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. Microarray analysis of isolated glomeruli was performed at Day 2, Day 10 and Day 15 in puromycin aminonucleoside nephropathy rats. Cytoskeletal genebank was established by sorting with the keyword ‘cytoskeleton’ from PUBMED genebank to identify the differential cytoskeleton genes. Microarray results were further confirmed by real-time PCR, western blot and double immunolabelling to validate their localizations.

Results. Nine different cytoskeletal genes were found to be involved in the dynamic changes of FPs in puromycin aminonucleoside nephropathy rats, including six up-regulated (Tagln, Actr2, Dnm3, Arc, Vcl and Birc5) and three down-regulated (Krt2–7, Nebl and Tnnc1). The differential expression of transgelin, survivin, arp2, cytokeratin7 and vinculin was verified by real-time PCR and western blot. Double immunolabelling revealed that five cytoskeletal proteins indeed colocalized with podocyte specific markers synaptopodin or -actinin-4. In addition, similar expression and distribution changes were detected in patients with proteinuric renal diseases and puromycin aminonucleoside-treated podocytes.

Conclusions. We identified five novel podocyte cytoskeletal proteins and found that they were associated with the dynamic changes of FPs in podocyte injury.

Methods. HUVEC were grown in the 3.5, 4.5 or 5.8 mg/dL concentration of extracellular Ca²⁺ for 2–3 weeks. Expression of adhesion molecules was analysed by flow cytometry. Endothelial nitric oxide synthase (eNOS), receptor of advanced glycation end-product (RAGE) and interleukin-6 (IL-6) mRNA expressions were determined by real-time PCR. eNOS, inhibitor kappa B (IB) and phosphorylated IB protein levels by Western blot, eNOS activity by conversion of [¹⁴C]-arginine to [¹⁴C]-citrulline, IL-6 and osteoprotegerin (OPG) secretion by ELISA and DNA-binding activity of nuclear factor kappa B (NFB)-p65 were assayed colorimetrically in nuclear extracts.

Results. In the presence of low Ca²⁺ (3.5 mg/dL), protein expressions and activity of eNOS were diminished, while the protein expressions of intercellular adhesion molecule-1 (ICAM-1), as well as the mRNA expressions of RAGE and IL-6, were elevated. The protein secretions of IL-6 and OPG were also stimulated in low Ca²⁺ concentration. At this concentration, the DNA-binding activity of NFB was enhanced, probably due to the decreased level of IB.

Conclusions. These results suggest that lower extracellular ionized Ca²⁺ may play a relevant role in modifying endothelial cells functions.

Methods. Cultured murine GEnC were stimulated with poly I:C RNA and phenotype changes were assessed. Specific antagonists or s.i.RNA were used to determine the mechanisms of RNA uptake and the functional role of putative RNA receptors.

Results. Poly I:C RNA activated GEnC to produce IL-6, CCL2, CCL5, CXCL10, IFN- and IFN-β. This was independent of endosomal acidification or MyD88 but required complex formation with cationic lipids to be taken up into GEnC via clathrin-dependent endocytosis. RIG-1- but not MDA5-specific s.i.RNA prevented GEnC activation. Type I interferon production did not activate GEnC in an autocrine–paracrine manner. Complexed RNA also activated GEnC to express ICAM-1 and increased the albumin permeability of GEnC monolayers.

Conclusions. Complexed dsRNA enters GEnC via clathrin endocytosis and activates GEnC via RIG-1 in the cytosol to produce inflammatory cytokines, chemokines and type I interferons. Furthermore, RNA induces ICAM-1 expression and increases GEnC permeability. All of these mechanisms may contribute to the onset or aggravation of glomerulonephritis associated with RNA virus infections.

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.

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. A retrospective cohort study of Cooperative Cardiovascular Project data for 87 693 Medicare beneficiaries ≥65 years old and ESRD free admitted to 4047 hospitals with acute myocardial infarction between February 1994 and June 1995 was conducted. Follow-up was collected through June 2004 for ESRD and mortality.

Results. Among 87 693 patients, 7.0% were African Americans and 50.1% females. African Americans had a higher prevalence of anaemia than whites (40.2% versus 26.7%, respectively; P < 0.001). Lower haematocrit was associated with higher ESRD rates after adjustment, and the association of haematocrit with ESRD did not vary according to race (P = 0.19). This association was strongest at the lowest baseline kidney function (GFR <15) with hazard ratios increasing 7-fold as haematocrit decreased from ≥ 42% to <28%.

Conclusions. In a nationally representative sample of patients with cardiovascular disease, anaemia was associated equally among African Americans and whites with an increased risk of ESRD.

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. 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. 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. 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 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. 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. 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. 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. 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. We measured leukocyte and monocyte subpopulations in 70 patients before and 10 min after haemodialysis initiation. Patients were stratified by their intra-dialytic CD14⁺⁺CD16⁺ monocyte drop (pre-defined major drop: decline of cell counts at 10 min to <50% of pre-dialytic values; pre-defined minor drop: decline to values >50% of pre-dialytic counts). Patients were followed up for 42 ± 2 months; endpoints were CV events and death.

Results. Patients with a minor CD14⁺⁺CD16⁺ monocyte drop had more CV events than patients with a major drop. In multivariate analysis, a minor CD14⁺⁺CD16⁺ monocyte drop was the strongest independent predictor of future CV events [hazard ratio 2.405 (95% CI 1.192–4.854)].

Conclusions. These data refute the assumption that a prominent intra-dialytic decrease of CD14⁺⁺CD16⁺ monocytes is detrimental. Instead, a minor cell drop could mirror CD14⁺⁺CD16⁺ monocyte dysfunction, with inadequate migratory reaction towards an immunologic stimulus posed by membrane and tubing contact.

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. 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. 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.

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. 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.

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.

Patients and methods. Biopsies for CMV examinations were obtained from 130 oesophagogastroduodenoscopies and 54 colonoscopies performed on 82 kidney transplant recipients, 49 dialysis patients with chronic end-stage kidney disease and 53 immunocompetent patients because of clinical indications. CMV was demonstrated by immunohistochemistry, both in frozen sections using a monoclonal antibody against CMV-specific antigens (pp65 matrix protein) and in paraffin sections by means of a monoclonal antibody against the delayed early protein (p52).

Results. CMV-positive cells were found in the gastroduodenal mucosa in 46 (68%) out of 82 kidney transplant recipients, in 9 (31%) of 49 dialysis patients and in 15 (45%) of 53 immunocompetent patients, in the colorectal mucosa in 7 (50%), in 6 (30%) and in 9 (45%) of the patient groups, respectively. In the transplant recipient group, 4 patients had severe and 10 patients moderate CMV infection in the gastroduodenal mucosa. CMV disease was diagnosed in two patients with severe infection and in one patient with moderate infection. All dialysis and immunocompetent patients had only moderate or mild CMV involvement.

Conclusion. It appears that CMV-positive cells were present in all groups studied, suggesting that CMV-infected cells alone are not sufficient to make the diagnosis of CMV disease in the transplanted host. Moreover, the clinical symptoms and the intensity of the histologic CMV findings did not correlate with the symptoms the patients were having. In kidney transplant recipients, it emerges that CMV is activated more easily in the upper rather than in the lower gastrointestinal tract.

We report a case of a 73-year-old male presenting with an enormous brachio-cephalic fistula aneurysm measuring 70–5.4 cm 20 years after successful renal transplantation. Despite attending regular renal outpatient clinic follow-up, this was only noticed as an incidental finding when the patient attended the emergency department after a fall that severely bruised his access. The patient subsequently underwent ligation with complete removal of the aneurismal fistula and discharged to a rehabilitation unit 3 days post-operatively.

Systematic closure of an arteriovenous fistula should be considered in all patients after successful renal transplantation to avoid potentially catastrophic complications of an arteriovenous fistula. In patients in whom the closure of vascular access is contraindicated, it is crucial to regularly assess the status of any arteriovenous fistula when following up patients after renal transplantation.