participating in the ERA–EDTA Registry were asked to provide data on serum creatinine recorded 0–4 weeks before the start of dialysis in incident dialysis patients in 1999 and 2003. Within this cohort study, data were available in 11 472 patients from nine national or regional European renal registries. Cox regression analyses were performed to examine the association between GFR estimated by the four-variable MDRD equation (eGFR) and all-cause mortality, using a follow-up through 31 December 2005.

Results. In the 2003 data, the mean eGFR was 8.6 ml/min/1.73 m². The unadjusted survival analyses showed that an increase in eGFR of 1 ml/min/1.73 m² was associated with a higher mortality risk (HR = 1.03; 95% CI: 1.03–1.04) that remained similar after adjustment for age, gender, primary renal disease, treatment modality, country and comorbidity. The findings were consistent across gender, treatment modalities, geographical regions and time periods (2003 versus 1999), but the association between a higher eGFR at the start of dialysis and mortality was the strongest in the youngest age groups and in patients with glomerulonephritis. Analyses at centre level showed that a 10% increase in the percentage of patients starting dialysis at high eGFR levels (≥10.5 ml/min) was associated with a 22% higher mortality risk (HR = 1.22; 95% CI: 1.18–1.26).

Conclusions. This European study showed that a higher eGFR at the start of dialysis was associated with a higher mortality risk. However, an answer to the question when to start dialysis needs to come from randomized controlled trials.

Methods. Cell-derived microparticles, markers for coagulation activation (F₁₊₂, TAT, sTF, sEPCR), fibrinolysis (d-dimer, tPA, ₂-AP), platelet activation (β-TG, PF4), endothelial activation (vWF) and acute phase response (IL-6, CRP) were studied in relation to renal function and severity of the disease and compared to data from 36 age- and sex-matched healthy controls (17 males).

Results. Markers for endothelial activation and fibrinolysis were normal. Male patients had elevated levels of sTF and β-TG, with an association between sTF and renal function and severity of the disease. In female patients, levels of TAT, β-TG, PF4, CD63-positive platelet-derived microparticles and IL-6 were somewhat increased, with no correlation with renal function or disease severity.

Conclusions. Only minimal abnormalities in markers for platelet, endothelial activation and coagulation activation and fibrinolysis could be established in a large cohort of Fabry disease patients. The existing laboratory abnormalities are more likely related to renal insufficiency rather than to Fabry disease itself.

Methods. Osteocalcin, adiponectin and leptin were prospectively measured in a cohort of 61 CKD patients. A new non-invasive 3D bone imaging technique was performed (high-resolution peripheral quantitative computed tomography, HR-pQCT), measuring volumetric BMD (vBMD) and microarchitecture parameters at the distal tibia.

Results. Patients’ mean age was 67.2 ± 13.9 years and mean GFR 33 ± 12 mL/min/1.73 m². We found a positive association between serum osteocalcin and adiponectin (r = 0.29, P = 0.021). Univariate analysis showed inverse correlations between serum adiponectin and total vBMD (r = –0.33, P = 0.01), cortical thickness (r = –0.34, P = 0.008) and trabecular vBMD (r = –0.27, P = 0.04). These associations remained significant in multivariate analysis between serum adiponectin and total vBMD, cortical vBMD and cortical thickness.

Conclusion. We report for the first time an inverse relationship between bone density and adiponectin, as well as a positive association between osteocalcin and adiponectin in CKD II–IV patients.

Methods. We describe our experience with 25 patients aged 71.2 ± 7.5 years with a previous history of HD for 55.4 ± 54 months, dialysed with IPD for more than 3 months. IPD was performed three times weekly for 8–10 h.

Results. Mean values for haematocrit, serum urea, creatinine, sodium, potassium and calcium were comparable with other ESRD populations, whereas there were significantly lower values for albumin (3.2 ± 0.3 mg/dL) and significantly higher values for phosphorus (7.1 ± 1.7 mg/dL) despite the use of phosphate binders. The patients survived for a mean of 16.8 ± 11.5 (3–43) months despite very low solute clearances, as expressed by Kt/V urea (1 ± 0.26) and weekly creatinine clearance (27.2 ± 7.6 L/week). However, by using 22.9 ± 4.5 L of various combinations of isotonic and hypertonic PD fluids, the mean ultrafiltrate was 1854 ± 326 mL per session. There were only two cases of peritonitis, unrelated to IPD per se.

Conclusions. Considering the underlying comorbidities, IPD remains a valuable and effective option with acceptable survival rates, for a special population of ESRD patients not able for various reasons to undergo HD, neither PD at home.

Method. Thirty-one stage-5 CKD patients underwent haemodynamic assessment prior to and 3 months after creation of AVF. Haemodynamic assessment included measurement of blood pressure (BP), central and carotidal pulse wave profile analysis, and carotido-femoral and carotido-radial pulse wave velocities (PWV). Pre-AVF and post-AVF haemodynamic parameters were compared using the Wilcoxon signed-rank test or the paired Student t-test as appropriate. Pearson correlations, single and multiple linear regressions, were used to determine the association between variables.

Results. After creation of AVF, peripheral and central BPs decreased without significant change in heart rate (HR) or pulse pressure. Carotido-femoral PWV (_c-fPWV) fell from 13.2 ± 4.1 to 11.7 ± 3.1 m/s (P < 0.001). There was an increase in the central augmentation index (20.8% ± 11.5 versus 23.7% ± 11.6, P = 0.07) of borderline significance, and a significant reduction in the subendocardial viability ratio (153% ± 34 versus 143% ± 32, P < 0.05), which was mainly the result of a decrease in the diastolic pressure time index (DPTI) without any significant change in the diastolic duration. The reduction of _c-fPWV was explained by changes in mean BP and HR (R² = 0.29). The reduction in DPTI was related to changes in central diastolic BP and changes in end-systolic BP (adjusted R² = 0.87). The significant improvement in aortic stiffness was mostly the result of the relative reduction of _c-fPWV in the subgroup of patients with baseline _c-fPWV above the median value of 13 m/s.

Conclusion. The creation of AVF is associated with a passive improvement of aortic stiffness especially in patients with stiffer arteries. This improvement in arterial stiffness could potentially be beneficial to the cardiovascular system despite an associated deterioration in the aortic pulse wave profile.

Methods. We genotyped six single nucleotide polymorphisms (SNPs) for five common T2D genes including adiponectin, C1Q and collagen domain containing (ADIPOQ), ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1), growth hormone secretagogue receptor (GHSR), peroxisome proliferator-activated receptor gamma (PPAR) and transcription factor 7-like 2 (TCF7L2). There were 216 T2D patients diagnosed with DN and 178 age-similar T2D without DN (control) subjects. To investigate gene–gene interactions, we employed both generalized multifactor dimensionality reduction (GMDR) method and logistic regression models.

Results. Single-locus analyses showed significant main effects of ENPP1 (P = 0.0032; adjusted OR = 1.85; 95% CI = 1.17–2.92) on the risk of DN in T2D. Furthermore, a potential gene–gene interaction involving ENPP1 and GHSR was suggested in the best two-locus GMDR model (P = 0.021). The significant three-locus GMDR model (P < 0.001) was also identified among ADIPOQ, GHSR and TCF7L2. Analyses using logistic regression models confirmed the gene–gene interactions.

Conclusions. The results suggest that the SNPs from the T2D-related genes may contribute to the risk of DN in T2D independently and/or in an interactive manner in Taiwanese T2D patients.

Methods. We retrospectively enrolled 7028 adult incident patients who began haemodialysis between 1 January and 31 December 2002. A total of 5890 patients with mature arteriovenous fistula or arteriovenous graft, before or after beginning regular haemodialysis, were identified between 1 January 2000 and 31 December 2003. The Cox regression hazard model was used to assess the impact of sex, age, diabetes, type of access and timing of vascular access maturation on the duration of primary vascular access patency.

Results. Of the study population, 2920 patients (50%) had diabetes; 4929 patients (84%) received fistulas and 961 (16%) grafts. Grafts, female sex and advanced age were significantly associated with shorter primary vascular access patency duration (P < 0.05). Diabetes was a risk factor for shorter primary vascular access patency duration for incident patients with mature fistulas before or after initiation, but not for patients with mature graft. Arteriovenous graft placement and maturation were better when completed >6 months prior to haemodialysis initiation for the duration of primary access patency.

Conclusion. Demographic characteristics and timing of vascular access maturation affect access type and duration of primary access patency among incident patients. Individual programmes for vascular access may be necessary to establish functional long-term access.

Methods. This was a cross-sectional study performed on OLT recipients within a single liver transplant centre where creatinine (n = 41) and cystatin C (n = 30) were measured and glomerular filtration rate (GFR) estimated using the Modification of Diet and Renal Disease (MDRD), Cockcroft–Gault (CG), Hoek, Larsson, Filler and Le Bricon equations. Comparison was made with the nuclear GFR (nGFR) (n = 41) measured through 51-Cr EDTA clearance.

Results. The mean age of recipients was 56 ± 13 years, and they were 6.5 ± 4.7 years post-OLT. Fifty-six percent of recipients had a nGFR ≤60 mL/min/1.73 m². nGFR correlated significantly with all predictive equations (P < 0.001). The MDRD, CG and Le Bricon equations had the smallest degree of bias (–7.6, –7.3 and 3.4 mL/min/1.73 m², respectively), with 22%, 22% and 27% of estimates, respectively, being within 10% of nGFR measurements. In OLT recipients with nGFR ≤60 mL/min/1.73 m², the degree of bias of both the creatinine-base MDRD and cystatin-based Hoek equations was within 2 mL/min/1.73 m² difference between the measured and estimated GFR, but 41% and 36% of estimates were within 10% of the nGFR measurement.

Conclusions. Therefore, the degree of inaccuracy in cystatin C- and creatinine-based predictive equations brings into question their clinical utility in OLT recipients. We have no evidence that cystatin C is superior to creatinine in this population.

Methods. The subjects of this study were 134 PD patients who started dialysis at the Yonsei University Health System between January 2000 and December 2005. Timed urine collections were performed within 1 month of PD commencement and at 6-month intervals thereafter. The slope of decline of RRF over time was calculated by linear regression analysis of serial urinary urea and creatinine clearances for each patient. Biochemical and clinical data at the time of initial urine collection were considered as baseline.

Results. At baseline, 32.8% of the PD patients had hyperuricaemia (UA ≥7.0 mg/dl). A significant majority of patients with hyperuricaemia were diabetic (P = 0.02). Hypertensive patients had a higher UA level (P = 0.002) compared to normotensive patients. The overall reduction rate of RRF in hyperuricaemic patients was significantly higher than in the normouricaemic group (P = 0.001). In the multiple linear regression analysis, hyperuricaemia and history of DM showed a significant negative correlation with the reduction rate of RRF after adjusting for demographic data, comorbid conditions, body mass index, baseline RRF and medications (P = 0.001).

Conclusions. Hyperuricaemia is common among PD patients and is significantly associated with the rate of decline of RRF.

Methods. All CKD patients who visited the outpatient nephrology clinics at two centres of the Chang Gung Memorial Hospital in 2006–07 were enrolled. The incidence of dialysis and mortality were compared between MPE recipients and non-recipients. The content of the MPE was standardized in accordance with the NKF/DOQI guidelines. Prognostic factors for progression to end-stage renal disease (ESRD) and all-cause mortality were analysed by using the Cox proportional hazards model.

Results. Of 573 patients, 287 received MPE. Dialysis was initiated in 13.9% and 43% of the patients in the MPE and non-MPE groups, respectively (P < 0.001). The mean follow-up period was 11.7 ± 0.9 months. The overall mortality was 1.7% and 10.1% in the MPE and non-MPE groups, respectively (P < 0.001). Cox regression analysis revealed that diabetes, estimated glomerular filtration rate (eGFR), high-sensitive C-reactive protein (hs-CRP) and MPE assignment were significant independent predictors for progression to ESRD. Independent prognostic factors for mortality included age, diabetes, eGFR, hs-CRP and MPE assignment.

Conclusions. MPE based on the NKF/DOQI guidelines may decrease the incidence of dialysis and reduce mortality in late-stage CKD patients.

Methods. Rat tubular cell line (NRK-52E) and mice were used as the model system. Gentamicin-induced apoptosis in renal tubular cells was examined using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling. We introduced short interfering RNA transfection and gene-deficient mice to investigate the protective mechanism of l-carnitine.

Results. We found that l-carnitine inhibited gentamicin-induced reactive oxygen species generation and correlative apoptotic pathways, resulting in the protection of NRK-52E cells from gentamicin-induced apoptosis. The treatment of l-carnitine also lessened gentamicin-induced renal tubular cell apoptosis in mice. l-carnitine was found to increase the prostacyclin (PGI₂) generation in NRK-52E cells. The siRNA transfection for PGI₂ synthase significantly reduced l-carnitine-induced PGI₂ and l-carnitine's protective effect. We found that the activity of the potential PGI₂ nuclear receptor, peroxisome proliferator-activated receptor alpha (PPAR), was elevated by l-carnitine treatment. The siRNA-mediated blockage of PPAR considerably reduced the anti-apoptotic effect of l-carnitine. In PPAR-deficient mice, l-carnitine treatment also lost the inhibitory effect on gentamicin-induced apoptosis in kidneys.

Conclusions. Based on these findings, we suggest that l-carnitine protects renal tubular cells from gentamicin-induced apoptosis through PGI₂-mediated PPAR activation.

Methods. A total of 134 subjects [60 haemodialysis (HD), 28 peritoneal dialysis (PD) and 46 CKD stage 4] were studied. All survivors completed 40 months of follow-up. VC was measured using multi-slice spiral CT of the superficial femoral artery. Circulating osteoprotegerin (OPG), Fetuin-A and high sensitivity C-reactive protein (hs-CRP) were measured in addition to standard clinical biochemical analysis.

Results. After a 40-month follow-up, 31 patients had died (27 men and 4 women). Of 31 subjects, 31 had evidence of significant VC. The majority of deaths were in the HD group (48%), 36% were PD subjects and 16% were CKD subjects. The outcome of interest was survival at the end of follow-up. Multivariate logistical regression analysis revealed male gender [OR 8.06 (1.34–48.450) P = 0.02], OPG >25 pmol/L [OR 5.31(1.35–20.88) P = 0.02] and hypoalbuminaemia [OR 0.26 (0.12–0.56) P < 0.01], were associated with increased odds of death.

Conclusion. We have previously reported that VC and low albumin predict death in CKD stages 4 and 5 over a 2-year follow-up period. These data show that OPG, independent of CRP, is also associated with a negative outcome. The mechanisms remain to be elucidated; however, it is likely that they are associated with vascular damage through mechanisms in addition to VC.

Methods. All 1844 adult native kidney biopsies for 30 years (1976–2005 inclusive) were analysed. The data were divided into three 10-year time frames, and trends in the biopsy rate and diagnosis of primary glomerular disease were considered.

Results. Biopsy rates increased significantly from 2.02 to 7.08 per hundred thousand population per year (php/year) (² = 55.9, P < 0.001), and the mean patient age at biopsy rose from 33 to 49 years over the study period (F = 58, P < 0.001). Primary GN was documented in 49% of biopsies; the most common diagnoses within this group were IgA nephropathy (38.8%), membranous nephropathy (29.4%), minimal change disease (9.8%), membranoproliferative GN type 1 (9.6%) and FSGS (5.7%). There was a significant increase in the proportion of IgA nephropathy (² = 9.6, P = 0.008) and a decrease in membranous nephropathy (² = 7.2, P = 0.03) over time. The population incidence of FSGS was low and unchanged at 0.18 php/ year from 1986 to 2005.

Conclusions. Consistent with several other European studies, IgA nephropathy was the most common primary glomerular disease in this UK region. The diagnosis of FSGS was uncommon with no evidence of a rise in incidence.

Methods. Thirty-seven patients from two haemodialysis units in Winnipeg, Manitoba, Canada, were recruited, and 17 patients were treated with thrice weekly warfarin and compared to 20 patients treated with daily warfarin therapy. The patients were followed for 1 year with weekly international normalized ratio (INR), dosage and adverse events recorded. The primary outcome was percentage of time with INR in target and sub (<1.5)- and supra (>4)-therapeutic INR. Adverse events were recorded in the two groups.

Results. The thrice weekly group had a higher burden of comorbidity (Charlson comorbidity index of 6.35 ± 1.77 versus 4.55 ± 1.64, P = 0.003) compared to the daily dosage group. In the thrice weekly dosage group, time within target INR was higher (56.9 versus 49.3%, P = 0.008), and time with supra-therapeutic INR > 4 lower (2.7 versus 4.3%, P = 0.03). Total bleeding events (7 versus 6) and major bleeding events (3 versus 2 events) were similar between the two groups.

Conclusion. In this pilot study, thrice weekly warfarin appears to be a safe and feasible dosing strategy in a select patient population. A randomized controlled trial of thrice weekly warfarin is warranted.

Methods. A total of 3679 participants of the Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg (INVADE) composed the community-based cohort study. Measures of renal function were estimated using the Cockcroft–Gault equation and divided into normal, mild and moderate-to-severe impaired renal function (creatinine clearance ≥60, 45–59 and <45 mL/min/1.73 m², respectively). The main outcome measures were cognitive impairment at baseline and new cognitive impairment after a 2-year follow-up. Cognitive function was measured using the 6-Item Cognitive Impairment Test (6CIT). Multiple logistic regression analysis was used to assess the association between renal function and cognitive impairment.

Results. At baseline, 396 participants (10.8%) had cognitive impairment. After the 2-year follow-up, 194 participants (6.2%) developed new cognitive impairment. The incidence of cognitive impairment across the groups with normal renal function, mild and moderate-to-severe kidney disease at baseline were 5.8, 9.9 and 21.5%, respectively. Multiple logistic regression analysis after adjustment for possible confounders including traditional cardiovascular risk factors showed a significant association for participants with moderate-to-severe kidney disease at baseline to develop new cognitive impairment after the 2-year follow-up [odds ratio: 2.14 (95% confidence interval: 1.18–3.87), P = 0.01].

Conclusions. In summary, moderate-to-severe impaired renal function is associated with incident cognitive impairment after 2 years in a large cohort of elderly subjects.

Methods. We analysed data from 1255 diabetic haemodialysis patients, participating in the German Diabetes and Dialysis Study between 1998 and 2004. The patients were stratified by the presence or absence of wasting (albumin ≤3.8 versus albumin >3.8 g/dL; BMI ≤23 versus BMI >23 kg/m²). Using Cox regression analyses, we calculated the risks of (1) all-cause mortality and (2) CVE according to baseline PTH levels. All analyses were adjusted for age, sex, atorvastatin treatment, duration of dialysis, comorbidity, HbA1c, phosphate, calcium, blood pressure, haemoglobin and C-reactive protein.

Results. Patients had a mean age of 66 ± 8 years, and 54% were male. Among patients without wasting (albumin >3.8 g/dL, n = 586), the risks of death and CVE during 4 years of follow-up significantly increased by 23% and 20% per unit increase in logPTH. Patients in the highest PTH tertile had a 74% higher risk of death (HR_adj 1.74, 95% CI 1.27–2.40) and a 49% higher risk of CVE (HR_adj 1.49, 95% CI 1.05–2.11) compared to patients in the lowest PTH tertile. In contrast, no effect was found in patients with wasting. Accordingly, additional analyses in strata of BMI showed that PTH significantly impacted on death and CVE [HR(logPTH)_adj 1.15 and 1.14, respectively] only in patients without, but not in patients with, wasting.

Conclusions. Wasting modifies the association of PTH with adverse outcomes in diabetic dialysis patients. High PTH levels are of concern in the patients without wasting, while the effect of PTH on mortality is nullified in the patients with wasting.

Methods. These assays were applied to examine the anti-fibrotic activities of 21 compounds isolated from plants used in Chinese medicine and methanol extracts of 12 Chinese herbs. Lactate dehydrogenase release assay and cell detachment index were used to monitor cytotoxicity. Changes in fibrogenic molecular markers were observed by reverse transcriptase quantitative polymerase chain reaction and high-content imaging analysis of immunofluorescence.

Results. Three flavonoids (quercetin, baicalein and baicalin) and two non-flavonoids (salvianolic acid B and emodin) demonstrated anti-fibrotic activities in both total collagen accumulation and nodule formation assays. The remaining 16 compounds had little anti-fibrotic effect or were cytotoxic. The anti-fibrotic compounds suppressed collagen I expression at both mRNA and protein levels and also variably suppressed -smooth muscle actin expression and bromodeoxyuridine incorporation. Methanol extracts of Scutellaria baicalensis Georgi, Salvia miltiorrhiza Bunge and Rheum palmatum L., which are rich sources of baicalein, baicalin, salvianolic acid B and emodin, respectively, also showed in vitro anti-fibrotic activities.

Conclusions. Five herbal compounds and three herbal extracts have in vitro anti-fibrotic activities. These data warrant further studies on these anti-fibrotic entities and suggest it a promising strategy to discover new anti-fibrotic drugs by screening more plant materials.

Methods. Reporter podocytes were treated with agonists and/or antagonists of RAR, RXR or VDR, and activities of the nephrin gene promoter, the retinoic acid response element (RARE) and the vitamin D response element (VDRE) were evaluated.

Results. Expression of nephrin in podocytes was up-regulated by ATRA and 1,25(OH)₂D₃. The nephrin gene promoter was also activated by these agents, which was mediated by RAR and VDR, but unexpectedly, not by RXR. ATRA-triggered, RAR-mediated activation of the nephrin gene promoter was not suppressed by the VDR antagonist. Similarly, ATRA-induced activation of RARE was not inhibited by the VDR antagonist. In contrast, the 1,25(OH)₂D₃-triggered, VDR-mediated activation of the nephrin gene promoter was significantly suppressed by the RAR antagonist, but not by RXR antagonists. Interestingly, 1,25(OH)₂D₃-induced activation of VDRE was not inhibited by the RAR antagonist.

Conclusions. These results suggested selective cooperation of RAR and VDR in the regulation of the nephrin gene, i.e. (1) ATRA induces nephrin gene expression via RAR independently of RXR and VDR and (2) 1,25(OH)₂D₃ induces nephrin gene expression via selective cooperation of RAR and VDR, which is independent of RXR.

Methods. C57BL/6 mice were given cisplatin (20 mg/kg) with or without -LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of -LA on NF-B activity was evaluated by examining nuclear translocation and phosphorylation of NF-B p65 subunits in kidney tissue.

Results. Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by -LA treatment. -LA decreased the tissue levels of tumour necrosis factor-, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. -LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- B p65 subunits in kidney tissue.

Conclusions. These results suggest that -LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-B activity.

Methods. In a prospective study of 100 adult cardiac surgery patients, we assessed the value of postoperative plasma NGAL in predicting AKI according to the degree of severity used for its definition.

Results. The predictive value of plasma NGAL varied according to the AKI definition used and was higher for more severe AKI (increase in creatinine >50%: mean AUC–ROC 0.79 ± 0.01) compared to less severe AKI (>25%: mean AUC–ROC 0.65 ± 0.02); P = 0.001. The discriminatory ability of NGAL for AKI also increased with increasing RIFLE classes (AUC–ROC R: 0.72, I: 0.79, F: 0.80) or AKIN stages (AUC–ROC 1: 0.75, 2: 0.78, 3: 0.81); P = 0.015. It was highest for the prediction of renal replacement therapy (AUC–ROC: 0.83).

Conclusions. In adult cardiac surgery patients, the predictive value of NGAL increases with grade of AKI. This observation needs to be taken into account when interpreting any future studies of this biomarker.

Methods. Data from all female non-immunized renal transplant candidates who received a random PTF (rPTF) (n = 620), matched PTF (mPTF) (one HLA-A and B and one HLA-DR match) (n = 86) or donor-specific blood transfusion (DST) (n = 100) between 1996 and 2006 were collected. Complement-dependent cytoxicity was used to detect anti-HLA antibodies. Sensitization and transplantation outcomes after a PTF were analyzed. Non-immunized female renal transplant recipients who did not receive a PTF were used as the control group.

Results. In 165 patients, anti-HLA antibodies (IgG) were detected after the PTF. Both historical and primary sensitizations were found. A DST induced donor-specific anti-HLA antibodies in 25% of the DST recipients. Our policy did not improve transplantation outcome in recipients of a kidney from a deceased donor (n = 368) or in recipients of a living donor [DST (n = 49) and mPTF (n = 66)].

Conclusions. A PTF did elucidate historical sensitization but induce primary sensitization as well. No beneficial effect of PTFs on transplantation outcome was found, and PTFs with the intention to detect historical sensitization are therefore not suggested.

Methods. Male C57BL/6J mice aged 19–22 months were purchased from four different suppliers. Baseline renal parameters were evaluated by measuring serum urea, serum creatinine and proteinuria. Renal morphology was analysed by quantifying glomerulosclerosis, interstitial fibrosis and amyloid deposits on paraffin sections stained with PAS, Masson trichrome, Sirius red and Congo red.

Results. We found normal renal ageing in mice from three sources, but an unexpected renal pathology in mice from one major European supplier. Mice from this supplier had significantly elevated serum urea, creatinine values and an increased urinary protein excretion. Corresponding kidneys displayed massive glomerulosclerosis with evidence of amyloid deposits and increased interstitial fibrosis.

Conclusions. Supplier-dependent differences, such as observed here, can explain irreproducibility of experimental results in renal ageing research. This can be avoided by careful baseline analysis prior to in vivo experiments.

Methods. This is a prospective cohort study of 103 consecutive Japanese patients with IMN and nephrotic syndrome. Patients were treated with cyclophosphamide (50 mg/day for the first 3 months and 25 mg/day for the next 3 months) and prednisolone (30 mg/day for the first week and the dosage was gradually tapered to withdraw by 2 years). Additional therapies were allowed for initial treatment failure or relapse.

Results. With a mean observation period of 8.5 years, 90 patients (87.4%) achieved proteinuria of <1 g/day and 78 (75.7%) achieved complete remission. A total of 27 patients did not respond to initial treatment and 30 patients had relapses after remission. Of these patients, 39 received additional therapies. At the last observation, 12 patients had developed renal insufficiency (S-Cr >1.5 mg/dL) but only 2 patients had reached renal death. Multivariate analysis revealed that the duration without remission was the strongest risk factor for renal prognosis. There were 14 deaths, and 8 patients developed cancers during the observation period.

Conclusion. Treating nephrotic IMN in Japanese patients with low-dose cyclophosphamide and prednisolone is beneficial for long-term renal prognosis with relatively few adverse effects.

Methods. This retrospective study analysed the short-term outcomes of 79 diffuse proliferative lupus nephritis patients according to the RIFLE classification.

Results. A total of 46% of patients were No AKI, 23% AKI-R, 16% AKI-I and 15% AKI-F according to the maximum RIFLE class reached on the first day of admission. The percentage of progression of AKI to the more severe RIFLE class was 6% for AKI-R, 23% for AKI-I and 75% for AKI-F (P < 0.0001), and there was an increased odds ratio (OR) of progression rate with more severe RIFLE category (OR 7.7, 95% CI 2.3–25.7, P < 0.001). The recovery rate at the end of a 24-week follow-up was 100% for AKI-R, 92% for AKI-I and 33% for AKI-F (P < 0.0001). The mean time to recovery for the groups AKI-R, AKI-I and AKI-F was 4, 11 and 20 weeks, respectively (P < 0.0001). The area under the ROC curve for progression to chronic kidney disease (CKD) was 0.96 (95% CI 0.91–1.0, P < 0.001).

Conclusion. The RIFLE classification is predictive of progression and short-term prognosis of AKI in diffuse proliferative lupus nephritis.

Methods. The in vivo roles of endogenous IL-1β and its type I receptor (IL-1RI) in renal fibrosis were studied using wild-type C57BL/6 mice, IL-1β^–/– and IL-1RI^–/– mice with unilateral ureteric obstruction.

Results. After 7 days, IL-1RI^–/– mice (IL-1 and IL-1β deficient) were protected from injury and collagen accumulation. IL-1β^–/– mice demonstrated some histological protection, but no reduction in 1(1) procollagen mRNA or biochemically measured collagen accumulation. Compared with obstructed kidneys from wild-type mice, TGF-β1 mRNA was reduced in IL-1RI^–/– mice (with trends to reduced TGF-β2 and TGF-β3). Expression of a downstream TGF-β effector, connective tissue growth factor, was decreased in IL-1RI^–/– mice. IL-1RI^–/– mice exhibited less tubulointerstitial apoptosis compared with wild-type mice. Macrophage infiltration and adhesion molecule mRNA expression was unchanged in IL-1β^–/– or IL-1RI^–/– mice. While TNF expression was similar to wild-type mice, IFN- expression was reduced in both IL-1β^–/– and IL-1RI^–/– mice. IL-1RI^–/– mice at 14 days showed a catch-up in fibrosis compared with wild-type mice.

Conclusion. IL-1/IL-1RI interactions are profibrotic in renal fibrosis. IL-1RI^–/– mice were more protected at an early stage, associated with changes in TGF-β and downstream mediators of fibrosis, but independent of the presence of infiltrating macrophages.

Methods. In this study, 20 severe sepsis patients were enrolled. A proteomic approach with two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry and bioinformatics methods was utilized to identify proteins with altered expression at different times in the treatment of continuous veno-venous haemofiltration (CVVH). All proteins were identified on the appearance of the 2-DE gel at the appropriate molecular size and pI and score from peptide mass fingerprinting. Protein identifications were confirmed by sequencing of the tryptic peptides and an independent database search based on the sequence. A further validation study was performed by western blot.

Results. Thirty-four protein spots expressed differentially were separated. Ten proteins were identified to be the commonly differentially expressed proteins in the treatment. Seven proteins decreased in the serum and three increased.

Conclusions. This study gives a novel overview of serum proteome alteration of severe sepsis patient in the treatment of CVVH. Potentially interesting proteins have been revealed that are different from those identified by method of traditional biology.

Methods. Using a small animal imager, fluorescence is measured over the depilated ear of a rat after the injection of FITC-S. The decay curve of fluorescence is used for the calculation of half-life and GFR. The thus obtained transcutaneous data were validated by simultaneously performed enzymatic and fluorometric measurements in plasma of both FITC-S and sinistrin.

Results. The results of enzymatic sinistrin determination versus transcutaneous half-life of FITC-S or plasma fluorescence correlated well with each other (R² > 0.90). Furthermore, Bland–Altman analyses proved a good degree of agreement of the three methods used. The measurements performed in healthy animals as well as different models of renal failure demonstrate its appropriateness in a wide range of renal function.

Conclusions. The transcutaneous method described offers a precise assessment of GFR in small animals. As neither blood and/or urine sampling nor time-consuming lab work is required, GFR can be determined immediately after the clearance procedure is finished. This method, therefore, simplifies and fastens GFR determinations in small lab animals compared to conventional bolus clearance techniques based on blood sampling. A low-cost device for the measurement of transcutaneous fluorescence intensity over time is under construction.

Methods. TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information.

Results. Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family.

Conclusions. We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Methods. Immortalized rat proximal tubular cells were exposed to the classic ER stress inducers tunicamycin or brefeldin A. Autophagy was detected mainly by immunoblot analysis of LC3, a widely used marker of autophagy, and also by immunofluorescent cytochemistry of LC3 and electron microscopy. Biological significance of the phenomenon was studied using bafilomycin A1, an inhibitor of autophagosome degradation. Signal transduction pathways following ER stress were also investigated using inhibitors of the MAPK pathway.

Results. Both ER stress inducers significantly increased LC3-II as a marker of autophagy in immunoblot analysis. Immunocytochemistry of LC3 and electron microscopy also showed activation of autophagy by ER stress. Inhibition by bafilomycin A1 showed that autophagy following ER stress fulfilled its intrinsic function, namely degradation of cytoplasmic components. Further, use of the MEK 1/2 inhibitor U0126, which inhibits ER stress-induced autophagy induction and ERK activation, showed that ERK, a MAPK family member, was necessary to the induction of autophagy.

Conclusions. For the first time, we demonstrate the induction of autophagy following ER stress in renal tubules, and clarify its mechanism. These findings serve as the foundation for further investigation into autophagy in renal diseases.

Methods. Conditionally immortalized murine podocytes were exposed to mechanical stretch and/or TGFβ1 for 48 h. Podocyte adhesion, apoptosis and 3β1 integrin expression were assessed.

Results. Stretch and TGFβ1 significantly reduced podocyte adhesion and 3β1 integrin expression, events paralleled by increased apoptosis. Blockade of β1 integrin, with a specific antibody, demonstrated a reduced podocyte adhesion indicating that β1 integrin downregulation was required for the loss of podocyte adhesion. This was linked to an increase in podocyte apoptosis. The role of apoptosis in podocyte adhesion was further investigated using caspase-3 inhibitors. Podocyte apoptosis inhibition did not affect stretch- and TGFβ1-mediated integrin downregulation and the loss of podocyte adhesion, suggesting that 3β1 integrin downregulation is sufficient to alter cell adhesion. Although stretch significantly increased podocyte TGFβ type I, II and III receptors but not podocyte TGFβ1 secretion, the combination of stretch and TGFβ1 did not show any additive or synergistic effects on podocyte adhesion and 3β1 integrin expression.

Conclusions. These results suggest that downregulation of 3β1 integrin expression, by mechanical forces or TGFβ1, is per se sufficient to reduce podocyte adhesion. Apoptosis may represent a parallel important determinant of the podocyte loss from the GBM.

Methods. We conducted a retrospective cohort study of Medicare beneficiaries with CKD, point prevalent as of 1 January of each calendar year 1992–2004 (n = 301 000), and a concurrent group of beneficiaries without CKD (n = 15 772 039). During the entry year, we used administrative claim data to assemble a comorbidity profile for each participant. Transfusion event rates, ESA use and parenteral iron use were of primary interest.

Results. CKD patients were at least four times more likely than non-CKD patients to receive transfusions. Transfusion rates adjusted for case mix fell from 194.2 transfusions per 1000 patient-years in 1992 to 112.2 in 2004. The decline in transfusions was highest for anaemic CKD patients receiving ESAs, which were given to 0.8% of CKD patients in 1992 and to 7.5% in 2004.

Conclusions. Transfusion use in non-dialysis-dependent CKD patients has decreased considerably but continues to be common. ESA use and possibly changed attitudes towards transfusion use explain most of the reduction noted.

Methods. The study reviewed all patients in Australia and New Zealand who commenced dialysis for treatment of end-stage renal disease (ESRD) between 1963 and 2006. Dialysis modality was assigned at 90 days. A supplementary analysis was also conducted using a contemporary cohort that included data on comorbidities, smoking and eGFR at dialysis onset.

Results. During the study period, 15 912 individuals received peritoneal dialysis (PD) and 23 658 received haemodialysis (HD). Renal recovery occurred in 176 (1.1%) PD and 244 (1.0%) HD patients. Using multivariate Cox proportional hazards regression analyses, dialysis modality was not independently predictive of time to renal recovery (HR 0.92, 95% CI 0.76–1.13, P = 0.4). Recovery was significantly more likely in patients with higher baseline eGFR, with no hypertension or peripheral vascular disease, and with certain causes of kidney failure (autoimmune renal disease, haemolytic uraemic syndrome, interstitial nephritis, obstructive uropathy, paraproteinaemia and renovascular nephrosclerosis). Recovery was less likely in Maori/Pacific Islanders and polycystic kidney disease. Among patients who recovered, 328 (78%) subsequently experienced renal death, mostly within the first year. The duration of renal recovery was not associated with initial dialysis modality (OR 0.82, 95% CI 0.50– 1.32).

Conclusions. Dialysis modality is not associated with the likelihood, timing or durability of spontaneous recovery of dialysis-independent renal function in patients thought to have ESRD.

Methods. The sample included 28 513 patients enrolled in DOPPS I and II. The classes of AHA studied were beta blocker (BB), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), peripheral blocker, central antagonist, vasodilator, long-acting dihydropyridine calcium channel blocker (CCB), short-acting dihydropyridine CCB and non-dihydropyridine CCB. To reduce bias due to unmeasured confounders, the associations with mortality were assessed by separate Cox models based on patient-level prescription and facility prescription practice.

Results. An increase in prescription of ARBs (9.5%) and BBs (9.1%) was observed from DOPPS I to II. Prescription of AHA classes varied significantly by country, ranging for BBs from 9.7% in Japan to 52.7% in Sweden and for ARBs from 5.5% in Italy to 21.3% in Japan in DOPPS II. Facilities that treated 10% more patients with ARBs had, on average, 7% lower all-cause mortality, independent of patient characteristics and the prescription patterns of other antihypertensive medications (P = 0.05). Significant and independent associations with reduction in cardiovascular mortality were observed for ARBs (RR = 0.79; P = 0.005) and BBs (RR = 0.87, P = 0.004) in analyses of patient-level prescriptions. These associations in the facility-level model followed the same direction.

Conclusions. DOPPS data show large variations across countries in AHA prescription for haemodialysis patients. The data suggest an association between ARB use and reduction in all-cause mortality, as well as with the use of BBs and reduction in cardiovascular mortality among haemodialysis patients.

Methods. The total body atherosclerosis score (AS) was determined by a magnetic resonance imaging-based angiography in 306 elderly men and women, representing a subsample of the community-based PIVUS cohort. Subjects were divided into three categories based on AS: AS = 0, low AS and high AS. Serum FGF23 was measured using a two-site monoclonal antibody ELISA.

Results. In continuous and multi-category regression models, higher FGF23 was associated with a significant increase in the odds of having a high AS (OR 1.43, CI 1.06–1.92 to OR 3.01, CI 1.52–5.99). This association was stronger in individuals with eGFR <60 mL/min/1.73 m² (n = 27), reaching a nearly 6-fold increase in the odds for a high AS in the upper FGF23 tertile (OR 5.64, CI 2.78–11.5). We found weaker support for a relationship between FGF23 and the presence of atherosclerosis as subjects in the highest FGF23 tertile had an increased risk for an AS > 0 in crude models (OR 1.93, CI 1.05–3.55), but this was not statistically significant in adjusted (OR 1.42, CI 0.74–1.72) models.

Conclusions. We provide novel evidence supporting an association between serum FGF23 and total body atherosclerosis in the community. Additional studies are warranted to determine the prospective relationship between FGF23 and atherosclerosis, and whether FGF23 is a modifiable cardiovascular risk factor.

Methods. Six weeks after the induction of AN, rats were treated with vehicle (n = 8), lisinopril (75 mg/L, n = 10), spironolactone (3.3 mg/day, n = 12) or the combination of lisinopril and spironolactone (n = 14) for 12 weeks. Age-matched healthy rats served as controls (n = 6). After 18 weeks, renal heparanase and heparan sulfate (HS) expression were examined by immunofluorescence staining. In addition, the effect of aldosterone, AngII and ROS on heparanase expression in cultured podocytes was determined.

Results. Treatment with lisinopril, spironolactone or their combination significantly blunted the increased glomerular heparanase expression and restored the decreased HS expression in the GBM. Addition of aldosterone to cultured podocytes resulted in a significantly increased heparanase mRNA and protein expression, which could be inhibited by spironolactone. Heparanase mRNA and protein expression in podocytes were also significantly increased after stimulation with AngII or ROS.

Conclusions. Our in vivo and in vitro results show that not only AngII and ROS, but also aldosterone is involved in the regulation of glomerular heparanase expression.

Methods. The Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgAN (PREDICT-IgAN) was a multicentre retrospective observational study to investigate associations between progression of IgAN (a 50% increase of serum creatinine level and slope of eGFR) and a hundred atherosclerotic disease-related gene polymorphisms, mainly single nucleotide polymorphisms (SNPs) in 320 IgAN patients who had more than a normal range of urinary protein (≥0.25 g/day) at diagnosis.

Results. During 8.3 ± 4.2 years of a follow-up period, 83 patients (25.9%) developed progression. In log-rank tests, glycoprotein Ia GPIa C807T and G873A and intercellular adhesion molecule-1 ICAM-1 A1548G (K469E) were found to be significantly associated with progression even after adjustment for multiple comparisons by the method of Bonferroni (adjusted P = 0.0174, 0.0176 and 0.0430, respectively). In a multivariate Cox proportional-hazards model, GPIa 807TT (873CC) [versus 807TT, adjusted hazard ratio 2.05 (95% confidence interval 1.13–3.71)] and ICAM-1 1548GG [versus 1548AA, 2.55 (1.40–4.65)] were identified as independent genetic predictors of progression, along with conventional clinical prognostic factors such as eGFR, urinary protein and use of antihypertensives at diagnosis.

Conclusions. PREDICT-IgAN distinguished GPIa C807T/ G873A and ICAM-1 A1548G from multiple athero- sclerotic disease-related gene polymorphisms by their predictive indicator for progression of IgAN.

Methods. In this study, we examined the effects of interleukin-1 beta (IL-1) on proximal tubular cell (PTC) response to TGF beta.

Results. IL-1 induced the rapid activation of NF-B in PTC. This was associated with inhibition of Smad2 and Smad3 signalling. NF-B activation by IL-1 was transient, with a change from p65/p50 heterodimer to p50/p50 homodimer formation by 24 h and a switch to enhanced Smad signalling response to TGF beta. This was associated with IL-6 generation and prevented by IL-6 receptor blockade.

Conclusion. In summary, IL-1 has a biphasic effect on PTC TGF beta signalling, with early NF-B-mediated inhibition and delayed sensitization via an autocrine IL-6 loop. These results provide mechanistic insight into how acute and chronic inflammation help define epithelial cell response to TGF beta, and hence how TGF beta can have apparently contradictory roles, being involved in controlled healing following acute injury on one hand, yet the principal promoter of scarring in chronic disease on the other.

Methods. Fifteen patients on RRT were submitted in random sequence to standard and reverse MD-HDF under similar operating conditions. Efficiency in solute removal was evaluated by measuring urea (U), phosphate (P) and beta2-microglobulin (β2-m), mean dialysate clearances (K_DQ) and eKt/V. Blood and dialysate compartment pressures were monitored on-line during the sessions, and instantaneous hydraulic and membrane permeability indexes were calculated.

Results. During standard MD-HDF sessions, unlike with reverse MD-HDF, excessive blood inlet and transmembrane pressure prevented the planned infusion from being maintained. Resistance index and membrane permeability to water and middle molecules substantially improved with reverse MD-HDF. This resulted in higher β2-m removal (221.3 ± 81.3 versus 185.1 ± 65.5 mg/session, P = 0.007). Phosphate removal was comparable, while U removal was greater with standard MD-HDF (K_DQ 272 ± 35 versus 252 ± 29 ml/min, P = 0.002; eKt/V 1.63 ± 0.23 versus 1.49 ± 0.17, P = 0.005).

Conclusions. This study demonstrated the ability of MD-HDF to remove significant amounts of medium-sized uraemic compounds and phosphate, but safe rheologic and hydraulic conditions were only maintained by carrying out treatments with the dialyser used in reverse configuration. For this purpose, the larger MD-220 dialyser ensured better tolerance together with higher middle molecules clearance, even though small molecule removal was slightly worsened. The results of this study may provide some insight into the complex interactions between pressures and flux within the original structure of MD-dialysers and help optimize the clinical application of the technique and reduce its risks.

Methods. Weekly eKt/V, equivalent renal clearance (EKR) and stdKt/V were compared retrospectively in 588 complete urea kinetic modelling sessions of 35 haemodialysis patients. Equivalent values of EKR and stdKt/V corresponding to the standard and high doses of the HEMO study were defined by computer simulation. The effect of frequency on the dose measures was demonstrated by simulating different schedules.

Results. EKR and stdKt/V take into consideration both frequency and RRF, but appreciate them differently. The values of EKRc (EKR in millilitres per minute, normalized to distribution volume 40 l), stdEKR (EKR in litres per week divided by urea distribution volume in litres) and stdKt/V corresponding to eKt/V 1.20—close to the standard dose in the HEMO study—were 13.2 ml/min/40 l, 3.34/wk and 2.23/wk, respectively. stdKt/V appreciates frequency more than EKR. A spreadsheet was created to compute the dialysis session time to achieve the EKR or stdKt/V target when the basic urea kinetic variables are known.

Conclusions. Haemodialysis efficiency can be increased by increasing frequency. EKR and stdKt/V are more appropriate than weekly eKt/V as measures of dialysis dose in different schedules. With increasing frequency, stdKt/V as the dosing target results in shorter treatment times and higher concentrations than EKR.

Methods. Kaplan–Meier and multivariate analyses were performed in a uniformly treated cohort of 145 patients with biopsy-proven AL who were monitored for at least 11 years. Outcome measurements were needed for renal replacement therapy and survival.

Results. Among patients presenting with renal AL, 42% ultimately received renal replacement therapy versus 5% of patients who did not have this presentation. Patients with renal amyloid who received dialysis support had significantly higher serum creatinine and 24-h urine protein levels at presentation. Patients with light chain amyloid were significantly more likely to have renal involvement and had significantly greater urinary protein loss than patients with light chain amyloid. Serum creatinine level was an independent predictor of overall survival when corrected for cardiac involvement. For 38 patients who received dialysis, median survival from Day 1 of dialysis was 10.4 months, and 26% of patients with AL ultimately received renal replacement therapy versus 42% of patients who presented with renal AL specifically.

Conclusions. Presenting 24-h urine protein loss and creatinine values predict which patients will require dialysis. Median survival for patients starting dialysis is <1 year. The presence of light chain amyloid predicts the increased likelihood of renal involvement.

Methods. Standard databases and reference lists of the pertinent literature were systematically searched. HAIDI was classified as ‘acute’ (<24 h after routine access construction), ‘subacute’ (within 1 month) or ‘chronic’ (>1 month). Location, type and follow-up of AVA were tabulated.

Results. Twenty-one studies reporting on surgically or percutaneously corrected HAIDI patients (n = 464) fulfilled the inclusion criteria. Acute HAIDI strongly (88%) correlated with non-autogenous AVA. In contrast, chronic HAIDI was predominantly (91%) observed following autogenous AVA based on the cubital segment of the brachial artery. A simple clinical classification for chronic HAIDI guiding treatment strategies is proposed.

Conclusions. Hand ischaemia occurring early after routine access surgery is usually related to grafts and not to autogenous access construction. If patients have several risk factors for acute hand ischaemia (diabetes), nephrologists and vascular surgeons may choose an autogenous AVA. A disadvantage of an autogenous access is its association with chronic hand ischaemia, particularly if constructed with a brachial artery.

Methods. RNA was extracted, labelled and hybridized to human specific genome wide DNA microarrays. Normalized data were subjected to gene-centric and pathway-centric statistical methods.

Results. Compared to the non-progressors, the 3-month biopsies of the progressor group showed overexpression of several genes that are important in the T- and B-cell activation and immune response. Genes involved in pro-fibrotic processes were identified in the biopsies of the progressors that preceded the observed IF/TA at 6 months. Furthermore, several genes with transporter and metabolic functions were underrepresented in the progressors in the 3-month biopsies.

Conclusion. Gene expression profiling of early protocol biopsies identified changes in the transcriptome of grafts, which may be important for the development of IF/TA. Such early detection of transcriptome changes can facilitate the identification of patients at risk shifting the intervention time point well before the histological diagnosis of irreversible IF/TA.

Methods. Rats were injected with a low (0.2 mg/kg) or high (4 mg/kg) dose of uranyl acetate (UA) to induce acute PT injury. Proliferating PT cells were labelled with bromodeoxyuridine (BrdU) before sacrifice. Renal tissues were examined by double labelling of BrdU and megalin, aquaporin 1 (AQP1), Na⁺–K⁺ATPase or vimentin, and by immunoelectron microscopy for BrdU+ cells.

Results. Under normal conditions, BrdU+ PT cells were positive for the PT phenotype (megalin-, AQP1- and Na⁺–K⁺ATPase positive and vimentine negative, a mesenchymal marker). Low-dose UA induced focal PT injury, and BrdU+ initially proliferating PT cells were found in the proximal three quarters of the S3 segment of nephron as early as 12 h, which maintained the PT phenotype and were vimentin negative. Proliferating PT cells showed low expression of the PT cell protein phenotype from Day 2 to Day 5 with vimentin expression from Day 2. High-dose UA induced severe PT injury in the proximal three quarters of the S3 segment by Day 5. BrdU+ initially proliferating PT cells, which were found in distal areas of the S3 segment as early as Day 2, showed low expression of the PT protein phenotype but were vimentin positive. Immunoelectron microscopy showed mature PT morphology for BrdU+ PT cells in control rats. BrdU+ initially proliferating PT cells showed a relatively mature phenotype after low-dose UA in- sult but an immature phenotype after high-dose UA insult.

Conclusions. PT cells can initiate cell division without de- differentiation after mild PT injury by low-dose UA insult.

Methods. A total of 845 ICU patients were analysed for cystatin C and classified according to the RIFLE criteria. Of these, 271 patients with either creatinine >150 µmol/l, urea >25 or anuria/oliguria entered the AKI cohort. The remaining 562 patients entered the non-AKI cohort. Both cohorts were divided into quartiles according to cystatin C at entry. In the non-AKI cohort, we split the highest cystatin C quartile into two. The relationship between the different cystatin C quartiles and mortality in patients with and without AKI was estimated by hazard ratios (HR) derived from the Cox proportional hazards regression model.

Results. A relationship between cystatin C and mortality was found in patients with and without AKI, being stronger in patients without AKI. In AKI patients, the HR comparing cystatin C above and below the median more than doubled from the second year on compared to the first year follow-up. After exclusion of patients in the non-AKI cohort with ‘potential AKI’ (creatinine >100 µmol/l or urea > 20 mmol/l), the correlation between cystatin C levels and risk of death was strengthened.

Conclusions. Cystatin C is correlated with mortality independently of renal function measured by creatinine in patients entering the general ICU.

Methods. We studied the outcome of borderline stenoses in accesses with PTFE grafts. Stenosis was considered significant if there was a combination of >50% lumen reduction and peak systolic ratio >2, together with at least one of the following additional criteria: (1) residual diameter <2.0 mm and (2) flow reduction of >25% or actual flow volume <600 ml/min. Stenosis was considered borderline in the absence of the additional criteria.

Results. Of the 102 borderline stenoses, after 11 ± 6 weeks, 55 remained non-progressive, in 38 the degree of the stenosis progressed, in 8 a percutaneous transluminal angioplasty (PTA) was performed due to clinical indication and only 1 thrombosed. A significant relative risk of developing significant stenosis was found in grafts with prior PTA [RR = 1.91 (95% CI: 1.27, 2.88), P = 0.002] and in female gender [RR = 2.29, (95% CI: 1.29, 4.06), P = 0.025].

Conclusions. Delaying PTA of borderline stenoses is safe using this watch-and-wait strategy and stenoses remain stable over at least short time, but with higher risk of progression especially after prior PTA. We believe that the definition of precise criteria of stenosis significance is necessary for the benefit of ultrasound surveillance.

Methods. In 182 living kidney donors, inulin clearance was measured under standardized conditions (protein, salt and water intake, overnight stay) before and after nephrectomy. Together with the serum creatinine level, and demographic and clinical data, 281 measurements of inulin clearance were used to compare the accuracy of different estimation equations. Using stepwise multiple regression, a new set of constants was defined for a CG-like equation in order to estimate GFR.

Results. The MDRD equation underestimated GFR by 9%, and the quadratic equation suggested by Rule overestimated GFR by 12.4%. The new CG-like equation, even when calculated with ‘mental arithmetic-friendly’ rounded parameters, showed significantly less bias (1.2%). The adapted equation is

Conclusions. We propose the CG-like equation called IB-eGFR (Inulinclearance Based eGFR) to estimate GFR more reliably than MDRD, Rule's equation or the original Cockcroft–Gault equation. As our data represent a Caucasian population, the adapted equation is still to be validated for patients of other ethnicity.

Methods. The authors examined this issue by analysing the clinical outcome of 281 RTRs. Hyperuricaemia (defined as UA > 7.0 mg/dl in men and >6.0 mg/dl in women for at least two consecutive tests, n = 121) was classified as early onset (within 1 year of transplant, n = 90) or late onset (n = 31). Graft function was estimated using the MDRD Study Equation 7 (eGFR_MDRD).

Results. As late-onset hyperuricaemia was found to be induced by a progressive decline in the graft function (P < 0.01), data from early-onset hyperuricaemic recipients were used. Early-onset moderate-to-severe hyperuricaemia (defined as UA ≥ 8.0 mg/dl) was found to be a significant risk factor for chronic allograft nephropathy (P = 0.035) and a poorer graft survival (P = 0.026) by multivariate analysis, whereas mild hyperuricaemia was not. The impact of moderate-to-severe hyperuricaemia on renal transplant survival was dependent on the duration of exposure. Likewise, the detrimental effect of early-onset hyperuricaemia on the graft function was dependent on UA levels and exposure time. After control of the baseline graft function by analysis of only recipients with a good graft function at 1 year post-transplantation (eGFR_MDRD > 60 ml/min), moderate-to-severe early-onset hyperuricaemia was also found to be a marker of long-term graft dysfunction and failure.

Conclusion. Moderate-to-severe early-onset hyperuri- caemia may be a prognostic marker of the long-term graft outcome in RTRs, which needs further investigation.

Methods. All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles.

Results. The study included 219 patients. Serum FGF-23 levels were high: 7060 ± 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3–5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality.

Conclusion. This study demonstrated a high level of circulating FGF-23 in LHD patients, despite infrequent hyperphosphataemia. However, phosphataemia is still the main factor correlating with serum FGF-23. The association of higher serum FGF-23 levels with mortality and VC, regardless of the serum phosphate levels, has thus been confirmed.

Objective. The aim was to describe the severity and outcomes of LN in a group of Thai children.

Methods. We retrospectively reviewed the patient files of children diagnosed with SLE aged ≤18 years in Songklanagarind Hospital, Southern Thailand, from 1985 to 2007.

Results. Of 216 SLE patients, 180 had renal biopsy results, and the others were excluded from analysis. There were 33 males and 147 females, average age 11.8 ± 2.6 years (range 3.6–18.0), with a median follow-up period of 3.9 years (range 9 days to 19.4 years). Using the WHO LN classification, there were 9, 55, 5, 94 and 14 patients of classes I–V, respectively, as well as 2 with end-stage renal disease and 1 with IgM nephropathy. The mortality rate was 23% (42/180). Patients with LN class II had a similar renal and patient survival compared to patients with LN class IV (P = 0.3 and 0.2, respectively). Cox proportional hazard regression analysis in 177 patients (3 patients who had a renal biopsy result outside the WHO classification were omitted) showed that gender was an independent risk factor for survival. Males had 2.6 times the hazard rate compared to females (95% CI 1.2–5.7, P = 0.03), but LN classification, age and timing of the renal biopsy were not significant.

Conclusion. Renal and patient survival in LN classes II and IV were similar. Gender was the only independent risk factor of mortality, with males at greater risk than females.

Methods. Using a provincial comprehensive set of administrative billing databases (outpatient visits, laboratory tests, pharmacy and hospital inpatient services), we itemized the prevalence of each and combination of conditions, resource utilization associated with each condition and combinations, using ICD 9-10 billing codes and standard definitions. Three consecutive years (2003–2005) were used to establish stability of findings.

Results. CKD, CVD and DM diagnoses are found in 422 124 persons within a province of 4.3 million individuals (10%); 1.7% had all three conditions. The median age of each cohort varied significantly between those with multiple conditions (67–79 years) versus those with single condition (56–72 years). The median number of physician visits was 26 per patient year. Duplicate testing accounted for expenditures of $3 million/annum; 7.55% of patients accounted for 34.4% of duplicate tests. Those with DM or CKD had similar use of medications, physician visits and hospital days. Those with all conditions (CVD–CKD–DM) had a median of 6 in-hospital days/year. A significant proportion were not on ACE/ARB or statin medications (30 and 45%, respectively).

Conclusion. Patients with chronic, complex conditions consume a large number of outpatient and inpatient resources. Documenting these allows identification of a set of metrics by which to design and measure health care system redesign initiatives. Potential targets to benchmark in designing more effective systems have been identified.

Methods. This study compares dialysis survival in two geographically similar areas, Scotland and British Columbia, Canada (BC). The effect of eGFR at dialysis start on survival was also measured. Incident adult dialysis populations of Scotland (n = 3372) and BC (n = 3927), 2000–05 were compared. Mortality Hazard ratios (HR) were calculated using a Cox proportional hazards model. Multivariate analysis included pre-dialysis eGFR, registry, age, sex, dialysis modality, year of start, pre-dialysis haemoglobin and primary renal diagnosis.

Results. Median survival times from start of dialysis were 38 (35–40) and 44 (42–47) months in Scotland and BC, respectively, giving an unadjusted mortality HR, Scotland versus BC, of 1.20 (95% C.I. 1.12–1.29). BC patients started dialysis at a higher eGFR (8.9 ml/min/1.73 m²) than Scotland (7.5 ml/min/1.73 m²), and prior to modelling higher starting eGFR was associated with higher mortality (1 ml/min/1.73 m² increase, HR = 1.028; 95% C.I. 1.021–1.035). BC patients were also older and had more diabetic renal disease. In multivariate analysis, lower starting eGFR was associated with better survival, and Scotland had greater mortality than BC. General population mortality and transplantation rate had only minor influence.

Conclusions. Concepts of ‘late’ versus ‘early’ start dialysis based on eGFR alone may need modification given the complexity and confounding reasons for dialysis initiation.

Methods. We used a 4-day CGMS to monitor glucose levels in 19 haemodialysed type 2 diabetic patients (HD T2) including 2 days with and 2 days without dialysis session, and 39 non-HD T2 in a double-centre study.

Results. The glucose concentration according to the glucose meter and CGMS were correlated in HD T2 patients (r = 0.90, P < 0.0001) and in non-HD T2 patients (r = 0.81, P < 0.0001). The relative absolute difference (RAD) between glucose determined by a glucose meter and glucose determined by the CGMS did not differ between HD T2 and non-HD T2 patients (9.2 ± 10.5 vs. 8.2 ± 7.6%; P = 0.165). Glycated haemoglobin (A1c) and mean glucose concentration were strongly correlated in non-HD T2 patients (r = 0.71; P < 0.0001) but weakly correlated in HD T2 patients (r = 0.47; P = 0.042). Fructosamine was correlated with the mean glucose concentration in non-HD T2 (r = 0.67; P < 0.0001) but not in HD T2 patients (r = 0.04; P = 0.88).

Conclusion. CGM is a validated marker of glycaemic control in HD diabetic patients. This tool showed that A1c and fructosamine, despite being good markers of glycaemic control in non-HD diabetic patients, are of poor value in HD diabetic patients.

Methods. A total of 74 haemodialysis (HD) patients and 35 control individuals (C) were studied. All subjects (mean age 62.9 years) provided fasted blood samples (HD patients after 66–69 h without dialysis). Circulating visfatin was measured by the ELISA. Body composition was evaluated using waist circumference, skinfold thickness and body impedance analysis. Results obtained by the ELISA were compared with EIA data.

Results. Active serum visfatin was increased in HD (5.58 ± 6.50 ng/ml) versus C [0.97 ± 1.79 ng/ml, mean ± SD; P < 0.0001 by multiple regression analysis (MRA)] independently of plasma glucose, serum insulin, diabetes, HDL cholesterol and body composition. Within the HD group, only plasma HDL cholesterol (4% lower per additional mg/dl HDL; P = 0.001) and insulin-treated diabetes mellitus [subgroup of n = 18; 119% higher compared with patients without diabetes (n = 40); P = 0.011] were independently (by MRA) associated with active serum visfatin. Visfatin measured by an EIA showed no correlation with ELISA data.

Conclusions. Our study provides reliable data on active visfatin in HD patients using a well-characterized ELISA. Loss of renal function is accompanied by increased circulating active visfatin concentrations in our patients. Furthermore, decreased HDL cholesterol may hint at an increased probability of cardiovascular events in HD patients with elevated serum visfatin.

Methods. Six HDP with near-normal [Hb] were tested for aerobic power ( ) and plasma [K⁺] during incremental exercise; quadriceps muscle strength (peak torque, PT) from 0 to 360° s^–1 and fatiguability (decline in strength during thirty contractions). Tests were conducted at baseline, after 6 weeks of normal activity (pre-train) and following 6 weeks cycle training (post-train). Six healthy untrained controls (CON) matched for age, sex, mass and height were tested at baseline.

Results. In HDP at baseline, and PT from 0 to 360° s^–1 were respectively reduced by 37% and 27–42%, compared to CON (P < 0.05). Plasma [K⁺], the rise in [K⁺] ([K⁺]) and the [K⁺] relative to total work done ([K⁺] work^–1 ratio) during incremental exercise were all higher in HDP at baseline compared to CON (P < 0.05). Exercise training increased time to fatigue by 12% (P < 0.05) but did not improve K⁺ regulation or . An inverse correlation was found between the [K⁺] work^–1 ratio and for pooled CON and HDP data.

Conclusions. In HDP treated with epoetin, poor exercise performance was related to impaired extrarenal K⁺ regulation, whilst training improved exercise performance but not K⁺ regulation. Thus, although impaired extrarenal K⁺ regulation may contribute to poor exercise performance in HDP, exercise performance can still improve with training despite unchanged K⁺ regulation.

Methods. Ischaemia was induced by unilateral renal artery clamping (40 min, I) followed or not by reperfusion (60 min, IR). NKA - and β-subunit abundance was analysed by western blot. We studied the NKA detergent sodium dodecyl sulphate (SDS) enzymatic activation in isolated membrane preparations from control and ischaemic kidneys.

Results. NKA activity was diminished in I cortical homogenates (C = 9.3 ± 1.1, I = 4.7 ± 1.1^* µmol Pi/h mg Prot, n = 4–6, ^*P < 0.05 versus C). This was rapidly recovered after reperfusion (IR = 9.9 ± 1.2 µmol Pi/h mg Prot). -subunit levels were increased, while β-subunit was unchanged. At SDS 0.9 mg/ml (maximal detergent activation), the activities were indistinguishable (C = 90.5 ± 2.2, I = 91.4 ± 15.1 µmol Pi/h mg Prot). The analysis of detergent activation of NKA activity is widely used to estimate membrane leakiness in plasma membrane preparations. Our results suggest a higher population of sealed impermeable vesicles in preparations from ischaemic renal tissue.

Conclusion. The well-known effect of ischaemia on renal cell cytoskeleton could explain the observed changes in the leakiness of membrane vesicles.

Methods. Four- and 24-h biofilms of Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans established in a microfermentor were exposed to ETOH and TSC for up to 24 h and the number of remaining viable microorganisms was determined.

Results. ETOH 60% was significantly more effective than 46.7% TSC in rapidly eradicating sessile cells from all microorganisms tested. A 20-min ETOH 60% treatment completely eradicated the Gram-negative bacilli and C. albicans biofilms, which initially contained up to 10⁸ and 10⁵ cells, respectively. Gram-positive cocci biofilms only showed a significant 2.6–4.3 log reduction in the initial viable counts after 20 min of ETOH 60% treatment, with eradication occurring after 30 min. Confocal laser scanning microscopy observation of ETOH-treated biofilm showed sparse cells with respiratory activity. TSC 46.7% eradicated none of the tested microorganisms. In contrast, ETOH 60% totally eradicated planktonic cells, whereas TSC had significant bactericidal activity against K. pneumoniae, P. aeruginosa and C. albicans after 20 min, 1 and 24 h, respectively, but none on the Staphylococcus species.

Conclusions. This in vitro study demonstrates the superior antimicrobial activity of ETOH 60% in contrast to TSC 46.7% in eradicating biofilm formed on a silicon catheter. Hence, ethanol-based solution shows promise as a catheter lock solution.

Methods. Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions.

Results. One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015).

Conclusions. If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients’ representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients’ personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Methods. Two groups of rats were treated with cisplatin, one of which being cotreated with -LA. The control group was treated with vehicle only. Four days later, the expression of aquaporins and sodium transporters was determined in the kidney by immunoblotting and immunohistochemistry. The arginine vasopressin-stimulated generation of cAMP was measured by radioimmunoassay. The expression of nitric oxide synthases (NOS) was determined by immunoblotting. The mRNA expression of endothelin-1 (ET-1) and tumour necrosis factor (TNF)- was measured by real-time PCR. Apoptosis was examined by TUNEL staining.

Results. Following the treatment with cisplatin, urinary volume and fractional excretion of sodium increased. Accordingly, the expression of aquaporins 1–3, Na,K-ATPase, NHE3 and NKCC2 was decreased. The expression of adenylyl cyclase VI and vasopressin-stimulated cAMP generation was decreased. The expression of inducible NOS was increased, while that of endothelial NOS decreased. The ET-1 expression was increased. TUNEL-positive cells were increased, in association with an increased expression of TNF-. -LA treatment prevented dysregulation of these parameters and resumed the renal function.

Conclusion. -LA may prevent the cisplatin-induced nephrotoxicity, possibly through preserving the activities of NO and ET systems and inhibiting the development of apoptosis.

Methods. Twenty-one patients with various GN were found to be serum HCV-antibody positive (seven serum HCV-RNA positive simultaneously), at the time of renal biopsy, from January 2005 to April 2008 in our hospital. A murine monoclonal antibody against the HCV-NS3 protein was employed to detect the HCV antigen using immunohistochemistry and immunogold labelling. Their clinical and pathological data were collected and further analysed.

Results. The HCV-NS3 antigen was detected in six (6/21, 28.6%) HCV-antibody-positive patients by immunohistochemistry and four out of the six were serum HCV-RNA positive (4/7 in HCV-RNA positive, 57.1%). The HCV antigen mainly displayed a linear or granular deposition along glomerular capillary walls and/or mesangial region. Immunoelectron microscopy showed that the labelling of HCV-NS3 was localized mainly in electronic dense deposits. In the HCV-NS3 detectable patients, three patients were with membranoproliferative glomerulonephritis (MPGN), one with membranous nephropathy, one with IgA nephropathy and one with amyloid nephropathy. The age and urinary protein were significantly greater in HCV-NS3-positive patients than those in HCV-NS3 negative, while serum C3 level was significantly lower in the former group. No significant difference was found in serum ALT, albumin and creatinine level between the two groups.

Conclusion. HCV-NS3 antigens could be detected in kidney tissue of HCV-infected patients with various GN, but mainly in those with MPGN and HCV-RNA positive. HCV itself might be involved directly in the pathogenesis of HCV-associated GN.

Methods. Discarded tissue segments were collected from the stenotic portions (usually near the graft-vein anastomosis or the AV anastomosis) of 23 dialysis grafts and 20 AV fistulae, and examined for expression of smooth muscle alpha actin, desmin, vimentin and a macrophage marker.

Results. The majority of cells within the venous neointima (both grafts and fistulae) were myofibroblasts, with a smaller number of desmin positive smooth muscle cells. The graft neointima had a similar cellular phenotype, albeit without any desmin positive contractile smooth muscle cells. The majority of cells within the PTFE graft material were macrophages. Analysis of sequential sections revealed the presence of fibroblasts within the venous neointima and intragraft region.

Conclusions. Our results demonstrate that contractile smooth muscle cells, myofibroblasts, fibroblasts and macrophages all play a role in the pathogenesis of dialysis access dysfunction (grafts and fistulae). Targeting these specific cell types might result in the development of novel therapeutic paradigms for haemodialysis vascular access dysfunction.

Methods. Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperaemia by PET. Peripheral artery endothelial function was examined by measuring flow-mediated dilatation (FMD) of the brachial artery at rest and during reactive hyperaemia. Twenty-two patients with moderate to severe kidney failure and 10 healthy controls were investigated. Diabetic patients were excluded. Baseline characteristics were similar between the groups with the exception of antihypertensive medication in all CKD patients.

Results. The basal myocardial perfusion was statistically significantly higher in CKD patients than observed values in similarly aged controls. There was a statistically significant negative correlation between the baseline myocardial perfusion and the estimated glomerular filtration rate. Coronary flow reserve was comparable to healthy controls in all patients. FMD was significantly reduced in all patients with CKD regardless of the stage of kidney failure.

Conclusions. Coronary flow reserve was normal although baseline myocardial blood flow was increased in all CKD patients as compared to healthy controls. Peripheral endothelial dysfunction was detected in all patients. Our findings suggest that coronary perfusion and peripheral vascular function are disturbed by different mechanisms in patients with CKD.

Methods. A total of 247 males and 258 females aged 40–62 years participated in this cross-sectional study. Renal function was assessed with estimated glomerular filtration rate (eGFR) and carotid atherosclerosis with ultrasonography as the mean IMT of the far carotid wall.

Results. The mean eGFR values were 90.2 (SD 16.8) ml/min/1.73 m² for men and 78.0 (SD 14.0) ml/min/1.73 m² for women, and the mean cIMT values were 0.92 (SD 0.21) mm for men and 0.82 (SD 0.12) mm for women. The mean cIMT was highest in the tertile with the lowest eGFR in both sexes (P = 0.013 for males and P = 0.031 for females). In males, the eGFR tertile was significantly associated with cIMT (P = 0.026) in a model adjusted for traditional risk factors. Renal function was also significantly associated with cIMT in a subset of 149 postmenopausal women (P = 0.008).

Conclusions. Even a minor deterioration in renal function was independently associated with increased cIMT in the middle-aged male population and in the postmenopausal women. This finding underlines the importance of early detection of subjects with mildly decreased kidney function and the aggressive management of atherosclerotic risk factors in this population.

Methods. We conducted a cohort study of 3358 vascular surgery patients between 1990 and 2006. CKD was defined according to the Modification of Diet in Renal Disease equation as an estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m². In addition, the patients were divided into three categories based on the baseline estimated GFR: ≥90 mL/min/1.73 m²; 60–89 mL/min/1.73 m² and <60 mL/min/1.73 m². Multivariable logistic regression analysis was used to evaluate the independent association between prevalent COPD and CKD.

Results. The prevalence of COPD was inversely related to kidney function. COPD was present in 47, 38 and 32% of patients with an estimated GFR <60, 60–89 and ≥90 mL/min/1.73 m², respectively. COPD was independently associated with CKD (OR 1.22; 95% CI 1.03–1.44; P = 0.03). This association was strongest in patients with moderate COPD (OR 1.33; 95% CI 1.07–1.65; P = 0.01). Both moderate and severe COPD were associated with increased long-term mortality in patients with CKD (HR 1.27; 95% CI 1.03–1.56; P = 0.03 and HR 1.61; 95% CI 1.10–2.35; P = 0.01, respectively), compared to patients without COPD.

Conclusions. Our findings indicate that COPD is moderately associated with CKD in a large cohort of vascular surgery patients. In addition, moderate and severe COPD are related to increased long-term mortality in patients with CKD.

Methods. For this observational, prospective multicentre cohort study, incident haemodialysis patients were recruited in 40 Italian centres and followed up for a mean period of 18 ± 6.7 months. Clinical characteristics and biochemistry were recorded at baseline. Comorbid conditions were scored by the Charlson comorbidity index (CCI).

Results. Data of 411 patients (mean age: 66.5 ± 14.8 years; 17.3% >80 years old) were recorded. The mean CCI was 4.17 ± 2.8. In patients with CCI >0, an inverse correlation was observed between CCI (excluding age) and iPTH (P = 0.00002). Independently of CCI, patients with iPTH <150 pg/ml had 76% as high as the risk of all-cause mortality. After multivariable adjustment, the combination of the first tertile of iPTH with second and third tertiles of CCI was significantly associated with all-cause mortality (RR = 3.83, P = 0.02; RR = 3.79, P = 0.01, respectively).

Conclusions. Incident haemodialysis patients suffer from a high rate of clinical complications. In these patients, low iPTH and high CCI are often associated and very likely responsible for an adverse outcome.

Methods. The donor graft, consisting of kidney, renal vein (RV), renal artery (RA) and a ureterocystic flap, was removed en bloc and perfused in situ. The donor RA was end-to-end anastomosed to the recipient left common carotid artery (CCA) using a sleeve anastomosis, and the donor RV was connected to the recipient right external jugular vein (EJV) using a cuff technique. During the vascular anastomosis, the kidney graft was placed in a lactated Ringer's solution ice-water preserving bag. The donor bladder patch was exteriorized to form cervical cutaneous stoma.

Results. A total of 104 heterotopic renal transplantations were performed, which included pre-experimental (62 operations) and experimental stages (42 operations). The success rates of the two stages were 80.6% and 95.2%, respectively. The time for surgery was 40 ± 6 min, the average time for donor surgery was 20 ± 5 min, the preparation time for the graft was 8 ± 2 min, the operative time for the recipient was 18 ± 3 min that included the time for the arterial anastomosis (5 ± 2 min) and venous anastomosis (2 ± 1 min), the cold ischaemic time of the graft was 15 ± 3 min and the warm ischaemic time of the graft was 2 ± 1 min.

Conclusion. We developed an easy and reliable model of cervical heterotopic kidney transplantation that may provide a useful tool for investigating kidney transplantation rejection and retransplantation pathology.

Methods. A total of 85 dialysis centres located in Portugal, France and Italy and belonging to the FME European dialysis chain were included. The current prospective analysis focuses on incident patients admitted to these centres between 1 January 2000 and 30 September 2005 with <1 month of previous follow-up on RRT. Data were gained from the FME EuCliD database. Patients were classified at baseline in four categories according to the BMI: underweight, normal range, overweight and obese. Also, the patient survival was analysed according to five quintiles of BW changes during the first year of HD treatment <–5.8%, –5.8 to –1.1%, –1.1 to 1.7% (reference category), +1.7 to +5.5% and >+5.5%. Survival analysis was adjusted for a set of demographic and comorbids using Kaplan–Meier curves and Cox model. Hazard ratios and their 95% confidence intervals were calculated with the use of the estimated regression coefficients and their standard errors.

Results. A total of 5592 patients were analysed (40.9% females), and the mean age at admission was 64.4 + 16.5 years. Of them, 27.7% were diabetic. The mean follow-up was 2.0 ± 1.6 years. Almost half of the patients (46.4%) were in the normal range of BMI (20–24.9 kg/m²). When analysed with the Cox model, the categories of baseline BMI (underweight, normal range, overweight and obese) significantly influenced the survival with the respective hazard ratio (HR) and confidence interval at 1.14 (0.96–1.35), 1, 0.74 (0.67–0.9) and 0.78 (0.56–0.87). The strength of the association as well as the shape of the curve remains unchanged after considering age, diabetes and comorbidities. Moreover, when compared to patients for whom BW remained stable during the first year of HD treatment, survival was significantly lower in patients presenting in the lower quintile of BW variation (<–5.8% in 1 year) with an HR of 1.6.

Conclusions. Despite increased comorbidities, overweight and obese patients on maintenance HD carry a significant lower mortality risk than patients in the normal and lower BMI ranges. This confirms the reverse epidemiology previously reported in US HD patients for these categories of BMI. Also BW variation during the first year of HD treatment is associated with patient survival, highlighting the importance of nutrition in this setting.

Methods. By means of high-throughput differential proteomic analyses and mass spectrometry techniques in CsA and vehicle-treated proximal tubule-derived cell lines of human and mouse origin, we determined proteins that change their expression in the presence of CsA.

Results. CsA-induced toxicity analyses revealed that 10 mM CsA for 24 h was the threshold condition to induce significant changes in cell viability and proteomic profile. We identified 38 differentially expressed proteins on CsA-treated mouse PCT3 and human HK-2 cells, related to protein metabolism, response to damage, cell organization and cytoskeleton, energy metabolism, cell cycle and nucleobase/nucleoside/nucleotidic metabolism. 1D and 2D western blot assays in crude extracts from CsA-treated cells or kidneys with impaired function upon CsA treatment revealed a correlation with proteomic changes or differential isoform expression, in randomly selected proteins.

Conclusions. Proteins identified in this work might be useful markers to eventually distinguish CsA toxicity from chronic allograft nephropathy in protocol biopsies of transplanted patients, facilitating the adjustment of CsA doses to non-toxic ranges, as well as to study the impact of potential therapeutic interventions in an animal model.

Methods. Adult patients with chronic kidney disease on dialysis who had initiated cinacalcet treatment were enrolled. Data were collected 6 months before initiating cinacalcet, at baseline (initiation of cinacalcet) and up to 12 months after cinacalcet initiation.

Results. A total of 1865 patients [mean (SD) age 58 (15) years] were enrolled from 187 sites in 12 countries. Most patients had a dialysis vintage of ≥1 year (1–5 years, n = 833; >5 years, n = 748 versus <1 year, n = 265). The patients generally had severely uncontrolled intact parathyroid hormone (iPTH) serum levels (median 721 pg/ml) and elevated phosphorus (median 5.9 mg/dl) and calcium (median 9.6 mg/dl) at baseline, despite being prescribed conventional therapies. The proportions of patients achieving the recommended [NKF-K/DOQI^TM (KDOQI^TM)] targets increased from baseline [4%, 39%, 40% and 46% for iPTH, phosphorus, calcium and calcium–phosphorus product (Ca x P), respectively] to Month 12 (28%, 48%, 51% and 68%, respectively). At Month 12, 18% of patients had achieved the combined target for iPTH + Ca x P compared with 2% at baseline. Most patients (65%) received <60 mg/day cinacalcet at Month 12. Vitamin D sterol use remained fairly stable throughout the study. There was a 13% decrease in prescribed sevelamer; use of calcium-based phosphate binders increased by 5.6%. There was no unexpected safety or tolerability concerns.

Conclusion. This analysis of current European clinical practice shows that—consistent with findings from randomized controlled trials and retrospective observational studies—cinacalcet improves attainment of KDOQI^TM bone metabolism targets in dialysis patients with various stages of SHPT.

Methods. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR.

Results. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 ± 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 ± 0.86 ng/ml) compared to healthy controls (1.17 ± 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN.

Conclusions. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative GN.

Methods and results. We report two patients presenting with dRTA, late sensorineural hearing loss and MSK, in whom molecular investigations demonstrated the presence of mutations of the H⁺ proton pump ATP6V1B1 and ATP6V0A4 genes.

Conclusions. These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.

Methods. From the UK Renal Registry (UKRR) database of patients receiving RRT between 1 January 1997 and 31 December 2004, we identified two cohorts: 2033 patients who had been on either haemodialysis (HD) or peritoneal dialysis (PD) for at least a year and who subsequently underwent transplantation and then survived at least a year (PD + HD to Tp); and 892 patients who had been on PD for at least a year who changed to HD and then survived at least a year (PD to HD). In both cohorts, the following variables were studied for the four quarters before and after the change of modality: blood haemoglobin and serum, ferritin, albumin, bicarbonate, cholesterol, calcium, phosphate and parathyroid hormone (PTH) concentrations. No information on drug treatment was available.

Results. In the PD + HD to Tp cohort, transplantation was associated with a rise in haemoglobin, albumin and bicarbonate, a fall in ferritin and phosphate, no change in calcium, a fall (but not to normal) in PTH and a transient rise in cholesterol concentrations. In the PD to HD group, the change in modality was associated with a significant temporary fall in haemoglobin, a progressive rise in ferritin, albumin, phosphate and PTH, no change in calcium and fall in bicarbonate and cholesterol concentrations.

Conclusion. The change from HD to PD is associated with a significant fall in the haemoglobin concentration; anticipation of this change might enable clinicians to ameliorate it. Persistent hyperparathyroidism is common after kidney transplantation.

Methods. We report on 11 large Cypriot pedigrees with three such mutations. A total of 236 at-risk family members were genetically studied, and 127 (53.8%) carried a heterozygous mutation. Clinico-pathological correlations were available in all of these patients. Renal biopsies in 21 of these patients all showed various stages of focal, segmental glomerulosclerosis (FSGS). Thirteen of these biopsies were also studied with EM and showed thinning of the glomerular basement membrane.

Results. Mutation G1334E (COL4A3) was found in six pedigrees, mutation G871C (COL4A3) in four and mutation 3854delG (COL4A4) in one pedigree. Clinical and laboratory correlations in all 127 mutation carriers (MC) showed that microscopic haematuria was the only urinary finding in patients under age 30. The prevalence of ‘haematuria alone’ fell to 66% between 31 and 50 years, to 30% between 51 and 70 and to 23% over age 71. Proteinuria with CRF developed on top of haematuria in 8% of all MC between 31 and 50 years, to 25% between 51 and 70 years and to 50% over 71 years. Altogether 18 of these 127 MC (14%) developed ESRD at a mean age of 60 years. Two members with different mutations married, and two of their children inherited both mutations and developed adolescent, autosomal recessive Alport syndrome (ATS), confirming that these mutations are pathogenic.

Conclusions. Our data confirm for the first time a definite association of heterozygous COL4A3/COL4A4 mutations with familial microscopic haematuria, thin basement membrane nephropathy and the late development of familial proteinuria, CRF, and ESRD, due to FSGS, indicating that the term ‘benign familial haematuria’ is a misnomer, at least in this cohort. A strong hypothesis for a causal relationship between these mutations and FSGS is also made. Benign familial haematuria may not be so benign as commonly thought.

Methods. We carried out a genetic analysis of endothelial nitric oxide synthase (eNOS) 894G>T, methionine synthase (MTR) 2756A>G and methylenetetrahydrofolate reductase (MTHFR) 677C>T/1298A>C in 268 renal allograft recipient/donor (D/R) matches, with respect to long-term graft survival.

Results. While MTHFR 677C>T/1298A>G and MTR 2756A>G polymorphism distribution in both recipients (R) and donors (D) showed no significant difference between matches with loss of graft function and those with long-term graft survival, the frequency of the eNOS 894TT genotype of donors was significantly increased (P = 0.040) in matches with better graft survival. The multivariate analysis identified the eNOS 894 genotype and clinically acute rejection episodes as independent risk factors for graft loss (P = 0.0406 and P = 0.0093, respectively).

Conclusions. The association between eNOS 894G>T polymorphism of donors and graft survival seems to suggest a role for this gene in chronic allograft injury; however, further studies are needed to confirm this hypothesis.

Methods. Data from the Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study, a prospective observational study from 54 ICUs in 23 countries of critically ill patients with severe AKI, were analysed. The RIFLE class was determined by using observed (o) pre-morbid and estimated (e) baseline SCr values. Agreement was evaluated by correlation coefficients and Bland–Altman plots. Sensitivity analysis by chronic kidney disease (CKD) status was performed.

Results. Seventy-six percent of patients (n = 1327) had a pre-morbid baseline SCr, and 1314 had complete data for evaluation. Forty-six percent had CKD. The median (IQR) values were 97 µmol/L (79–150) for oSCr and 88 µmol/L (71–97) for eSCr. The oSCr and eSCr determined at ICU admission and at study enrolment showed only a modest correlation (r = 0.49, r = 0.39). At ICU admission and study enrolment, eSCr misclassified 18.8% and 11.7% of patients as having AKI compared with oSCr. Exclusion of CKD patients improved the correlation between oSCr and eSCr at ICU admission and study enrolment (r = 0.90, r = 0.84) resulting in 6.6% and 4.0% being misclassified, respectively.

Conclusions. While limited, estimating baseline SCr by the MDRD equation when pre-morbid SCr is unavailable would appear to perform reasonably well for determining the RIFLE categories only if and when pre-morbid GFR was near normal. However, in patients with suspected CKD, the use of MDRD to estimate baseline SCr overestimates the incidence of AKI and should not likely be used. Improved methods to estimate baseline SCr are needed.

Methods. The small solute peritoneal membrane transport was evaluated in 34 patients before the start of PD. Twenty-two patients were treated with continuous ambulatory peritoneal dialysis (CAPD) and 12 with automated peritoneal dialysis (APD).

Results. Four months after the start of PD, the small solute peritoneal membrane transport increased only in CAPD patients (D/P_Creat, the ratio between dialysate solute concentration at the end of the PET and creatinine plasma concentration, changed from 0.66 ± 0.12 to 0.73 ± 0.07 in CAPD patients and from 0.64 ± 0.12 to 0.61 ± 0.07 in APD patients), and after about 16 months of PD, the peritoneal membrane transport was higher in CAPD patients (D/P_Creat = 0.74 ± 0.06) than in APD patients (D/P_Creat = 0.63 ± 0.10).

Conclusions. Performing the PET before and after the start of PD could provide relevant information about the characteristics of small solute peritoneal membrane transport and could be useful to evaluate the influence of PD modality on the changes in peritoneal membrane transport.

Methods. We studied n = 463 patients on chronic dialysis with angiographically confirmed (n = 218) or excluded (n = 245) CAD followed up for 65 months after initiation of dialysis. Monitored were arterial hypertension, diabetes mellitus, hyperlipidemia, smoking, CRP and fibrinogen. IL-6 gene G-174C polymorphism was determined by PCR amplification.

Results. The CC genotype was associated with an impaired patient survival (p < 0.05) remaining an independent risk factor for death in multivariate analysis (HR for CC genotype: 3.58, CI: 1.41-9.07, p < 0.01). CC genotype carrying CAD patients suffered significant frequently cardiovascular events (revascularization, myocardial infarction, death) compared to GG/GC genotype carriers (85.2% vs. 66.5, p < 0.05). However, the IL-6 gene G-174C polymorphism was not related to the onset and development of CAD itself (ns) and the inflammation parameters CRP and fibrinogen did not differ between the genotypes under investigation (ns).

Conclusions. Our results suggest that IL-6 gene G-174C polymorphism is associated with the incidence of cardiovascular events and mortality in chronic dialysis patients.

Methods. Eighty-two ESRD patients on HD were divided into low-flux HD (LF-HD), HF-HD and HDF groups. The melanin index (MI) and erythema index (EI) of the abdomen and the flexor side of the forearm (non-sun-exposed areas) and the forehead (sun-exposed area) were determined by using a narrow-band reflectance spectrophotometer at baseline and after 12 months.

Results. Even though absolute values of baseline and follow-up MI and EI of the three sites were comparable among the three groups, forehead MI and EI were significantly decreased after 12 months in the HDF group (P < 0.05). In addition, the change in forehead MI was significantly greater in the HDF than in the LF-HD group (–1.0 ± 2.4% versus 0.3 ± 1.6%, P < 0.05). Moreover, β₂-microglobulin reduction rates were negatively correlated with both changes in forehead MI (P < 0.01) and EI (P < 0.05).

Conclusions. Skin colour of sun-exposed areas was signi- ficantly decreased in ESRD patients receiving HDF therapy, suggesting that enhanced removal of MMW substances by convection may prevent or reduce hyperpigmentation in HD patients.

Methods. We have analysed retrospectively a cohort of 264 patients treated with PD in a single PD centre during 1994–2006. Patient characteristics, therapy measures and outcome of patients were compared between patients for whom PD was the initial method of renal replacement therapy (group 1, n = 197) and those transferred to PD from haemodialysis because of complications (group 2, n = 67). The Kaplan–Meier method and Cox proportional hazards multiple regression analysis were used to assess patient and technique survival.

Results. In patients transferred from HD, significantly less had diabetes (11.9% versus 38.1%, P < 0.0001) and there were also significantly more females (57% versus 42.2%, P < 0.05). Baseline Kt/V was significantly higher in the primary PD therapy group (2.46 ± 0.57 versus 2.11 ± 0.48, P < 0.001), due to lower residual renal function in patients transferred from HD. Group 2 had also significantly higher peritonitis rate (0.86 versus 0.62 episode/year, P < 0.05). During the time of observation, 71 patients have died, in 100 patients kidney transplantation was performed, 56 were transferred to HD, renal function recovered in 5 and 32 were still on PD at the end of the study. No significant differences were observed in unadjusted patient survival, but technique survival was significantly lower in group 2 (P < 0.05). In the Cox multiple regression model, diabetes status, age and albumin level significantly influenced survival. Relative risk of death was not increased significantly in patients transferred from HD.

Conclusions. Our data suggest that outcome of patients transferred from HD is similar to that achieved in patients in whom PD is the first choice therapy. Thus, this option should be strongly considered in patients experiencing complications on HD, mainly vascular access problems, heart failure or intradialytic hypotension.

Methods. Freshly isolated Mphi from Sprague–Dawley rats 2 weeks after 5/6-nephrectomy and from patients on intermittent haemodialysis (IHD) were stimulated by heat shock (HS) and compared to stimulated Mphi of control rats or healthy volunteers (CTR). Expression of HSP72 (inducible HSP70) was assessed by RT-PCR, and/or flow cytometry. Apoptosis of Mphi was detected by flow cytometry (CD14/annexin V-labelling).

Results. In rat Mphi, baseline HSP72 expression was similar in both groups, but its induction was significantly impaired in renal insufficiency (214 ± 68% less HSP70-mRNA versus CTR, n = 6). In patients, HSF-1-mRNA and HSP72-mRNA/protein response to HS was significantly lower, but not affected by dialysis session itself. In parallel, apoptosis of Mphi of patients was enhanced (+83 ± 29% constitutive apoptotic Mphi versus CTR, n = 8), and HS-dependent protection from apoptosis with and without serum depletion (48 h depletion: HS, +275 ± 37% apoptotic Mphi versus CTR, n = 6; full medium: +166 ± 62% versus CTR, n = 8, P < 0.05) was inferior.

Conclusions. Impaired HSP72 stress response of Mphi in patients on haemodialysis might contribute to the observed immune dysfunction and, therefore, to the increased susceptibility to infection and malignancy. Stress impairment is not restricted to uraemia but is already present in a rat model of chronic kidney disease.

Methods. We initially assessed these SNPs for association in UK type 1 diabetic patients with (cases; n = 597) and without (controls; n = 502) nephropathy using iPLEX^TM and TaqMan® assays. Replication studies were performed with DNA genotyped in a total of 2668 individuals from the British Isles.

Results. One SNP (rs4420638) on chromosome 19q13 was found to be significantly associated with diabetic nephropathy before (P = 0.0002) and after correction for multiple testing (P_corrected = 0.002). We replicated this finding in a phenotypically similar case–control collection comprising 709 individuals with type 1 diabetes (P = 0.002; combined P < 0.00001; OR = 1.54, 95% CI: 1.29–1.84).

Conclusions. Our case–control data suggest that rs4420638, or a functional SNP in linkage disequilibrium with this SNP, may be associated with diabetic nephropathy.

Methods. Forty-eight ADPKD patients (24.8 ± 0.8 years) with normal renal function (MDRD 108.1 ± 3.1 ml/min) and 21 age-matched controls were studied in a cross-sectional study. The urine albumin/creatinine ratio (UACR) above the upper range of controls (6.8 mg/g) was taken as the predictor of renal alterations and vascular remodelling. Urine MCP-1, MCP-1 fractional excretion (FE_MCP-1), endothelial-dependent vascular relaxation (EDVR), aortic pulse-wave velocity (Ao-PWV) and CIMT were chosen as biological markers.

Results. No differences between ADPKD with UACR ≤6.8 mg/g and controls were observed in urine MCP-1 (77.7 ± 13.9 versus 57.8 ± 6.3 ng/g), FE_MCP-1 (91 ± 19 versus 74 ± 8%) and CIMT (0.47 ± 0.06 versus 0.44 ± 0.07 mm), respectively. Conversely, ADPKD with UACR >6.8 mg/g showed values that were different from the two other groups. In addition, patients with UACR >6.8 and <20 mg/g showed greater values for urine MCP-1, FE_MCP-1 and CIMT (131.8 ± 21.7 ng/g, 159 ± 31% and 0.55 ± 0.05 mm, respectively), as compared with patients with UACR ≤6.8 mg/g. The same pattern was found in a subset of normotensive ADPKD patients. No differences were found in EDVR and Ao-PWV.

Conclusion. In young ADPKD patients, normal levels of UACR suggest that renal interstitium is comparable to that in healthy subjects and indicate an absence of subtle atherosclerotic changes in the carotid arteries. Likewise, early renal and vascular changes may be present at UACR below the levels defined as microalbuminuria.

Methods. In this study, we used a recently developed mucosal patch technique to evaluate the rectal mucosal inflammatory reaction to gluten in patients with IgAN (n = 27) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analysed for IgA and IgG antigliadin antibodies (AGA), IgA antibodies against tissue transglutaminase and IgA endomysium antibodies.

Results. Gluten reactivity, defined as increase in MPO and/or NO after gluten exposure, was observed in 8 of 27 IgAN patients. The prevalence of HLA-DQ2 and DQ8 was not increased among gluten-sensitive patients, and the total prevalence among IgAN patients was the same as for the normal population. An elevated serum IgA AGA response was seen in 9 of 27 IgAN patients. The increase in IgA AGA did not correlate with the gluten sensitivity as measured by NO and/or MPO. A specific serum IgG AGA response was seen in one patient only. Antibodies against tissue transglutaminase and endomysium were not observed.

Conclusion. It is concluded that approximately one-third of our IgAN patients have a rectal mucosal sensitivity to gluten, but without signs of coeliac disease, and we hypothesize that such sub-clinical inflammation to gluten might be involved in the pathogenesis of IgAN in a subgroup of patients.

Methods. Aortas of 31 patients with advanced CKD and of 31 age-and gender-matched controls were obtained at autopsy. Calcium and phosphorus content in the aorta was quantitated using x-ray analysis. The expression of calcification-promoting and calcification-inhibiting proteins was assessed using immunohistochemistry.

Results. The calcium and phosphorus content of the aorta was higher in CKD patients than in controls. Even in non-calcified aortic specimens of CKD, staining for Msx-2, BMP-2, bone sialo-protein, TNF- and nitrotyrosine was significantly more marked compared to controls. The same proteins were immunodetected in calcified aortic specimens of both CKD and controls. In contrast, staining for transglutaminase-2 and Fetuin A was significantly reduced in CKD. Higher expression of cbfa-1 and Pit-1 was observed in all calcified aortas with no difference between CKD and controls. The expression of TNF-, phospho-p38 and Msx-2 was correlated to the intensity of upregulation of BMP-2 and osteoblastic transdifferentiation by VSMC even in non-calcified areas of the aortas of CKD.

Conclusion. The expression of markers characteristic for calcification is not different in calcified aorta of CKD patients compared to controls, but in CKD patients, evidence of inflammation, transformation to an osteoblastic phenotype and reduced expression of transglutaminase are also found even in non-calcified aorta.

Methods. Using the provincial renal database in British Columbia (PROMIS), all patients receiving dialysis were tracked over the years preceding the implementation of a home haemodialysis programme and following its implementation. Rate of growth by specific dialysis modality (hospital haemodialysis, community haemodialysis, home haemodialysis, and peritoneal dialysis) were tracked.

Results. When comparing the provincial growth rates in the peritoneal dialysis programme, using the 4 years before and following the introduction of the home haemodialysis programme, they were unchanged both annually (7.84% versus 7.34%) and overall (25.27% versus 23.62%). The growth within the home haemodialysis programme appears to have come from the community haemodialysis programme (annual growth rate 12.28% versus 5.87%) and in-hospital haemodialysis (annual growth rate 4.61% versus 1.3%). Incident rates of dialysis were similar both prior to and following the introduction of the home haemodialysis programme. Finally, only 6.4% of the total patients entering the home haemodialysis programme had discontinued peritoneal dialysis within the 6 months preceding home haemodialysis training, indicating a low frequency of movement from peritoneal dialysis to home haemodialysis.

Conclusions. Successful implementation of a home haemodialysis programme can be done at a provincial level without having an adverse impact on the growth rate of existing peritoneal dialysis programmes.

Methods. Two clinical trials that enrolled patients with heart attack (N = 2481) or stroke (N = 3680) were combined to create our sample. The performance of the SCORED guideline was evaluated by standard diagnostic measures. Correlations among various risk scores and their predictive abilities for recurrent CVD were ascertained.

Results. For heart attack and stroke patients, respectively, the SCORED guideline yielded sensitivity of 94 and 97%, specificity of 27 and 11%, positive predictive value of 32 and 30%, negative predictive value of 93 and 89%, with AUC of 0.75 and 0.68. SCORED was strongly correlated with other risk scores and exhibited a similar performance in the prediction of recurrent CVD.

Conclusions. The higher risk of CKD in CVD patients with high SCORED values is demonstrated. This simple education and screening tool may help promote awareness of CKD in CVD patients, in addition to general populations, and assess the CKD risk and its relationship with recurrent CVD.

Methods. Male Han:SPRD rats with PKD (Cy/+) were treated with rapamycin (0.2 mg/kg/day IP) or vehicle from 1 to 12 months of age. Mean trough levels of rapamycin (ng/mL) were 6.6 ± 0.1 at 8 weeks of age. Twelve-month-old littermates (+/+) were used as normal controls.

Results. Twelve-month-old male Cy/+ rats treated with the vehicle had a more than doubling of kidney volume, severe chronic renal failure, severe hypertension and increased heart weight compared to normal littermate controls (+/+). After rapamycin treatment, 12-month-old Cy/+ rats had markedly improved kidney volume, renal function, blood pressure and heart weight not statistically different from controls. Rapamycin reduced the cyst volume density (CVD) by 72%. Mammalian target of rapamycin (mTOR) activation in the heart, as evidenced by a marked increase in the phospho-S6 protein that was inhibited by rapamycin, was demonstrated in 12-month-old Cy/+ rats.

Conclusion. In conclusion, long-term rapamycin treatment in Cy/+ rats results in a normalization of kidney volume, renal function, blood pressure and heart weight. The novel finding that rapamycin decreases hypertension, heart enlargement and mTOR signalling in the heart in PKD rats is reported. The only side effect of rapamycin treatment was an 11% decrease in body weight.

Methods. Chronic renal failure was induced in rats by 5/6 nephrectomy. Blood pressure, resting heart rate and plasma levels of creatinine, urea and asymmetric dimethylarginine (ADMA) were measured. To characterize the parasympathetic innervation of the heart, chronotropic responses to atropine, metipranolol and to vagal stimulation in the absence or presence of ADMA were investigated in vivo. In vitro, chronotropic and inotropic effects of carbachol and ADMA and mRNA expression of muscarinic M2 receptors, high affinity choline transporter (CHT1), vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) were assessed in the isolated cardiac tissues.

Results. In 5/6 nephrectomy rats, the resting heart rate was significantly higher and the parasympathetic tone, measured as the effect of atropine after administration of metipranolol was significantly lower than in control animals. Plasma ADMA levels were significantly elevated in the uraemic rats and significantly inversely correlated with the effect of atropine on the heart rate. No differences were revealed in the plasma norepinephrine concentrations, negative chronotropic responses to stimulation of the vagus nerves, chronotropic and inotropic responses to carbachol and the relative expression of M2 receptors, CHT1, VAChT and ChAT.

Conclusion. The data suggest that cardioacceleration in chronic renal failure is caused by a diminished cardiac parasympathetic tone in the presence of a functionally intact intrinsic cardiac cholinergic signalling system.

Genomic DNA was extracted from leukocytes, and all exons and exon–intron boundaries were analysed for NPHS1 using polymerase chain reaction and direct sequencing.

Results and Conclusions. Compound heterozygous mutations of NPHS1 were found in four patients and homozygous mutations in one patient. Interestingly, three patients out of five had the same mutation in NPHS1: nt2515(delC). Parents who had this mutation heterozygously were from neighbouring prefectures. Two among five patients in this research and one in the previous report (Kidney Int 2005; 67:1248–1255) had the same mutation: 736G > T in exon 7. All mutations including these two mutations except for one have never been reported outside of Japan yet.

Methods. A total of 120 male Sprague-Dawley rats were unilaterally nephrectomized or sham-operated and treated with AS101 or PBS. Kidney weight and protein/DNA ratio were assessed for each experimental animal. The expression of TGF-β, PCNA, CDK 2, pRb, ppRb, p21^Waf1, p27^kip1 and p57^kip2 proteins in renal tissues was determined by western blot analysis and immunohistochemistry, and the immunoprecipitation of cyclin E complexes was performed.

Results. Compensatory renal growth is initiated by proliferation of resident renal cells that precedes hypertrophy. Changes in TGF-β expression were positively correlated with the amounts of p57^kip2, but not with p21^Waf1 and p27^kip1 expression in the remaining kidneys. Moreover, there was a marked abundance of p57^kip2 but not p21^Waf1 and p27^kip1 binding to the cyclin E complex in PBS-treated unilaterally nephrectomized rats compared to sham-operated animals. Treatment of uninephrectomized rats with AS101 reduced kidney weight and protein/DNA ratio, inhibited TGF-β and p57^kip2 expression in the remaining kidneys, and decreased the level of p57^kip2 binding to cyclin E complexes.

Conclusion. These results demonstrate that TGF-β-induced compensatory tubular cell hypertrophy is regulated in vivo by p57^kip2 but not by the p21^Waf1 and p27^kip1 cyclin kinase inhibitor proteins.

Methods. We performed a 2-year follow-up study with an observational cohort of 311 CKD patients. The patients were examined by Doppler ultrasonography to calculate RI and AI to be calculated. Glomerular filtration rate (GFR) was estimated with the abbreviated MDRD study equation every 6 months.

Results. When we divided the patients into three groups by the RI value of 0.65 and 0.70, there were significant differences in the decrease in GFR among the three groups at 24 months. Kaplan–Meier analysis also showed a significant difference among the three groups in the survival rate of worsening renal function, which was defined as a decrease in GFR of at least 20 mL/min 1.73 m² or the need for long-term dialysis therapy until the end of the 2-year follow-up. Cox proportional-hazard analysis identified overt proteinuria (≥1.0 g/g creatinine), high RI (>0.70) and high systolic blood pressure (≥140 mmHg) as independent predictors of worsening renal function. In contrast, AI was of no significance in evaluating renal prognosis in CKD.

Conclusions. This study suggested that RI, and proteinuria and hypertension were independent risk factors for the progression of CKD.

Methods. A total of 6259 adults ≥25 years of age, without a history of alcohol dependence, participating in baseline (1999–2000) and follow-up (2004–2005) phases of an Australian population-representative study (AusDiab) were the subject of this analysis. Alcohol consumption status and volume/frequency were collected by standardized interviewer administered questionnaires and self-administered food frequency questionnaires. The outcomes were as follows: (i) 5-year decline in estimated glomerular filtration rate (eGFR) ≥10%, with baseline eGFR ≥ 60 and final eGFR <60 mL/min/1.73 m², and (ii) 5-year doubling of albumin to creatinine ratio (ACR) with final ACR ≥ 2.5 (males)/≥ 3.5 (females) mg/mmol, in the absence of albuminuria at baseline.

Results. Self-identification as a moderate or heavy, versus light, drinker was associated with elevated risk of albuminuria in males and females <65 years of age (OR, 95% CI: males 1.87, 0.99–3.52; females 2.38, 1.37–4.14). Odds of de novo eGFR <60 mL/min/1.73 m² were 0.34 (95% CI 0.22–0.59) and 0.68 (95% CI 0.36–1.27) in males and females, respectively, who were moderate–heavy drinkers. Alcohol intake of ≥30 g/day was associated with an increased risk of albuminuria after adjustment for age, sex and baseline kidney function (OR = 1.59, 95% CI 1.07–2.36), but a reduced risk of eGFR <60 mL/min/1.73 m² (OR = 0.59, 95% CI 0.37–0.95), compared with consumption of <10 g/day.

Conclusions. Moderate–heavy alcohol consumption may be an important modifiable risk factor for albuminuria in the general population. The natural history of alcohol-induced kidney damage and how this relates to markers of kidney function in the general population warrant further research.

Methods. Four hundred and sixty participants with MDRD GFR <60 ml/min/1.73 m² in the limited access Atherosclerosis Risk in Communities (ARIC) study database were divided into four resting heart rate groups: <60, 60–74, 75–89 and ≥90/min. The prevalence of metabolic syndrome at baseline across the groups was examined. Time to cardiovascular composite (myocardial infarction or fatal coronary artery disease event or stroke or coronary revascularization procedure) and time to all-cause death were examined in multivariate Cox models.

Results. The prevalence of metabolic syndrome in the <60, 60–74, 75–89 and ≥90/min groups were 41, 44, 69 and 82% (P < 0.001), respectively. In a multivariate Cox model adjusted for demographics, comorbidity, haemoglobin and physical activity, compared to the 60–74/min group, the hazard ratios of cardiovascular composite in <60, 75–89 and ≥90/min groups were 1.27 (95% CI 0.75–2.16), 1.79 (95% CI 1.07–2.99) and 1.37 (95% CI 0.54–3.44), respectively. In a similar model, the hazard ratios of death were 1.47 (95% CI 0.85–2.53), 3.11 (95% CI 1.93–5.02) and 3.97 (95% CI 1.99–7.94), respectively.

Conclusions. Resting heart rate is associated with metabolic syndrome in moderate CKD. Higher resting heart is associated with increased mortality and possibly cardiovascular events in this population. Interventional studies to examine whether a target resting heart rate of 60–74/min improves cardiovascular outcomes and survival in moderate CKD are warranted.

Methods. A group of 21 stable ESRD patients maintained on haemodialysis and a group of 21 age-matched normal control individuals were included in the study. Plasma apolipoprotein A-1, PLTP, CETP and LCAT levels were measured.

Results. Plasma triglyceride concentration was elevated and plasma HDL cholesterol, apolipoprotein A-1 and LCAT concentrations were significantly reduced, whereas plasma PLTP and CETP concentrations and activities were unchanged in the ESRD patients.

Conclusions. These findings point to acquired LCAT and Apo A-1 deficiencies and tend to exclude dysregulation of PLTP or CETP in the pathogenesis of HDL abnormalities in haemodialysis patients.

Methods. In this study, we examined whether administration of active vitamin D (calcitriol) or its analogue, 22-oxacalcitriol (maxacalcitol), is preventative in podocyte injury using the puromycin aminonucleoside nephrosis model with neither mesangial proliferation nor matrix accumulation.

Results. Before the onset of proteinuria, renal 1-hydroxylase and 24-hydroxylase were markedly down-regulated and up-regulated, respectively, leading to impaired vitamin D activation. Thereafter, serum 25-hydroxyvitamin D decreased along with the increased excretion of vitamin D-binding protein in urine. After confirming that podocytes express vitamin D receptor and all retinoid X receptors (RXRs) except RXR-, we found that daily administration of calcitriol or its analogue 22-oxacalcitriol ameliorated the nephrotic state by protecting podocytes, as shown by the reduced staining of desmin (podocyte injury marker) and the upregulation of nephrin and podocin. These data suggest that the impairment of the vitamin D system plays a role in increasing proteinuria in podocyte injury.

Conclusions. We demonstrated the breakdown of the vitamin D activation system in podocyte injury, and established a preventative role for vitamin D in podocyte injury.

Methods. Using unbiased stereological techniques, IV_glom was determined for 30 glomeruli in each of 24 adult male kidneys from Jackson, MS, USA (12 Caucasian and 12 African American). Half of each group had ‘high’ N_glom (>1.2 million nephrons per kidney) and the other half had ‘low’ N_glom (<600 000).

Results. Caucasians with high N_glom had a relatively homogeneous distribution of IV_glom as well as a relatively low mean value, while those with low N_glom had much greater heterogeneity of IV_glom, as well as a larger IV_glom (P < 0.0001) compared with those with high N_glom. This disparity was not apparent in African Americans, however, where subjects with both high and low N_glom showed substantial heterogeneity in IV_glom and larger mean values (P = 0.95).

Conclusions. High N_glom appeared to protect against glomerular enlargement and volume heterogeneity in Caucasians. However, substantial variation in IV_glom and net enlargement in glomerular size in African Americans with high nephron numbers suggest that additional forces, independent of low N_glom, are driving glomerular enlargement and heterogeneity.

Methods. We performed a community-based cross-sectional study with 923 individuals free from dementia and end-stage renal disease. Two groups were defined based on estimated glomerular filtration rate (eGFR): eGFR<60 mL/min/1.73 m² versus eGFR ≥ 60 mL/min/1.73 m². Outcome measures were scores from multiple clinical tests of specific cognitive abilities. The GFR classifications and serum creatinine levels were related to measures of cognitive performance using logistic and linear regression analyses with three sets of covariates: (1) basic (age, education, gender and race); (2) basic+risk factors for cardiovascular disease (CVD) and (3) basic+risk factors for CVD+stroke.

Results. An eGFR <60 mL/min/1.73 m² was present in 142 (15.4%) individuals; the mean (SD) eGFR in this subgroup was 49.7 (10.7). CKD was related to lower cognitive performance despite adjustment for CVD risk factors (CVD-RF). Adjusting for CVD-RF and stroke, odds ratios and 95% confidence intervals associated with performing in the lowest quartile of the distribution of the Global, Visual–Spatial Organization/Memory and Scanning and Tracking scores for the eGFR < 60 group were 1.97 (1.25, 3.10); 1.88 (1.21, 2.93) and 1.83 (1.56, 2.87), P < 0.01 with eGFR ≥ 60 group as the reference group.

Conclusions. Global performance and specific cognitive functions are negatively affected early in CKD. Targeted screening for cognitive deficits in kidney disease patients early in their disease course may be warranted.

Material and Methods. In 149 prevalent haemodialysis patients (82 men, mean age 53.9 ± 13.7 years), we evaluated the nutritional status by anthropometrics [post-dialysis height (H), body weight (BW), body mass index (BMI), mid-arm circumference (MAC), tricipital skin-fold thickness (TST), mid-arm muscle circumference (MAMC), corrected mid-arm muscle area (cMAMA) and three-category subjective global assessment score (SGA)], biochemical tests [protein equivalent of nitrogen appearance (nPNA), and pre-dialysis serum albumin, creatinine, total cholesterol, bicarbonate and haemoglobin (Hb) levels] and bioelectrical impedance analysis (BIA) to estimate body composition [percent body fat (%BF), fat-free mass (%FFM), body cell mass (%BCM), extracellular mass (%ECM) and the phase angle (PhA)].

Results. Age was found to be positively correlated with BMI (P = 0.001), and inversely correlated with %BCM (P = 0.013). Patients with A-category SGA were significantly younger (50.1 versus 63.7 years) than those with B-category SGA. Patients with diabetes had lower %BCM (32.9 versus 35.9%; P = 0.035) and PhA (5.5 versus 6.9°; P = 0.0007) than those without diabetes. The presence of heart failure was associated with significantly reduced nPNA (1.17 versus 1.34 g/kg day; P = 0.014), MAMC (22.0 versus 23.6 cm²; P = 0.041), %BCM (33.0 versus 36.1; P = 0.021), PhA (5.8 versus 7.0°; P = 0.031), serum albumin (39.7 versus 42.4 g/l; P = 0.013) and serum creatinine (8.1 versus 9.4 mg/dl; P = 0.010), and with a higher percent of B-category SGA (47.8% versus 22.6%; P = 0.019). Eleven deaths (7.4%) occurred during the follow-up period. Among general factors, age ≥ 55, the presence of diabetes, and dialysis vintage <2 years were associated with significantly reduced survival. Among nutritional factors, B-category SGA, nPNA <1.2 g/kg day, %BF <15% and PhA <6° significantly predicted mortality in both Kaplan–Meier and Cox analyses. The most important risk factor appeared to be nPNA; for every 0.1 g/kg day increase in nPNA, death risk decreased by 15%.

Conclusions. In our haemodialysis patients, advancing age, diabetes and heart failure were associated with worse nutritional status, as estimated by anthropometry, biochemical markers and BIA. Age ≥55 years, the presence of diabetes, nPNA <1.2 g/kg day, lower SGA score, %BF <15% and PhA <6° were associated with significantly increased death risk.

Methods. Male 2- to 3-month-old obese Zucker fa/fa (OZR) and ZDF fa/fa rats (ZDFR), and their control the lean Zucker rat (LZR), were used. Diabetic rats were given either a low dose (0.6 mg/kg/day) or a high dose (12 mg/ kg/day) of PGT in the chow for 2 or 4–5 months. Glycaemia, blood pressure, creatinine clearance and proteinuria were determined, and the underlying histopathology was defined with markers of fibrosis, glomerular damage, oxidative stress and inflammation by immunohistochemistry/ quantitative image analysis in tissue sections, and western blots and ad hoc assays in fresh tissue.

Results. PGT at low doses given for 4–5 months considerably reduced blood pressure, proteinuria and creatinine clearance. This was associated with amelioration of renal tissue damage and fibrosis, evidenced by the glomerulosclerosis, tubulointerstitial fibrosis, tubular atrophy and podocyte injury indexes, and of oxidative stress and inflammation, as shown by the decrease in the respective markers, although glycaemia remained high and obesity was not affected.

Conclusions. These results indicate that low doses of PGT ameliorate renal fibrosis and preserve renal function in this animal model of metabolic syndrome, independently of glycaemic control or effects on body weight.

Methods. DCS in 74 young CKD patients were evaluated: 25 pre-dialytic (PrD), 18 on dialysis (D) and 31 with transplants (T) compared to 32 healthy participants (C). Saliva and serum analysis included creatinine (Cr), urea (U), calcium (Ca), phosphorous (P), magnesium (Mg) as well as intraoral pH levels.

Results. All patient groups presented high DCS. DCS and pH levels were higher in the D group with a positive correlation between pH and lower incisor DCS (r = 0.56, P = 0.017). The highest salivary Ca was found in the PrD group. Salivary P in the PrD group was found to be higher than in the T and C groups. The lowest salivary Mg was found in the D group while the highest salivary Ca x P product was found in the PrD group. In all patient groups, salivary U was higher than in the C group with a 2.5-fold increase in the D group. Salivary Cr resembled the U salivary concentrations.

Conclusions. Alterations in salivary Ca, P, Mg, U, Cr and intraoral pH levels were observed in the patient groups. DCS correlated with renal disease severity and therefore may be a reflection of other tissue calcification pathologies found in these patients.

Methods and results. The 3-year cumulative incidence of death in a cohort of 476 patients on chronic haemodialysis treatment was 34.3% (SE 2.3). Sudden death had a 6.9% (SE 1.2) cumulative incidence, with 32 events representing 19.2% of all deaths, while cardiovascular not sudden death and noncardiovascular death accounted for a 3-year cumulative incidence of 7.3% (SE 1.2) and 20.1% (SE 1.9), respectively. According to Cox multivariate analysis, significant risk factors for sudden death were the presence of atrial fibrillation, diabetes mellitus, predialytic hyperkalaemia, haemodialysis mode and C-reactive protein level, which were associated with a 2.9 (CI_95% 1.3–6.4), 3.0 (CI_95% 1.3–7.2), 2.7 (CI_95% 1.3–5.8), 4.5 (CI_95% 1.3–15.5) and 3.3 (CI_95% 1.2–8.8)-fold increase in the risk of sudden death, respectively. Sudden death was significantly more frequent during the first 24 h of the first short interdialytic interval and during the last 24 h of the long interval, i.e. immediately before and immediately after the first weekly haemodialysis session (P = 0.02).

Conclusions. Our data show that the incidence of sudden death in haemodialysis patients is high and that atrial fibrillation, diabetes, hyperkalaemia, haemodialysis mode and C-reactive protein play an important role in developing fatal arrhythmia. Further studies will be necessary to define which interventions could be helpful in reducing this cause of mortality.

Methods.We identified 891 recipients with genealogy data in the UPDB with at least one year of follow-up, of which 145 (16.1%) had AR and 77 recipients had biopsy-proven rejection graded ≥1A. We compared the genealogical index of familiality (GIF) in cases and controls (i.e. recipients with random assignment of rejection status).

Results. We did not find evidence for familial clustering of AR in the entire patient population or in the subgroup with early rejection (n = 52). When the subgroup of recipients with rejection grade ≥1A (n = 77) was analysed separately, we observed increased familial clustering (GIF = 3.02) compared to controls (GIF = 1.96), although the p-value did not reach the level of statistical significance (p = 0.17). Furthermore, we observed an increase in familial clustering in recipients who had a rejection-free course (GIF = 2.45) as compared to controls (GIF = 2.08, p = 0.04). When all recipients were compared to non-transplant controls, they demonstrated a much greater degree of familiality (GIF = 2.03 versus GIF 0.63, p < 0.001).

Conclusions. There is a familial component to rejection-free transplant course and trend to familial aggregation in recipients with AR grade 1A or higher. If a genetic association study is performed, there are families in Utah identified in the current study that can be targeted to increase the power of the test.

Methods. Plasma malondialdehyde (MDA) levels, both total (tMDA) and free (fMDA), were measured as indexes of oxidative stress by gas chromatography-mass spectrometry. Bound MDA (bMDA) levels were calculated as the difference between tMDA and fMDA.

Results. Total and bMDA concentrations were significantly higher in patients than in controls (ESRD > HD > PD). In PD and HD patients, fMDA levels were similar and significantly higher than in ESRD. Multivariate analysis, with tMDA, fMDA and bMDA as dependent variables, showed similar and significant tMDA and bMDA relations with residual renal function (t = –2.160, P = 0.035) and albumin (t = –2.049, P = 0.045). Erythropoietin dose affected only fMDA values (t = –2.178, P = 0.034).

Conclusions. Free and bMDA concentrations identified different MDA patterns. Bound MDA, not excreted by kidneys, accounts alone for high tMDA concentrations in ESRD patients, while both fMDA and bMDA contribute to tMDA values in dialysis patients. These findings show that increased tMDA could be indicative not only of recent lipid peroxidation, and they also highlight the importance of evaluating free, bound and total MDA in patients with reduced renal function in order to assess their oxidative status.

Methods. Patients aged 16 years or older who underwent a renal biopsy at Severance Hospital in the Yonsei University Health System from 1987 to 2006 were enrolled. All medical records were reviewed retrospectively.

Results. In total, 1818 patients (M:F = 1.02:1) were reviewed. Glomerulonephritis (GN) comprised 85.9% of the total biopsied cases. The most common primary GN was IgA nephropathy (IgAN) (28.3%), which was followed by minimal change disease (MCD) (15.5%), membranous nephropathy (MN) (12.3%), focal segmental glomerulosclerosis (FSGS) (5.6%) and membranoproliferative GN (MPGN) (4.0%). The most common secondary GN was lupus nephritis (8.7%). The most common idiopathic nephrotic syndrome was MCD (38.5%), which was followed by MN and IgAN. Among 128 (7.4%) patients who were HBsAg-positive, MN (30.5%) and MPGN (21.1%) were the most common GN. When the incidence rates between 1987–91 and 2002–06 were compared, IgAN increased from 25.6 to 34.5%, while MCD (from 23.2 to 7.0%) and MPGN (from 6.7 to 1.7%) decreased significantly (P < 0.01).

Conclusions. IgAN was the most common primary GN, and MCD was the most common cause of nephrotic syndrome. In the 5-year quartile comparison, the relative frequency of IgAN increased, while the relative frequency of MCD and MPGN decreased significantly during the past 20 years.

Methods. We retrospectively reviewed the patients with occluded autogenous radial-cephalic fistulae receiving endovascular salvage via the radial artery approach in our institution. From January 2004 to July 2007, 48 patients fulfilling the above criteria were enrolled. Balloon maceration was used for patients with small clots. Mechanical thrombectomy with an Arrow-Trerotola percutaneous thrombolytic device or an AngioJet rheolytic catheter was used for patients with large clot burden. Outcome variables included anatomic and clinical success, complications and primary and secondary patency.

Results. All the transradial punctures were successful. Anatomic and clinical success was achieved in 96% of the cases. The post-interventional primary patency rates were 92%, 77%, 55% and 44% at 1, 3, 6 and 12 months, respectively. The post-interventional secondary patency rates were 96%, 93%, 89% and 89% at 1, 3, 6 and 12 months, respectively. The 12-month primary patency of the short-segment thrombus group was better than that of the long-segment thrombus group (57% versus 19%, P = 0.005). The complication rate was 4%. No puncture-site-related complications were noted, and all the radial arteries were palpable at follow-up.

Conclusions. An endovascular intervention through the radial artery approach is a safe and feasible strategy choice for restoring occluded autogenous radial-cephalic fistulae.

Methods. To assess the safety of low protein, we first conducted a nitrogen balance study in 34 incident PD patients randomized to receive in-centre diets containing 1.2, 0.9 or 0.6 g of protein/kg ideal body weight (IBW)/day for 10 days. Second, 60 stable PD patients [RRF 4.04 ± 2.30 ml/ min/1.73 m², urine output 1226 ± 449 ml/day, aged 53.6 ± 12.8 years, PD duration 8.8 (1.5–17.8) months] were randomized to receive either a low- (LP: 0.6–0.8 g/kg IBW/day), keto acid-supplemented low- (sLP: 0.6–0.8 g/kg IBW/day with 0.12 g/kg IBW/day of keto acids) or high-protein (HP: 1.0–1.2 g/kg IBW/day) diet. The groups were followed for 1 year and RRF as well as nutritional status was evaluated serially.

Results. A neutral or positive nitrogen balance was achieved in all three groups. RRF remained stable in group sLP (3.84 ± 2.17 to 3.39 ± 3.23 ml/min/1.73 m², P = ns) while it decreased in group LP (4.02 ± 2.49 to 2.29 ± 1.72 ml/min/1.73 m², P < 0.05) and HP (4.25 ± 2.34 to 2.55 ± 2.29 ml/min/1.73 m², P < 0.05). There was no change from baseline on nutritional status in any of the groups during follow-up.

Conclusions. A diet containing 0.6–0.8 g of protein/kg IBW/day is safe and, when combined with keto acids, is associated with an improved preservation of RRF in relatively new PD patients without significant malnutrition or inflammation.

Methods. Uric acid levels and microsatellite markers were assayed in the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort (1075 whites and 1333 blacks) and the Hypertension Genetic Epidemiology Network (HyperGEN) cohort (1542 whites and 1627 blacks). Genome-wide linkage analyses of uric acid and bivariate linkage analyses of uric acid with an additional surrogate of insulin resistance were completed. Pathway analysis explored gene sets enriched at loci influencing uric acid.

Results. In the GENOA white cohort, loci influencing uric acid were identified on chromosome 8 at 135 cM [multipoint logarithm of odds score (MLS) = 2.4], on chromosome 9 at 113 cM (MLS = 3.7) and on chromosome 16 at 93 cM (MLS = 2.3), but did not replicate in HyperGEN. At these loci, there was evidence of pleiotropy with other surrogates of insulin resistance and genes in the fructose and mannose metabolism pathway were enriched. In the HyperGEN-black cohort, there was some evidence of a locus for uric acid on chromosome 4 at 135 cM (MLS = 2.4) that had modest replication in GENOA (MLS = 1.2).

Conclusions. Several novel loci linked to uric acid were identified but none showed clear replication. Widespread diuretic use, a medication that raises uric acid levels, was an important study limitation. Bivariate linkage analyses and pathway analysis were consistent with genes regulating insulin resistance and fructose metabolism contributing to the heritability of uric acid.

Methods. We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden.

Results. Frequencies of four out of five selected SNPs (rs6957, rs2241715, rs1800471, rs1982073 and rs1800469) were found to significantly differ between male patients and male controls in a co-dominant model (corrected P ≤ 0.05) and of two SNPs (rs1982073 and rs1800469) in the allelic model (P ≤ 0.05 in 100 000 permutation test). Haplotype analysis for five selected SNPs revealed a significant association of TGGCG with protective effect (P = 0.0012, empirical P = 0.006, 100 000 permutations) and of CTGTA with susceptibility effect (P = 0.0018, empirical P = 0.008, 100 000 permutations). In our study, no association with TGFB1 variations was found when comparing female patients and female controls. No association was found for TGFB1 markers with disease progression for selected individuals from the patient's group. In addition, meta-analysis performed for SNP rs1982073 for combined patients and controls from our study together with published data from two independent studies showed a significant association.

Conclusions. Our experimental data together with the meta-analysis suggest TGFB1 as an important candidate gene for further biological studies of IgA nephropathy and as a possible target for therapy. Our data also indicate a possibility of a gender effect in the genetic background of IgA nephropathy.

Methods. We studied the effects of the calcimimetic R-568, R-568 with calcium (R-568 + Ca) or calcium (Ca) alone compared with control CKD rats on this triad in the Cy/+ male rat, a model of progressive CKD that spontaneously develops CKD-MBD on a normal phosphorus diet. Animals were treated for either 14 or 18 weeks beginning at 20 weeks of age (34-week and 38-week animals, respectively).

Results. The results demonstrated similar efficacy of R-568, R-568 + Ca and Ca in lowering PTH levels. R-568 alone lowered plasma calcium compared to control over time, but increased phosphorus compared to control early in the course of the disease, but not at 38 weeks. Animals treated with Ca alone or R-568 + Ca had lower phosphorus levels; the Ca alone group had elevated Ca levels. Bone volume improved in the calcium-treated groups. In contrast, arterial and cardiac calcification worsened by most assessments in the R-568 + Ca and Ca alone treated animals compared with R-568 alone whereas R-568 alone treatment showed beneficial effects on most sites of extraskeletal calcification.

Conclusion. Thus, R-568, with or without Ca, improved the biochemical abnormalities of hyperparathyroidism but with higher and lower calcium levels, respectively, compared with controls. However, R-568 + Ca had more dramatic improvement in bone volume, but more extraskeletal calcification than R-568 alone. This complexity demonstrates that treatment of one component of CKD-MBD may lead to undesirable effects on other components.

Methods. Ninety-one incident patients started CAPD for 12-month treatment with either LF (Balance®, Fresenius, n = 48) or CF (CAPD/DPCA®, Fresenius, n = 43). RRF, peritoneal solute transport rate and solute clearance were measured every 6 months.

Results. LF had a significant effect on the change of glomerular filtration rate (GFR) (P = 0.048 by the mixed model). In per-protocol analysis, GFR in the LF group did not decrease over a 12-month period, while GFR in the control group significantly decreased (0.13 ± 33.4 L/ week/1.73 m² for LF versus –13.6 ± 19.4 L/week/1.73 m² for CF, P = 0.049). Subgroup analysis for patients with initial GFR of 2 mL/min/1.73 m² or above showed a significantly higher GFR for the LF group over the 12-month period. At Month 13, serum total CO₂ levels were higher and serum albumin levels were lower in the LF group. No differences between the two groups were observed for the C-reactive protein. Over the 12-month period, effluent cancer antigen-125 levels significantly increased in the LF group, compared with those of the CF group, while effluent interleukin-6 levels were not different between the two groups.

Conclusion. Our study suggests that LF may better preserve RRF over the 12-month treatment period in incident CAPD patients.

Methods. To evaluate the independent relationships of estimated GFR and proteinuria with the mean level of and the circadian variation in blood pressure, we evaluated 336 patients, 184 (55%) patients with CKD (eGFR <60 or urine protein/creatinine >0.22) and 152 (45%) without CKD.

Results. The mean level of systolic and diastolic BP increased with increasing severity of proteinuria as well as with increasing impairment in GFR. When proteinuria and eGFR were considered together in the same regression model, proteinuria—not eGFR—was related to the severity of hypertension. Non-dipping was present in 52% of those with eGFR >60 and 55% in those with no proteinuria. Non-dipping was seen early in the course of impaired GFR or proteinuria. Adjusted for proteinuria, the odds ratio for non-dipping in those with CKD was 1.71 (95% CI 1.03–2.84, P = 0.036). The odds ratio for non-dipping in those with proteinuria was 1.75 (95% CI 1.00–3.08, P = 0.049) when adjusted for CKD. A cosinor model that evaluates the midline estimating statistic of rhythm (MESOR) and circadian variation revealed that proteinuria was a stronger determinant of MESOR compared to the CKD stage; the CKD stage in addition to proteinuria did not further add to the determination of MESOR. The amplitude of variation was markedly blunted in patients with the earliest stages of derangement in kidney function whether it was assessed by proteinuria or eGFR.

Conclusions. These results demonstrate a graded relationship of proteinuria and eGFR with the mean level of BP and a non-graded relationship with circadian variation. Consideration of these two simple tests of renal function may better assist in gauging the severity of hypertension in patients with CKD.

Methods. PRB of native kidneys was performed in 162 adult patients from February 2002 through February 2007 using real-time ultrasound and automated needle. Renal ultrasound (US) was performed at 1-h post-PRB to assess biopsy-related bleeding. Patients were observed for 24 h post-PRB to monitor clinically apparent biopsy-related complications. The value of the post-biopsy ultrasound in predicting complications was assessed.

Results. A clinically apparent complication was observed in 26 (16%) patients post-PRB (13 minor not requiring any intervention and 13 major requiring intervention). In patients with complicated courses, a haematoma at 1 h was seen in 77% (69% with minor and 87% with major complications). However, only 27 (20%) of 136 patients without complications (P < 0.0001) had a haematoma at 1 h. The presence of a haematoma 1-h post-PRB had a sensitivity of 77%, specificity of 80%, positive predictive value of 43% but a negative predictive value of 95% for predicting clinical complications.

Conclusions. We find that with the use of renal ultrasound 1-h post-PRB, the absence of perinephric bleeding is predictive of an uncomplicated course while the presence of a perinephric haematoma is not reliably predictive of a clinically significant complication post-renal biopsy.

Methods. We used the Vienna Health Screening Initiative, a longitudinal cohort study from 1990 to 2006, including 49 398 volunteers (49.9% women, age 20–89 years): n = 2487 showed mild CKD (proteinuria and GFR >60 ml/min/1.73 m²) and n = 392 showed moderate CKD (GFR = 30–59 ml/min/1.73 m²). The follow-up period was 5.5 ± 4.2 years; n = 148 cardiovascular deaths occurred. Exposure variables were BMI, glomerular filtration rate (GFR) and proteinuria. Cox regression models on cardiovascular mortality with adjustment for age, sex, log(cholesterol/HDL), uric acid, smoking, glucose, diabetes, mean blood pressure, hypertension and antihypertensive drug use were fitted.

Results. The risk factor paradox is shown in moderate CKD (GFR = 45 ml/min/1.73 m²): hazard ratios (HR) of BMI contrasts decreased consistantly from 1.28 (95% CI 0.33–5.82) at BMI 20 kg/m² versus 25 kg/m² to 0.76 (95% CI 0.38–1.50) at BMI 30 kg/m² versus 25 kg/m² and to 0.58 (95% CI 0.13–2.64) at BMI 35 kg/m² versus 25 kg/m², thus showing an inverse relationship compared to mild CKD/healthy participants. Examining proteinuria as an effect modifier in this context showed that in moderate CKD (contrast: proteinuria versus no proteinuria) HR decreased more profoundly from 9.43 (95% CI 2.66–27.40) at BMI 25 kg/m² to 3.74 (95% CI 0.93–15.70) at BMI 30 kg/m² and to 1.95 (95% CI 0.37–22.30) at BMI 35 kg/m², and conversely in non-proteinuric subjects, hazards for cardiovascular mortality increased in underweight as well as in overweight/obese subjects in a U-shaped manner.

Conclusions. Our results suggest that obese subjects with proteinuric CKD may not be counselled for weight reduction since a higher BMI was associated with a remarkably reduced risk of death.

Results. KRU declined during the first 5 years of HD from 3.1 ± 1.9 at 3 months to 0.9 ± 1.2 ml/min/1.73 m² at 5 years. The percentage of patients with KRU ≥ 1 ml/min at these time points was 85% and 31%, respectively. Patients with KRU ≥ 1 ml/min had a significantly lower mean creatinine (all time points), ultrafiltration requirement (all time points) and serum potassium (6, 12, 36 and 48 months). Nutritional parameters were also significantly better in respect to nPCR and serum albumin (6, 12, 24 and 36 months). Patients with KRU ≥ 1 ml/min had significantly lower erythropoietin requirements and erythropoietin resistance indices (12, 24, 36 and 48 months).

 Mortality was significantly lower in patients with a KRU ≥ 1 at 6, 12 and 24 months after HD initiation, this benefit being maintained after correcting for albumin, age, comorbidities, HDF use and renal diagnosis. Our unique finding was that these benefits occurred despite those with KRU ≥ 1 ml/min having a significantly lower dialysis Kt/V at all time points.

Conclusion. The associations demonstrated suggest that residual renal function contributes significantly to outcome in HD patients and that efforts to preserve it are warranted. Comparative outcome studies should be controlled for residual renal function.

Methods. This cross-sectional study included 37 dialysis patients (12 haemodialysis, 25 peritoneal dialysis), 33 pre-dialysis patients and 18 healthy controls. Both in vivo and in vitro (HUVECs) evaluations were used for the study. Circulating EMPs were measured by flow cytometry. The carotid artery intima–media thickness (cIMT) and pulse wave velocity (PWV) were measured by using high-resolution ultrasound. Study groups were compared for circulating EMP, cIMT and PWV. The relationship between EMPs and arterial stiffness and atherosclerosis was evaluated.

Results. The levels of PWV, cIMT, CD144 + EMP and CD146 + EMP in the dialysis group were significantly higher than those in the pre-dialysis and control groups (P < 0.05). Additionally, the levels of cIMT, CD144 + EMP and CD146 + EMP in the pre-dialysis group were significantly higher than those in the control group (P < 0.05). In all CKD patients, the CD144 + EMP was significantly positively associated with blood pressures, age, known duration of disease, CRP and PTH, and was significantly negatively associated with haemoglobin, GFR and albumin. The CD146 + EMP was significantly positively associated with blood pressures, age and CRP. In a multiple linear regression analysis, in the CKD group, cIMT was independently related to mean blood pressure and dialysis duration. PWV was independently related to the CD144 + EMP and mean blood pressure.

Conclusion. Our results suggest that endothelial damage starts in the early stage of CKD, that the endothelial dysfunction becomes overt with the increase of cardiovascular risk factors and that EMPs may be a reliable marker of the subclinical atherosclerosis and arterial stiffness.

Methods. We enrolled 270 patients with sufficient urine amount (daily urine volume >100 mL) from a medical centre in North Taiwan who began PD between January 1996 and December 2005 and followed them until December 2007. The study population was stratified by the decline rate of RRF into a fast, intermediate and slow decline group. The Kaplan–Meier survival analysis was used to determine patient survival and technique survival. The Cox regression model was used to identify factors associated with patient outcome. The proportional odds polychotomous logistic regression model was used to identify variables associated with rapid decline of RRF.

Results. During an average follow-up period of 45 months, 50 (18.5%) deaths, 67 (24.8%) death-censored technique failures (transfer to haemodialysis) and 43 (15.9%) renal transplantations occurred. The median rate of RRF decline was 0.885 mL/min/1.73 m² per year. Survival analysis showed that patients with fast RRF decline had worse survival and increased risk of technique failure. The multivariate Cox regression model confirmed that the rate of RRF decline was an independent factor associated with patient and technique survival and was a more powerful prognostic factor than basal RRF. Variables associated with a rapid decline of RRF were larger body mass index, presence of diabetes, prior history of congestive heart failure, use of diuretics, peritonitis episodes and hypotensive events.

Conclusions. Our data indicate that the rate of decline of RRF is a more powerful prognostic factor than baseline RRF associated with all-cause mortality and technique failure in patients on long-term PD. To prevent accelerated loss of RRF, it is imperative that every effort be made to avoid overdiuresis, peritonitis and hypotensive episodes, especially in those with diabetes, obesity and congestive heart failure.

Aims. We aimed to investigate renal water and sodium excretion and in parallel the segmental regulation of renal AQP2 and major sodium transporters in rats with acute LPS-induced endotoxaemia. Next, we aimed to examine the changes of iNOS expression and activated macrophage infiltration in the kidney and the effects of iNOS inhibition on AQP2 and NKCC2 expression in LPS rats.

Methods. Rats were treated with LPS (i.p.) or with LPS + iNOS inhibitor L-NIL, and 6 h later kidneys were subjected to semiquantitative immunoblotting and immunohistochemistry.

Results. Polyuria and increased natriuresis were seen 6 h after LPS injection alongside downregulation of both AQP2 and S256-phosphorylated AQP2 in CTX/OSOM and ISOM but not in inner medulla (IM). Thick ascending limb sodium transporters NHE3 and NKCC2 were downregulated in ISOM and NaPi2 was decreased in CTX/OSOM, whereas NCC and ENaC were not consistently downregulated. Immunolabelling intensity of iNOS was increased in vascular structures and transitional epithelium, and an infiltration of activated macrophages was seen in CTX and ISOM. L-NIL co-treatment prevented the downregulation of NKCC2 but not AQP2 in LPS rats.

Conclusions. Early downregulation of AQP2 and sodium transporters takes place segmentally in the kidney after LPS administration. In addition, an infiltration of activated macrophages and increased iNOS expression may play a role in the urinary concentrating defect in acute LPS-induced entotoxaemia.

Methods. Collagen deposition was evaluated in primary peritoneal fibroblasts following treatment with an A_2AR agonist and antagonist. In addition, peritoneal fibrosis was induced by i.p. injection of either chlorhexidine gluconate for 2 weeks or 4.25% glucose peritoneal dialysis fluid (PDF) for 1 month. The development of fibrosis was compared between wild-type (WT) and WT mice treated with caffeine (an A_2AR antagonist) in drinking water or between (A_2AR^+/+) mice and A_2AR-deficient mice (A_2AR^–/–).

Results. Adenosine or the A_2AR agonist CGS21680 stimulated collagen production by peritoneal fibroblasts in vitro and A_2AR antagonists (ZM241385 and caffeine) blocked this effect. Consistent with these results, caffeine-treated WT or A_2AR^–/– mice had reduced submesothelial thickness, collagen deposition and mRNA levels of fibroblast-specific protein (FSP-1) and connective tissue growth factor (CTGF). In addition, treatment with caffeine in vitro and in vivo diminished A_2AR and A_2BR mRNA levels induced by CG or PDF while it upregulated A₁R levels.

Conclusion. Our data suggest that adenosine through its A_2AR promotes peritoneal fibrosis and therefore should be considered as a target for pharmacological intervention.

Methods. Questionnaires were sent to 11 PD units in March 2007; cases were identified retrospectively. Outcome data on surviving patients were collected in March 2008.

Results. A total of 111 patients were identified; the mean time on PD was 82 months (range 8–247). Mortality increased with length of time on PD, being 42% at <3 years (n = 12), 32% at 3–4 years (n = 19), 61% at 5–6 years (n = 31), 54% at 7–8 years (n = 24), 75% at 9–10 years (n = 8) and 59% at >10 years (n = 17). Twelve patients had no previous peritonitis episodes, 28 had one previous episode, 30 had two previous episodes and 33 had three or more previous episodes. Of the patients with PD details available, 41/63 were high (>0.81) transporters and 44/71 had ultrafiltration <1 l/24 h, but 7/63 were low average transporters (0.5–<0.65) and 27/71 had ultrafiltration >1 l/24 h and a few had significant residual renal function. Sixty-five (59%) patients had their PD discontinued prior to diagnosis (51 HD; 14 transplanted). CT scans were performed on 91 patients and laparotomy on 47 patients. Drug treatment consisted of tamoxifen, immunosuppression or both. The median survival was 15 months in patients treated with tamoxifen (n = 17), 12 months in patients treated with immunosuppression (n = 24) and 21 months in patients who received both (n = 13), against 13 months (n = 46) in patients who received no specific treatment. Adhesionolysis was performed in 5 patients, and 39 patients were given parenteral nutrition. The overall mortality was 53% with a median survival of 14 months and a median time to death of 7 months.

Conclusion. This is one of the largest cohorts of patients with EPS in the literature. Long-term survival occurred in over 50%, regardless of the various treatments strategies undertaken by the centres.

Methods. We used conditional transgenic mice that express one of the HIV-1 accessory genes, vpr, selectively in podocytes using podocin promoter and the Tet-on system. These mice develop aggressive collapsing focal segmental glomerular sclerosis with massive proteinuria and deterioration of renal function within 4 weeks following heminephrectomy and doxycycline administration. Fluvastatin was administrated simultaneously with doxycycline, and the effect was compared with untreated controls after 4 weeks.

Results. Fluvastatin at 10 mg/kg/day significantly decreased urinary albumin excretion (87 versus 11 mg/day, P < 0.01) and glomerular sclerosis (2.4 versus 1.0, P < 0.01, assessed by semi-quantitative scoring: 0–4). Fluvastatin also decreased serum creatinine and total cholesterol, but these differences were not statistically significant (0.36 versus 0.32 mg/dl, P = 0.35; 492 versus 378 mg/dl, P = 0.11, respectively). Phenotypic changes in podocytes, as indicated by the downregulation of nephrin, Wilms’ tumour 1 and synaptopodin, along with upregulation of proliferating cell nuclear antigen, were attenuated by fluvastatin, suggesting its protective effects against podocyte injuries. In cultured podocytes, angiotensin II treatment decreased nephrin expression to 13% of basal levels, which was reversed to 58% by adding fluvastatin.

Conclusions. In conclusion, fluvastatin was effective in treating experimental HIVAN. The beneficial effect of this drug might be caused, in part, by preserving nephrin expression in podocytes against angiotensin II-mediated injury.

Methods. A retrospective cohort study of consecutive hospitalized HF patients was performed at a single centre from 1987 to 2002 with RRT data from the United States Renal Data System.

Results. Of 6276 HF patients without RRT on admission, 304 commenced chronic (≥3 months) RRT (280 dialysis only; 24 transplant) at a median of 475 days after dismissal. Overall incidence was 1.6% per year. Risk-adjusted incidence increased over time and was similar in those with preserved or reduced (<50%) ejection fraction. RRT patients were younger but had worse renal function and anaemia, and more diabetes, hypertension and coronary disease. Unadjusted survival was worse in the RRT group. However, risk-adjusted survival was similar in RRT and non-RRT groups (HR = 1.11, 95% CI 0.94–1.29, P > 0.05).

Conclusions. Our data show that although RRT is increasingly used in HF patients, the impact on risk-adjusted mortality remains to be established. Further studies should focus on defining the appropriate clinical settings in which RRT should be used in HF, the timing and type of RRT and whether RRT can improve specific outcomes.