Methods. To this end, we have used immunofluorescence, immunohistochemistry and immunoelectron microscopy. We performed western blotting for the CRIM1 protein, using lysates from isolated glomerular podocytes and human renal tissue homogenate. By using quantitative PCR, we compared the CRIM1 mRNA levels in podocytes, human renal tissue homogenate, primary human renal proximal tubular epithelial cells and primary human pulmonary artery smooth muscle cells.

Results. The results show that in the human adult kidney, CRIM1 is mainly expressed in the glomerular podocytes and is associated with the insertional region of the filtration slit diaphragm (SD) of the podocyte pedicles.

Conclusions. CRIM1 is a protein that should be added to the list of proteins associated with the podocyte filtration SD and with the probable action of modulating BMP and VEGFA signalling.

Methods. Here we studied the nature of the glomerular filtration barrier to albumin in mice lacking the HS chains of perlecan either alone or in combination with podocyte-specific loss of agrin.

Results. The results show significant reductions in anionic sites within the GBM in perlecan-HS and in perlecan-HS/agrin double mutants. Podocyte and overall glomerular architecture were normal, and renal function was normal up to 15 months of age with no measurable proteinuria. Moreover, excretion of a negatively charged Ficoll tracer was unchanged as compared to control mice.

Conclusions. These findings cast further doubt upon a critical role for the GBM in charge selectivity.

Methods. In order to achieve these goals, HASMCs were incubated with IS. ROS were detected using probes with a fluorescence detector. The expression of alkaline phosphatase (ALP), osteopontin and organic anion transporters (OAT1, OAT3) was studied by western blotting. The expression of core binding factor 1 (Cbfa1), ALP, osteopontin and NADPH oxidases (Nox1, Nox2 and Nox4) was analysed by reverse transcription-polymerase chain reaction (RT-PCR). Knockdown of Nox4 was performed by RNA interference (RNAi).

Results. IS induced ROS generation and the expression of Nox4, Cbfa1, ALP and osteopontin in HASMCs. A NADPH oxidase inhibitor and antioxidants inhibited IS-induced ROS production and mRNA expression of Cbfa1 and ALP. Knockdown of Nox4 using small interfering RNA (siRNA) inhibited IS-induced ROS production and mRNA expression of Cbfa1, ALP and osteopontin. OAT3 was expressed in HASMCs.

Conclusions. IS induces ROS generation by upregulating Nox4, and the expression of osteoblast-specific proteins such as Cbfa1, ALP and osteopontin in HASMCs.

Methods. Wistar rats aged 8 weeks old were submitted to renal ablation of the right kidney—Unx rats (n = 10). 24 hours (n = 5) and 1 week (n = 5) after surgery, rats were anesthetized and the left kidney was removed. Urinary and plasmatic levels of catecholamines, sodium, urea and creatinine were measured. Gene expression of the amino acid and sodium transporters was determined by Real-time reverse transcription PCR. Protein expression was evaluated by Western blot using specific antibodies for the amino acid and sodium transporters.

Results. Uninephrectomized (Unx) rats for 24 h showed a lower urinary excretion of l-DOPA, dopamine and DOPAC than the corresponding Sham rats, accompanied by an increase in the expression of the Na⁺-K⁺-ATPase protein (64% increase). Unx rats for 1 week presented a hypertrophied remnant kidney, higher urine outflow and a ~2-fold increase in the fractional excretion of sodium. The NHE3 mRNA expression was significantly decreased in Unx rats throughout the study (~20% decrease). LAT1 transcript and protein were consistently overexpressed at both 24 h and 1 week after uninephrectomy. In contrast, 4F2hc and LAT2 transcript abundance was lower in 24-h Unx rats than in Sham rats (a 36% decrease in both cases).

Conclusions. These results provide evidence that the renal expression of the amino acid transporters LAT1, LAT2 and 4F2hc and the sodium transporters Na⁺-K⁺-ATPase and NHE3 is differently regulated following unilateral nephrectomy. In conclusion, this study allowed us to characterize the renal adaptations in the early stages after uninephrectomy, which showed a combined interaction of multiple mechanisms regulating sodium homeostasis including the renal dopaminergic system, and the abundance of amino acid transporters and sodium transporters.

Methods. Human proximal tubular epithelial cells (PTEC) were pre-treated with increasing concentration of a PPAR- agonist rosiglitazone or troglitazone (0–5 µM) followed by further incubation with the conditioned medium (IgA-HMC) collected from human mesangial cells (HMC) incubated with polymeric IgA isolated from IgAN patients. Gene expression of interleukin-6 (IL-6) and angiotensin II type 1 receptor (ATR1) was detected by reverse transcription–polymerase chain reaction (RT–PCR); protein expression of IL-6 and ATR1 was determined by ELISA and western blot, respectively. The mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2) activation was examined by western blot.

Results. An IgA-HMC conditioned medium prepared from IgAN patients increased gene expression and protein synthesis of IL-6 and ATR1 in PTEC when compared with a conditioned medium prepared from healthy controls. The upregulated gene expression and protein synthesis of IL-6 and ATR1 in PTEC induced by the IgA-HMC conditioned medium were readily attenuated following pre-treatment with a PPAR- agonist, thiazolidinedione (TZD). The ATR1-downregulating effect exerted by the PPAR- agonist occurred through the inhibition of ERK1/2 activation. The PPAR- antagonist, GW9662, significantly attenuated the inhibitory action of rosiglitazone on the increased synthesis of IL-6 and ATR1 protein.

Conclusion. Our current findings suggest that the PPAR- agonist attenuates excessive inflammatory response in activated PTEC in IgAN through suppressing ATR1 expression. This ATR1-downregulating effect is likely through the inhibition of ERK1/2 activation and is found to be PPAR- dependent. TZDs may possibly be new therapeutic additives to established treatment regime for renin–angiotensin system (RAS) blockade in IgAN.

Methods. In the prevention protocol, adult male Wistar rats received gentamicin (GM) [70 mg/kg, intraperitoneally (i.p), each 12 h for 7 days], NAC (20 mg/kg, sc, each 8 h for 7 days) and/or DFX (20 mg/kg, sc, at first, fourth and seventh days). In the treatment protocol animals received GM for 7 days. Additionally, animals received NAC and or DFX starting in the fourth day after GM administration. Parameters of renal function had been evaluated 24 h, 4 and 8 days after the beginning of GM administration in the prevention protocol and in Days 5 and 8 in the treatment protocol. At the end of experiment, lipid peroxidation (TBARS assay) and protein oxidation (protein carbonyls levels) formation were evaluated in kidney tissue as oxidative damage parameters.

Results. In the prevention protocol, GM-induced ARF was prevented by the NAC and DFX association. Lipid peroxidation was attenuated by both antioxidant treatments, but the effects of NAC plus DFX were of greater magnitude. In the treatment protocol, plasma markers of renal injury were improved only in the NAC group, despite the similar antioxidant effect of both NAC, DFX and NAC plus DFX.

Conclusion. Although the combination of NAC and DFX was more effective in the prevention protocol, the use of NAC alone seemed to be superior to NAC–DFX combination, in the treatment of GM-induced ARF in adult male Wistar rats.

Methods. HSC were isolated from mouse bone marrow and labelled with a cell tracker. Acceptor mice were subjected to unilateral ischemia and received HSC intravenously directly after reperfusion. In addition, in separate groups of acceptor mice, endogenous SDF-1 or HSC-associated CXCR4 was blocked or kidneys were injected with SDF-1.

Results. Exogenous HSC could be detected in the tubules and interstitium of the kidney 24 h after ischemic injury. Importantly, the amount of HSC in the ischemic kidney was markedly higher compared to the contralateral kidney. Neutralizing endogenous SDF-1 or HSC-associated CXCR4 did not prevent the migration of HSC. No increase in the number of labelled HSC could be observed after local administration of SDF-1, as was also determined in bilateral kidney ischemia.

Conclusion. In conclusion, systemically administered HSC preferentially migrate to the ischemic injured kidney. This migration could not be prevented by blocking the SDF-1/CXCR4-axis or increased after local administration of SDF-1.

Methods. Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed.

Results. At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 ± 0.28 mL/min versus 1.60 ± 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 ± 0.46 mL/min versus 0.75 ± 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores.

Conclusions. Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.

Methods. In a cross-sectional study among 842 outpatients with stable CVD, estimated glomerular filtration rate (eGFR), serum cystatin-C and urine albumin-to-creatinine ratio (ACR) were measured and serum ucMGP levels were determined by ELISA. Multivariate linear regression evaluated the association of each kidney function measure with serum ucMGP levels.

Results. The mean eGFR was 76 ± 23 mL/min/1.73 m², and 186 subjects (22%) had moderate CKD (eGFR <60 mL/min/1.73 m²). The mean ± SD ucMGP level was 3289 ± 1177 nM. In unadjusted analysis, each 10 mL/ min/1.73 m² lower eGFR was associated with 101 nM lower ucMGP level. This association was only minimally attenuated in final multivariate models wherein each 10 mL/ min/1.73 m² lower eGFR was associated with 79 nM lower ucMGP (95% confidence interval [CI]; 44 to 115; P < 0.001) after adjustment for age, sex, race, body mass index, blood pressure, smoking, hypertension, diabetes; and serum albumin, calcium, phosphorus, and fetuin-A levels. Similarly, in models adjusted for identical covariates, each 0.1 mg/L higher cystatin-C was associated with 39 nM lower ucMGP (95% CI 23 to 55; P < 0.001). In contrast, no significant association was observed between ACR and ucMGP in either unadjusted or adjusted analyses (adjusted P = 0.17). All associations were similar among subjects with or without diabetes (P-values for interaction > 0.50).

Conclusions. Among outpatients with stable CVD, a reduced glomerular filtration rate is associated with a decreased serum ucMGP level. In contrast, ACR is not associated with ucMGP levels. Whether ucMGP is a useful marker of vascular calcification and CVD event risk in persons with CKD deserves future study.

Methods. We conducted a retrospective chart review of 279 affected males and 168 females from 27 sites (USA, Canada, Europe). The pre-defined study endpoints included progression of renal, cardiac and cerebrovascular involvement and/or death before the initiation of enzyme replacement therapy.

Results. The mean rate of estimated glomerular filtration rate (eGFR) decline for patients was –2.93 for males, and –1.02 ml/min/1.73 m²/year for females. Prevalence and severity of proteinuria, baseline eGFR <60 ml/min/1.73 m² and hypertension were associated with more rapid loss of eGFR. Advanced Fabry nephropathy was more prevalent and occurred earlier among males than females. Cardiac events (mainly arrhythmias), strokes and transient ischaemic attacks occurred in 49, 11, 6% of males, and in 35, 8, 4% of females, respectively. The mean age at death for 20 male patients was 49.9 years.

Conclusions. Baseline proteinuria, reduced baseline eGFR, hypertension and male gender were associated with more rapid progression of Fabry nephropathy. The eGFR progression rate may increase with advancing nephropathy, and may differ between subgroups of patients with Fabry disease.

Methods. A total of 3143 subjects aged ≥40 years from 12 randomly selected communities in Karachi participated. MA was defined as the urine albumin to creatinine (ACR) ratio of < 300 mg/g creatinine and ≥17 mg/g in men and ≥25 mg/g in women from a single-spot morning urine sample. Major changes on ECG were coded in duplicate using Minnesota classification.

Results. The mean age of subjects was 51.5 (10.7) years. The median (25–75 percentile) ACR was 4.2 (2.9–7.9) mg/g in men and 6.0 (3.9–10.8) mg/g in women (P < 0.001). The overall prevalence (95% CI) of MA was 12.3% (11.1–13.5%), and 20.3% in those with major ECG changes. In a multivariable model, major ECG changes (OR, 95% CI) (1.50, 1.10–2.00), diabetes (3.57, 2.93–4.35), hypertension (2.30, 1.85–2.86), female sex (0.61, 0.53–0.69), age (1.09, 1.05–1.13, for each 5-year increase) and eGFR (0.80, 0.78–0.81, for each 10 mg/g increase) were independently associated with MA.

The presence of MA increased the prevalence of major ECG changes from 21 to 31% in those with hypertension (44.9%), 15 to 28% among those with diabetes (21.4%), 14 to 26% among those with overweight or obesity (68.4%) and 14 to 26% among current users of tobacco (38.7%) (P < 0.001) each.

Conclusions. The strong association between MA and major ECG changes underscores the importance of screening Indo-Asian subjects for MA for unmasking underlying CVD, especially those with hypertension, diabetes, obesity, and tobacco users.

Methods. A total of 2596 residents were randomly recruited from the community population in Shanghai, China. All were screened for albuminuria, haematuria, morning spot urine albumin-to-creatinine ratio and renal function. Serum creatinine, uric acid, cholesterol, triglyceride and haemoglobin were assessed. A simplified MDRD equation was used to estimate the glomerular filtration rate (eGFR). All studied subjects were screened by kidney ultrasound. Haematuria, if present in the morning spot urine dipstick test, was confirmed by microscopy. The associations among the demographic characteristics, health characteristics and indicators of kidney damage were examined.

Results. Two thousand five hundred and fifty-four residents (n = 2554), after giving informed consent and with complete data, were entered into this study. Albuminuria and haematuria were detected in 6.3% and 1.2% of all the studied subjects, respectively, whereas decreased kidney function was found in 5.8% of all studied subjects. Approximately 11.8% of subjects had at least one indicator of kidney damage. The rate of awareness of CKD was 8.2%. The logistic regression model showed that age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis each contributed to the development of CKD.

Conclusion. This is the first Shanghai community-based epidemiological study data on Chinese CKD patients. The prevalence of CKD in the community population in Shanghai is 11.8%, and the rate of awareness of CKD is 8.2%. All the factors including age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis are positively correlated with the development of CKD in our studied subjects.

Methods. Data were collected on age, sex, menstrual status, anthropometry, overnight urinary creatinine, dietary protein (overnight urinary urea), reported intake of milk/yogurt, serum creatinine, phosphate, calcium and total protein in 4034 adults (age 18–91 years) with GFR ≥60 mL/min x 1.73 m² as assessed by estimated GFR (eGFR, simplified MDRD equation) and creatinine clearance (overnight urinary creatinine/serum creatinine).

Results. The relationship of eGFR with serum phosphate was positive in men and null in women in univariate analyses (P = 0.001 and 0.148), negative in both sexes with age adjustment (P < 0.001). Age-adjusted results did not depend on colinearity between age and eGFR because the relationship was inverse also replacing eGFR with creatinine clearance (P < 0.001 in both sexes). In univariate regression analysis done separately by gender and six age-strata (18–24, 25–34, 35–44, 45–54, 55–64 and ≥65), the line of serum phosphate over eGFR was constantly inverse (range of P = 0.010/0.089) with the progressively lower y-axis intercept from young to older ages. The inverse relationship of eGFR or creatinine clearance with serum phosphate was significantly inverse also controlling for other variables (P < 0.01).

Conclusions. GFR differences in the range ≥60 mL/min x 1.73 m² are inversely and independently related to serum phosphate. The relationship is undetectable without age-controlled procedures because, for serum phosphate, the effect of GFR differences above ≥60 mL/min x 1.73 m² is much smaller than the effect of age.

Methods. LDL clearance was studied with a radiotracer method in 57 CKD patients and 10 healthy controls.

Results. In the CKD patients, the fractional catabolic rate of LDL apo B (LDL FCR), an indicator of LDL clearance from plasma, ranged from 0.13 to 0.56 pools/day with a mean value of 0.34 pools/day being comparable to that of the control subjects. In the renal patients, LDL FCR correlated significantly with estimated glomerular filtration rate (eGFR) (r = 0.340, P = 0.010) and this association remained significant after the adjustment with age, body mass index, gender, presence of diabetes and LDL cholesterol concentration (P = 0.004). In CKD patients with eGFR <15 mL/min/1.73 m² the mean LDL FCR was significantly reduced when compared to that of CKD patients with eGFR >30 mL/min/1.73 m² (P = 0.005). LDL apo B production rate was not associated with renal function or different between renal patients and control subjects.

Conclusions. The clearance of LDL seems to be related to the severity of renal impairment, but a remarkable reduction in LDL catabolism can be observed only in patients with advanced renal failure.

Methods. Questionnaires were posted electronically to all nephrologists who were in adult clinical practice in 2007 using the Australia–New Zealand Society of Nephrology register. The survey instrument assessed nephrologists’ reported practice towards colorectal, breast and cervical cancer screening across all stages of CKD (CKD 1–5, dialysis and transplantation).

Results. Of the 250 eligible members, 131 (52%) participated, with over 75% recommending breast cancer screening (usually 1–2 yearly using combined mammography and breast-self examination), 48% recommending colorectal cancer screening (1–2 yearly faecal occult blood test) and 86% recommending cervical cancer screening (1–2 yearly conventional cytology). Recommendations to screen did not vary appreciably with CKD status. Recommended screening strategies were more frequent, included more invasive tests, and were targeted at a broader age range than national cancer screening programmes in the general population. Increased cancer prevalence and cancer-specific mortality benefits for screening were the most commonly reported and influential criteria for making a positive recommendation.

Conclusions. Most nephrologists recommend breast and cervical, but not colorectal cancer screening in people with CKD. Despite the lack of trial-based evidence of benefits of screening in this setting, recommended screening practices by nephrologists are more intense than for the general population. Increased disease prevalence appears to be the most influential factor for making a positive recommendation to screen in the CKD population even though this is not an internationally accepted criterion for a screening programme, and is not relevant for breast cancer, which is not increased in the CKD population.

Methods. Patients with biopsy-proven MN, nephrotic-range proteinuria and clearance of creatinine 50 ml/min or more were included in the study. Exclusion criteria were treatment with steroids or cyclosporine during the previous 3 months, or cytotoxic agents within 6 months prior to entry. ET was administered subcutaneously, 25 mg twice per week for 3 months. Plasma levels of TNF-, interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), soluble intercellular adhesion molecule type 1 (sICAM-1), E-selectin, and the soluble form of tumour necrosis factor receptor-55 (sTNFR-55) were measured on entry and at Months 3, 6, and 9 after commencing therapy.

Results. Twelve patients were entered in the study (four females/eight males, mean time from diagnosis 8.3 months). The therapy was well tolerated; no infections or other adverse events were recorded by the end of follow-up. Two patients exhibited complete remission of proteinuria for at least 4 years. No significant change was found in the levels of TNF-, IL-1, IL-6, IL-8 and IL-10 during the study. Similarly the levels of E-selectin and sICAM-1 were not significantly altered by therapy. Although we found no change in sTNFR-55 at 3 and 6 months, the levels of sTNFR-55 were found significantly decreased 9 months after therapy (mean difference from baseline: 334 ± 527 pg/ml, P = 0.028).

Conclusion. Short-term use of ET in a small series of patients reduced sTNFR-55 levels but did not exhibit any significant clinical effect in the majority of patients.

Method. A total of 25 patients with biopsy-proven AAV and five healthy controls (HC) with normal renal histology were included. Renal biopsies were stained for mature (CD208), immature (CD209), plasmacytoid (CD303) and Langerhans (CD1a) DC subsets. Furthermore, T-cells were stained using a T-cell marker (CD3). The interstitial cellular infiltrate was graded semi-quantitatively from 0+ (= absence of cells) to 3+ (= numerous cells). Within the glomeruli, an absolute count was performed for positive cells.

Results. CD208+ and CD209+ cells were found within patients’ glomeruli but not in HC (1 ± 0.3 versus 0.08 ± 0.1 cells/glom; 2 ± 0.3 versus 0.1 ± 0.07 cells/glom). An average of 0.3 ± 0.1 cell/glom expressed CD3 in patients while few cells were found in HC (0.1 ± 0.7 cell/glom). Focal interstitial cellular infiltrates were observed in patients’ biopsies but not in HC. Interstitial infiltration with CD3+ and CD209+ cells was assessed at an average of 1+, but some glomeruli and tubuli were surrounded by CD3+ and CD209+ cells forming clusters. Serial sections revealed that CD209+ cells were present in CD3+ rich areas.

Conclusion. Both mature and immature glomerular DCs are found in renal biopsies of patients with AAV. Immature DCs cluster with T-cells in interstitial infiltrates in these biopsies. Since DCs form aggregates in T-cell areas, we hypothesize that these cells interact with each other and are involved in lymphoid neogenesis.

Methods. This prospective, observational study included 10 women with biopsy-proven relapse of proliferative lupus nephritis occurring during maintenance with mycophenolate mofetil (MMF) or azathioprine. The long-term outcome after a single course of the B-cell depleting anti-CD20 antibody rituximab (4 weekly infusions of 375 mg/m²), combined with daily MMF (2 g) and prednisolone (0.5 mg/ kg/day for 4 weeks, tapered thereafter) is presented.

Results. While renal function was not severely impaired at baseline, partial remission (>50% improvement in all abnormal renal parameters) was achieved in eight patients at a median of 3.5 months. In seven patients, with 24-h urinary protein of 2.5 ± 1.1 g (mean ± SD), complete remission, associated with increases in serum complement levels and decreases in anti-dsDNA titres, was subsequently established (normal serum creatinine/albumin levels, inactive urine sediment and 24-h urinary protein <0.5 g). Complete nephritis remission was sustained at the follow-up end (median of 38 months) in six patients. Combination treatment was well tolerated.

Conclusions. The efficacy of this low-toxicity combination was particularly evident in patients with subnephrotic proteinuria due to proliferative lupus nephritis relapse. Controlled trials to define the role of rituximab/MMF in this condition are warranted.

Methods. We established a urinary proteome pattern using capillary electrophoresis mass spectrometry (CE-MS) of 7 paediatric patients with cystinosis and 6 patients with ifosfamide-induced FS as the study group, and 54 healthy volunteers and 45 patients suffering from other renal diseases such as lupus nephritis (n = 8), focal segmental glomerulosclerosis (n = 27), minimal change disease (n = 7) and membranous glomerulonephritis (n = 3) as controls. Consequently, we conducted a blinded study consisting of 11 FS patients and 9 patients with renal disease other than FS. Additionally, we applied this pattern to 294 previously measured samples of patients with different renal diseases. Amino acid sequences of some marker proteins were obtained.

Results. Specificity for detecting FS was 89% and sensitivity was 82%. The marker peptides constituting the proteome pattern are fragments derived from osteopontin, uromodulin and collagen alpha-1.

Conclusions. CE-MS can be used to diagnose FS in paediatric patients and might be a future tool for the non-invasive diagnosis of FS. The reduced amount of the marker proteins osteopontin and uromodulin indicates loss of function of tubular excretion in all patients suffering from FS regardless of the underlying cause. In addition, the six different fragments of the collagen alpha-1 (I) chain were either elevated or reduced in the urine. This indicates a change of proteases in collagen degradation as observed in interstitial fibrosis. These changes were prominent irrespectively of the stages of FS. This indicates fibrosis as an early starting pathogenetic reason for the development of renal insufficiency in FS patients.

Methods. Consecutive abdominal tomographic scans performed during a 4-month period were evaluated and assessed for renal artery calcifications (RAC). Scans that showed calcifications were evaluated for renal artery narrowing and for various characteristics of the atherosclerotic plaque.

Results. Of 350 consecutive examinees, 43% were men, 40% had hypertension and 38% had hypercholesterolaemia. The age was 61 ± 13 years. Aortic calcifications were found in 54% and RAC in 102 (29%), of whom 53 had bilateral calcifications. Subjects with RAC were older, 72 ± 6 versus 55 ± 12 years. Adjusted odds ratios of RAC were 2.2 (95% CI 1.1–4.6) for male gender, 2.4 (1.2–4.8) for hypertension and 2.9 (1.4–5.8) for hypercholesterolaemia, whereas family history of hypertension was protective with 0.5 (0.3–0.9). All patients with calcified renal arteries had aortic calcifications, versus 35% of those without RAC. A significant correlation was found between the severity of calcifications and the degree of renal artery narrowing (r = 0.7), and also between the presence of bilateral calcifications and a high-grade narrowing.

Conclusions. RAC strongly relates to atherosclerosis. Calcifications and artery narrowing may have a role in the pathogenesis of hypertension. Bilateral calcifications suggest atherosclerotic renal artery stenosis.

Methods. We analysed retrospectively renal baseline characteristics and outcome in 58 patients including 2 patients on chronic haemodialysis undergoing TAVI at our institution. Acute kidney injury (AKI) was defined according to the RIFLE classification.

Results. Fifty-eight patients with severe symptomatic aortic stenosis not considered suitable for conventional surgical valve replacement with a mean age of 83 ± 5 years underwent TAVI. Two patients died during transfemoral valve implantation and two patients in the first month after TAVI resulting in a 30-day mortality of 6.9%. Vascular access was transfemoral in 46 patients and transapical in 12. Estimated glomerular filtration rate (eGFR) increased in 30 patients (56%). Fifteen patients (28%) developed AKI, of which four patients had to be dialyzed temporarily and one remained on chronic renal replacement therapy. Risk factors for AKI comprised, among others, transapical access, number of blood transfusions, postinterventional thrombocytopaenia and severe inflammatory response syndrome (SIRS).

Conclusions. TAVI is feasible in patients with a high burden of comorbidities and in patients with pre-existing end-stage renal disease who would be otherwise not considered as candidates for conventional aortic valve replacement. Although GFR improved in more than half of the patients, this benefit was associated with a risk of postinterventional AKI. Future investigations should define preventive measures of peri-procedural kidney injury.

Methods. A prospective randomized parallel group study was conducted in seven intensive care units of a tertiary university hospital. Pre-existing chronic kidney disease was an exclusion criterion. A total of 156 patients (570 screened) with AKI requiring renal replacement therapy were randomly assigned to receive standard dialysis [dosed to maintain plasma urea levels between 120 and 150 mg/dL (20–25 mmol/L)] or intensified dialysis [dosed to maintain plasma urea levels <90 mg/dL (<15 mmol/L)]. Outcome measures were survival at Day 14 (primary) and survival and renal recovery at Day 28 (secondary) after initiation of renal replacement therapy.

Results. Treatment intensity differed significantly (P < 0.01 for plasma urea and administered dose). No differences between intensified and standard treatment were seen for survival by Day 14 (70.4% versus 70.7%) or Day 28 (55.6% versus 61.3%), or for renal recovery amongst the survivors by Day 28 (60.0% versus 63.0%).

Conclusions. Although this study cannot deliver a definitive answer, it suggests that increasing the dose of extended dialysis above the currently recommended dose might neither reduce mortality nor improve renal recovery in critically ill patients, mainly septic patients, with AKI.

Methods. We investigated the 3-year survival and need for chronic dialysis in critically ill patients, who had survived an episode of AKI requiring continuous renal replacement therapy.

Results. A total of 206 ICU patients with AKI were randomized in a trial comparing haemofiltration versus haemodiafiltration. Of these, 95 (46%) survived at 90 days. Post-discharge information relating to 3-year survival and renal function was successfully obtained in 89 (94%) of the patients. Of the 89 patients studied, chronic kidney disease (CKD) was present in 32 subjects from the onset, and CKD developed de novo in 25 patients following AKI. End-stage renal disease (ESRD) developed in 9 patients (of whom 8 had pre-existing CKD) and 29 patients died. Three-year survival was 67% overall; the mortality at 3 years was 50% for those with pre-existing kidney disease, and 71 and 82% for those with de novo and without CKD, respectively.

Conclusion. After an episode of AKI necessitating a continuous renal replacement therapy, rapid progression to ESKD is commonly observed in patients with pre-existing chronic renal impairment. Medical care with an emphasis on nephroprotection is necessary in these patients.

Methods. In a retrospective design, 57 patients with brachiocephalic fistula access had radiology films of the cephalic arch reviewed for geometric analysis. Twelve patients were excluded from final analysis because of stent placement in the cephalic arch. Measurements made included diameter of the cephalic vein, minimum radius of curvature and angle of the arch. Demographics were statistically analysed to determine the association with the geometric measurements.

Results. Global and local measurements showed evidence of two arch types. Wider arch angles and larger R/d were associated with diabetes by univariate (P < 0.05) and multivariate analyses (P < 0.05). A wider arch angle was also associated with a history of right permcath access by multivariable analysis (P = 0.042).

Conclusions. Based on this study, it was found that there are two distinct types of cephalic arch geometries. Patients having diabetes mellitus show a significant probability of having a larger R/d ratio and wider arch angle. This study has given insight into structural alterations in geometry of the cephalic arch of diabetics with brachiocephalic fistula access.

Methods. We studied 2616 haemodialysis patients who had no or one vascular access change between January 2002 and June 2003. Two hundred and seventy-one patients switched from a catheter to an arteriovenous (AV) access (AV fistula or graft) and 69 patients from an AV access to a catheter. Accesses remained unchanged in 430 patients with catheters, and in 1846 patients with an AV access, who served as controls. Levels of serum albumin, white blood cell count (WBC), enPCR, eKdrt/V, blood haemoglobin and erythropoietin dosage were obtained monthly. Data were averaged over 6 months preceding (pre) and 6 months following the access change (post). Differences between post- and pre-access change were compared to changes in respective parameters between the last and first 6 months of the study period in controls.

Results. The change from a catheter to an AV access was associated with a rise of serum albumin (+0.12 g/dL; P < 0.001), enPCR (+0.05 g/kg body weight/day; P = 0.001) and haemoglobin (+0.41 g/dL; P < 0.001) and a decrease in WBC (–370/µL; P = 0.048). Conversely, switching from an AV access to a catheter was followed by a significant fall in albumin (–0.11 g/dL; P = 0.035), enPCR (–0.07 g/ kg body weight/day; P = 0.001) and eKdrt/V (–0.09; P < 0.001) and a rise in erythropoietin dosage (+89 IU/kg body weight/week; P = 0.002), as compared to controls.

Conclusion. Change from a catheter to an AV access seems to alleviate malnutrition, inflammation and anaemia. Efforts to replace catheters with fistulae or grafts should be intensified.

Methods. AVFs were created by a handsewn end-to-side anastomosis between the femoral vein and the femoral artery in 15 rats. A group of sham-operated animals (n = 3) served as controls. Time-related functional and morphological AVF characteristics were assessed up to 12 weeks using ultrasound (15-MHz transducer) and were correlated to histopathological changes.

Results. All rats survived surgery, and the patency rate was 93%. US showed a 2-fold increase in the fistula vein diameter and mean flow velocity as well as a 4-fold increase in the intima–media thickness without significant luminal loss. The afferent femoral artery exhibited no change in intima–media thickness and only minimal adaptive increases in diameter and flow velocity. Histological evaluation confirmed these observations.

Conclusions. Our AVF model in the rat demonstrates maturation effects in fistula veins similar to typical clinical findings in haemodialysis patients. Noninvasive ultrasound proved to be a valuable tool for longitudinal in vivo monitoring of the fistulas in this rodent model.

Methods. Ninety-nine HD patients, followed-up for 36 months, and 133 matched controls were genotyped for the two polymorphisms. HD patients’ characteristics were age 64 ± 13 years, males 64%, diabetic 24%, hypertensive 62%, smokers 38%, dyslipidaemic 28%, all undergoing standard HD thrice weekly.

Results. ESRD was strongly associated with the combination of 2G/2G and 6A/6A homozygosity: OR 2.57 (0.95–7.4), P = 0.037, but not with isolated 2G/2G and 6A/6A homozygosity (P = 0.09 and P = 0.11, respectively). Isolated 2G/2G was associated with all-cause mortality risk independently from age, gender, diabetes, hypertension, smoking, dyslipidaemia, C-reactive protein, albumin, dialysis vintage and history of cardio-vascular disease: HR 2.96 (1.29–6.80), P = 0.01. A trend for the association of mortality and isolated 6A/6A homozygosity was also observed: HR 3.01 (0.88–10.26), P = 0.078. Combination of 2G/2G and 6A/6A homozygosity significantly increased the mortality risk in the same Cox regression model: HR 4.69 (1.72–12.81), P = 0.003.

Conclusions. In this study, we demonstrated for the first time that MMP-1 and MMP-3 gene polymorphisms are negative prognostic risk factors for all-cause mortality in HD patients, independently from traditional risk factors. These data may have important implications for better understanding the pathogenesis of the increased mortality in HD patients.

Methods. Plasma retinol and malondialdehyde (MDA) levels were quantified by HPLC-UV/VIS; blood activities of catalase (CAT), superoxide dismutase (SOD) and -aminolevulinate dehydratase (ALA-D) were analysed by spectrophotometric methods, in HD patients (n = 29) and healthy subjects (n = 20).

Results. The MDA and retinol levels, SOD and CAT activities were significantly increased in HD patients. ALA-D activity was significantly decreased. Retinol levels were correlated with MDA levels (r = 0.68), CAT (r = 0.39), SOD (r = 0.40) and ALA-D (r = –0.55). A partial correlation between retinol levels with ALA-D (r = 0.43), SOD (r = 0.30) and CAT (r = 0.36) activity was found, utilizing MDA levels as co-variable.

Conclusion. Higher retinol levels may be associated with the increase of SOD and CAT activities, but this increase was not sufficient to prevent the lipid peroxidation and ALA-D thiolic group oxidation. In this manner, our results could suggest that high retinol levels contribute as an additional factor to the oxidative tissue damage.

Methods. Transport between intra- and extracellular spaces was modelled by diffusion using a specific rate constant k_s for creatinine equilibration in whole blood (0.022 min^–1) determined in a separate study. This k_s was applied to all body spaces and to creatinine removal from blood coursing through the dialyzer. Erythrocyte and plasma creatinine and urea concentrations during haemodialysis measured and reported by others were used to test the model.

Results. The model accurately predicted the reported time course of creatinine in plasma and erythrocytes as well as the time course of urea in plasma when using the much higher k_s for urea (158 min^–1). However, it did not explain an increased erythrocyte to plasma urea gradient found at the end of haemodialysis.

Conclusion. The results suggest that a diffusion-adjusted regional blood flow (DA-RBF) model can be used to explain compartmentalization of creatinine or urea throughout the body during haemodialysis, although possible additional compartmentalization of urea in erythrocytes, and perhaps in the tissues, still needs to be accounted for. This new model should be applicable to modelling of other non-protein-bound candidate uraemic toxins, also.

Methods. This study was based on two-compartmental kinetic data obtained in stable haemodialysis patients (n = 7) for urea, creatinine (CREA), guanidinosuccinic acid (GSA) and methylguanidine (MG). For each individual patient, mathematical simulations were performed for different dialysis schedules, varying in frequency, duration and intensity. For each dialysis schedule, plasmatic and extraplasmatic weekly time-averaged concentrations (TAC) were calculated, as well as their %difference to weekly TAC of the reference dialysis schedule (three times weekly 4 h).

Results. Increasing dialysis duration was most beneficial for CREA and MG, which are distributed in a larger volume (54.0 ± 5.9 L and 102.6 ± 33.9 L) than urea (42.7 ± 6.0 L) [plasmatic weekly TAC decrease of 31.5 ± 3.2% and 31.8 ± 3.8% for CREA and MG with Q_B of 200 mL/min, compared to 25.7 ± 3.2% for urea (P = 0.001 and P < 0.001)]. Increasing dialysis frequency resulted only in a limited increase in efficiency, most pronounced for solutes distributed in a small volume like GSA (30.6 ± 4.2 L). Increasing both duration and frequency results in weekly TAC decreases of >65% for all solutes. Comparable results were found in the extraplasmatic compartment.

Conclusion. Prolonged dialysis significantly reduces solute concentration levels, especially for those solutes that are distributed in a larger volume. Increasing both dialysis frequency and duration is the superior dialysis schedule.

Patients and Methods. Thirteen haemodialysis patients were converted from conventional (3 x 4 h/week) to an intensified nocturnal (3 x 8 h/week) dialysis and were longitudinally followed up for 12 months. Different parameters were evaluated before treatment conversion and quarterly during the follow-up period [i.e. dialysis efficacy (eKt/V), mean arterial pressure (MAP), antihypertensive drug score, extra-cellular volume (ECV), haemoglobin, transferrin saturation, ferritin, dose of erythropoiesis-stimulating agents (ESA), iron requirement, parameters of nutrition (body weight (BW), albumin, protein, normalized protein catabolic rate (nPCR), bioelectrical impedance analysis (BIA)), C-reactive protein, calcium–phosphate product, alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and amount of phosphate-binding pharmacotherapy].

Results. The calculated dialysis efficacy rose after switching the treatment mode (eKt/V 1.87 versus 2.7, P < 0.0001). Further, a significantly decreased MAP in the pre- (100 versus 89 mmHg) and postdialytic period (97 versus 83 mmHg), and a decreased ECV (13.8 versus 13.2 L; P = 0.03) even though antihypertensive pharmacotherapy could be substantially reduced (P < 0.0001), was found. Concomitant with a reduction of ESA (66.5 versus 45.2 IU/ kg/week; P = 0.006), the haemoglobin level rose significantly (11.4 versus 12.5 g/dL, P = 0.01). Nutritional status assessed by BW (70.9 ± 20.2 versus 72.1 ± 19.8 kg, P = 0.02), nPCR (1.39 versus 2.25 g/kg/day, P = 0.02) and BIA (phase angle: 6.2 versus 6.9°, P < 0.001) improved. The calcium–phosphate product slightly declined, without changes in the dose of any phosphate binders. Surprisingly, iPTH of those patients with intact parathyroid glands (n = 7) increased ~3-fold (27.9 versus 59.35 pmol/L, P = 0.009), while the AP was found stable.

Conclusion. This study demonstrates improvements in numerous dialysis-associated metabolic variables after intensification of HD time. Of note, an increase of iPTH was detected in those patients with intact parathyroid glands.

Methods. Leftover samples from 21 patients on maintenance HD as well as control samples from healthy volunteers (n = 3) were incubated at 4°C with small amounts of tPA (25 and 50 µL). In addition, pooled samples from HD patients with various PTH levels were incubated with 6.5, 12.5 and 25 µL of tPA and analysed with two different PTH assays with incubation times up to 48 h.

Results. A rapid decline of PTH values to 2.5–33.5% of the original baseline was observed after 24 h with a further decrease to <1–15% after 48 h. The two different assays gave very similar results when the samples were incubated with tPA.

Conclusion. Minimal contamination of a blood sample with tPA results in degradation of PTH in a time-dependent manner. The tPA is therefore unique as a contaminant since its enzymatic activity means that even tiny amounts of contamination will lead to major errors in PTH results by digestion of the protein. This phenomenon was independent of the assay used. Strict attention to the technique when drawing a blood sample from a catheter is mandatory to prevent contamination and avoid spurious test results.

Methods. During 15 haemodialysis treatments with a calcium-free dialysis solution, citrate was infused pre-dialyser and calcium was substituted post-dialyser. Systemic and extracorporeal citrate and calcium concentrations were repeatedly measured to calculate citrate and calcium pharmacokinetics.

Results. Removal by dialysis constituted the major elimination pathway of citrate (83 ± 5%). Systemic citrate load and concentrations were low (17 ± 7 mmol/4 h, 0.3 ± 0.15 mmol/l). Combined use of calcium-free dialysate and citrate infusion increased diffusible calcium to 80% of total calcium and induced substantial dialytic loss of calcium (43 ± 4 mmol/4 h). Since calcium was substituted, systemic calcium balances were positive (~+5 mmol) and concentrations stable. Calcium supplementation correlated with calcium dialytic losses, which in turn were dependent on total calcium and haematocrit.

Conclusions. When using calcium-free dialysate during citrate anticoagulation, hypocalcaemia is very likely unless calcium is re-infused, because large amounts of calcium are lost in the dialysate. However, an accumulation of citrate in the patient's systemic circulation is an unlikely cause of hypocalcaemia since most of the citrate is removed by dialysis. Calcium substitution and monitoring are the most important safety measures. We propose a rational approach based on haematocrit and total calcium for the choice of the starting calcium supplementation rate.

Methods. We examined 162 dialysis patients admitted to a single institute, including 8 patients with active TB, and evaluated the utility of this test in dialysis patients.

Results. Among 162 dialysis patients, positive QFT results occurred in 28 (17.3%), negative QFT results occurred in 95 (58.6%) and indeterminate QFT results occurred in 39 (24.1%). All eight active TB patients had positive QFT results, and none of the 95 patients with negative results had active TB. Among 23 patients with a history of active TB, 10 (43.5%) had positive results. Although the indeterminate rate was relatively high, no patient with an indeterminate result had active TB. Factors such as shorter duration of dialysis, lower lymphocyte count and higher white blood cell count were associated with indeterminate results. Among 105 cases after excluding the patients with previous TB or indeterminate results, the sensitivity of the QFT is 100% (8 of 8) and the specificity is 89.7% (87 of 97 cases).

Conclusions. Our data suggest that the QFT test is a useful supplementary tool for the diagnosis of active TB even in dialysis patients. Negative and indeterminate results on this test may be used to exclude the presence of active TB.

Methods. A Markov model was developed to estimate costs and health outcomes [survival (life years saved, LYS) and quality-adjusted survival (QALYs)] for the alternative strategies. Outcome data were obtained from a meta-analysis of randomized trials and large-scale renal registries.

Results. IL2Ra offers improved survival of 0.21 LYS (2.5 months) and 1.42 QALYs compared with no induction, with a cost saving over 20 years of $79 302 per patient treated regardless of risk profile. The incremental benefits of IL2Ra compared with polyclonal antibody induction therapy were 0.35 LYS (4.3 months) and 0.20 QALYs, with an incremental cost of $5144 per patient. The incremental cost-effectiveness ratio (ICER) of IL2Ra compared to polyclonal induction was $14 803 per LYS and $25 928 per QALY. Sensitivity analyses showed that IL2Ra remained more effective and less expensive than no induction. When IL2Ra was compared to polyclonal induction, the model was sensitive to changes in the cost of induction and the probability of malignancy. Over the range of all other variables tested, IL2Ra was cost-effective compared to polyclonal induction.

Conclusions. Adopting IL2Ra as induction immunosuppression for kidney transplant recipients improves survival and QALYs and is less costly than no induction. It also represents good value for money compared to polyclonal induction.

Methods. A 3-month pharmacokinetic substudy of the prospective, randomized, multicentre, open-label Symphony study was performed. Eighty-three adult renal transplant patients received standard-dose cyclosporine, MMF 2 g/day and corticosteroids, or daclizumab induction, MMF 2 g/day and corticosteroids plus low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus. The area under the concentration–time curve (AUC_0–12) of MPA and its metabolites between treatment groups was compared. Pharmacokinetic sampling was performed before MMF administration and at 20, 40, 75 min; 2, 3, 6, 8, 10 and 12 h post-d