Methods. RAW 264.7 cells were stimulated by LPS/IFN- in the absence and presence of PAA. iNOS mRNA was determined by real-time PCR, iNOS protein was examined by western blotting and the NO degradation product, nitrite, by Griess assay. Macrophage phagocytosis was assessed by FACS and fluorescence microscopy. Further we quantified the cytotoxicity against intracellular bacteria (Salmonella typhimurium) by a macrophage-killing assay. ELISA and Bioplex protein array system was used for the investigation of iNOS second messenger pathways (NF-B, ERK1/2, JNK and p38MAPK). iNOS mRNA half-lifetime in the presence or absence of PAA was determined by real-time PCR.

Results. PAA significantly inhibits iNOS mRNA induction in RAW 264.7 cells by LPS/IFN- [6 h: LPS/IFN--stimulation: 100%; LPS/IFN--stimulation/PAA (1 mM): 68 ± 7%] at concentrations comparable to those of patients on chronic haemodialysis. iNOS protein expression and nitrite formation in RAW 264.7 cells were significantly inhibited by PAA. iNOS mRNA half-lifetime was not affected by PAA. The phagocytic activity of RAW 264.7 was not significantly affected by PAA, whereas the cytotoxicity against intracellular bacteria was significantly reduced. Analysis of the iNOS signal transduction pathways provided evidence that activation of the mitogen-activated kinases ERK1/2 and JNK is significantly blocked by PAA, whereas activation of p38MAPK is unaffected. The NF-B pathway was not affected by PAA.

Conclusions. The present findings show that the uraemic toxin PAA has inhibitory effects on macrophage-killing function, which are mediated by inhibitory effects on transcriptional iNOS regulation. iNOS inhibition by PAA might affect immunoregulatory processes and could play a role in aggravation of immunodeficiency of patients with end-stage renal disease.

Methods. Peritoneal biopsies of 89 subjects (48 uraemic and 41 healthy age-matched patients) were examined. The expression of CD3, IL-6, activated NFBp65, VEGF, transforming growth factor (TGF)-β1, smooth-muscle actin (SMA), methylglyoxal (MGO) and RAGE was analysed immunohistochemically. Additionally, in 4 of the 48 uraemic patients, peritoneal biopsies were repeated after 15 months at the time of catheter removal to analyse the above parameters and the extent of NFB-binding activity determined by electrophoretic mobility shift assay (EMSA) in the long-term follow-up.

Results. In comparison to the healthy controls, uraemic patients showed a significant increase in fibrosis, angiogenesis, submesothelial thickness, MGO-derived protein adducts, RAGE, IL-6, VEGF, TGF-β1, SMA and NFBp65 in their peritonea. Four patients, followed up longitudinally from peritoneal dialysis (PD) catheter insertion to removal, demonstrated further significant increase in the above parameters, particularly in RAGE expression and NFB activation.

Conclusions. Along with a higher expression of several indicators for inflammation, angiogenesis, fibrosis and AGE accumulation, the peritoneal membrane of the uraemic patients showed an increased submesothelial thickness and a marked induction of RAGE expression and NFB-binding activity, which both further increased after PD treatment. These findings in human peritoneum support the concept of the AGE–RAGE interaction being crucial in peritoneal damage due to uraemia and PD.

Methods. At baseline, OPG and aortic pulse wave velocity (PWV) were measured in 98 chronic haemodialysis patients who were followed for a median of 24 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related cardiovascular mortality was evaluated by including both OPG and PWV in the same survival model.

Results. At baseline mean (standard deviation) PWV was 11.2 (3.3) m/s and median OPG (interquartile range) was 11.1 (7.5–15.9) pmol/L. There was a strong, positive, linear relationship between PWV and lnOPG (P = 0.009, model R² = 0.540) independent of covariates. During follow-up 23 patients died of cardiovascular causes. In separate univariate survival models both PWV and lnOPG were related to cardiovascular mortality [hazard ratios 1.31 (1.14–1.50) and 8.96 (3.07–26.16), respectively]. When both PWV and lnOPG were entered into the same model, only lnOPG remained significantly associated with cardiovascular mortality [hazard ratio 1.11 (0.93–1.33) and 7.18 (1.89–27.25), respectively).

Conclusion. In haemodialysis patients OPG is strongly related to PWV and OPG related cardiovascular mortality risk is, in part, mediated by increased PWV.

Methods. This multicentre, open-label study enrolled haemodialysis subjects (N = 444) with moderate to severe sHPT (mean serum biPTH > 160–430 pg/mL) (~iPTH 300–800 pg/mL or ng/L). Cinacalcet was titrated sequentially (30–180 mg/day) during an 8-week dose-titration phase to achieve biPTH ≤160 pg/mL (~iPTH 300 pg/mL or ng/L) and efficacy was assessed over 8 weeks. At week 2 of the study, subjects receiving vitamin D sterols had doses reduced to the equivalent of 2 mcg of paricalcitol three times a week or 6 mcg/week. Among the efficacy endpoints were the proportion of subjects with mean biPTH ≤160 pg/mL (~iPTH 300 pg/mL or ng/L), with mean Ca x P ≤55 mg²/dL² (4.4 mmol²/L²) and with both simultaneously during the assessment phase.

Results. The majority of subjects (n = 375) reached the assessment phase of the study and were included in efficacy analyses; 39 subjects withdrew due to adverse events. Sixty-two percent of subjects achieved the biPTH target, 83% achieved the Ca x P target and 54% reached both targets. Treatment reduced biPTH by 35% (P < 0.0001), calcium by 11% (P < 0.0001), phosphorus by 7% (P < 0.0001) and Ca x P by 17% (P < 0.0001). The proportion of subjects with values for biPTH, for Ca x P and for both biPTH and Ca x P within the target range during the assessment phase did not differ between subjects who received cinacalcet together with vitamin D sterols, and those who received cinacalcet alone.

Conclusion. Among subjects with moderate to severe sHPT undergoing haemodialysis, combined therapy with cinacalcet and low doses of vitamin D sterols improved achievement of the biochemical targets for CKD-MBD recommended by the KDOQI^TM guidelines.

Methods. MN was induced in BALB/c mice with intravenous injections of cationic bovine serum albumin. Three groups of mice were administered 100 µmol/kg Cobalt protoporphyrin (CoPP, a potent HO-1 inducer), Tin protoporphyrin (SnPP, a potent HO-1 inhibitor) or phosphate-buffered saline via intra-peritoneal injections once a week starting from the induction of MN. Disease severity was verified by serum and urine metabolic profiles and by renal histopathology. Cytokine profiles, immunoglobulin production, the expression of oxidative stress markers (thiobarbituric acid reactive substances, TBARS) and apoptosis, as measured by TUNEL, were also determined.

Results. Mice treated with CoPP displayed a significant reduction in proteinuria and a marked amelioration of glomerular lesions, accompanied by attenuated immune-complex deposition. The production of immunoglobulins in MN mice treated with CoPP was significantly reduced compared with that of mice in the other two groups. TBARS in the serum and kidneys, as well as apoptosis, were also significantly reduced in CoPP-treated mice. Cytokine mRNA expression in the renal cortex indicated that CoPP not only decreased the expression of proinflammatory cytokines, but also increased the expression of anti-inflammatory cytokines (interleukin-10).

Conclusions. HO-1 induction therapy may ameliorate experimental MN via multiple pathways, including anti-oxidative, anti-apoptotic and immunomodulatory effects. HO-1 inducing regimens should be considered as a potential therapeutic intervention in MN in the future.

Methods. Eighty-three patients were randomly assigned to either once-weekly epoetin alfa (n = 44) or their original dose twice- or thrice-weekly regimen (control, n = 39) for 12 weeks. The haemoglobin concentration was maintained within the target range of 9.0–12.0 g/dL by adjusting the dose of epoetin alfa. All patients received intravenous iron supplementation, as required.

Results. Stable haemoglobin levels were maintained without epoetin dose increases in the majority of patients in both groups (once-weekly group, 95.0%, control group, 91.4%). The mean haemoglobin levels at randomization at weeks 4, 8 and 12 were 10.7, 11.1, 11.3 and 11.0 g/dL, respectively, in the once-weekly group, and 10.5, 11.3, 11.5 and 11.3 g/dL, respectively, in the control group. The mean weekly dose of epoetin alfa at randomization at weeks 4, 8 and 12 was 142.8, 114.5, 108.6 and 104.5 IU/kg, respectively, in the once-weekly group, and 128.4, 116.0, 101.0 and 96.1 IU/kg/week, respectively, in the control group. No statistically significant between-group differences were apparent for changes in haemoglobin levels or epoetin alfa dosages at week 12.

Conclusions. This study demonstrates that once-weekly SC administration of epoetin alfa is as effective and safe as two or three times weekly administration in maintaining haemoglobin levels. Therefore, the once-weekly therapy using high dose of epoetin alfa is considered to be an efficient method in stable haemodialysis patients.

Design, participants and methods. In a prospective study with 27 patients, we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation. Genomic damage was measured by the frequency of micronuclei, a subset of chromosomal aberrations, in PBL.

Results. Supplementation with folic acid and vitamin B12 (more markedly with both) reduced the micronucleus frequency in PBL of dialysis patients. This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation. Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation, and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N⁶-etheno-2'-deoxyadenosine, a marker for oxidative stress.

Conclusions. A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12. This may be mediated by Hcy reduction.

Methods. Primary human umbilical venous endothelial cells (HUVEC) and primary human glomerular microvascular endothelial cells (GMVEC) were incubated for 24 h with a subtoxic dose of Stx1 or Stx2. Then, cells were treated with heparan sulfate-degrading enzyme heparitinase I or left untreated, followed by determination of binding leukocytes to endothelial cells in a parallel plate flow chamber.

Results. In both cell types, Stx increased the amount of firmly adherent leukocytes. After removal of endothelial heparan sulfate, the number of adhering leukocytes decreased.

Conclusions. HSPG have a distinctive role in adhesion of leukocytes to endothelial cells stimulated by a subtoxic dose of Stx.

Methods. Adult male Wistar rats were divided into four groups: sham (sham operated); sham operated + 440 mg/kg body weight (BW) of NAC daily in drinking water, started 2 days before and maintained until 48 h after the surgery; BUO (24-h BUO only); BUO + NAC-pre (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started 2 days before BUO); and BUO + NAC-post (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started on the day of BUO relief). Experiments were conducted 48 h after BUO relief.

Results. Serum levels of thiobarbituric reactive substances, which are markers of lipid peroxidation, were significantly lower in NAC-treated rats than in the BUO group rats. The administration of NAC provided significant protection against post-BUO GFR drops and reductions in RBF. Renal cortices and BUO rats presented decreased eNOS protein expression of eNOS in the renal cortex of BUO group rats, whereas it was partially recovered in BUO + NAC-pre group rats. Urine osmolality was significantly lower in BUO rats than in sham group rats or NAC-treated rats, the last also presenting less interstitial fibrosis. Post-BUO downregulation of AQP2 protein expression was averted in the BUO + NAC-pre group rats.

Conclusions. This study demonstrates that NAC administration ameliorates the renal function impairment observed 48 h after the relief of 24-h BUO. Oxidative stress is important for the suppression of GFR, RBF, tissue AQP2 and eNOS in the polyuric phase after the release of BUO.

Methods. Based on three prospective urine samples in an unselected nonhypertensive, nondiabetic HIV-positive cohort (n = 495), we analysed the prevalence of microalbuminuria and compared the Caucasian share with that of a nonhypertensive, nondiabetic population-based control group (n = 2091). Significant predictors for microalbuminuria were analysed within the HIV-positive cohort.

Results. The prevalence of microalbuminuria was 8.7% in the HIV-infected cohort, which is three to five times higher than that in the general population. HIV-infected patients with microalbuminuria were older, and had higher blood pressure, longer duration of HIV infection, higher serum beta 2-microglobulin, higher serum creatinine and a reduced glomerular filtration rate of ≤90 mL/min, compared with those with normal albumin excretion. In multivariate analysis, systolic blood pressure, serum beta 2-microglobulin and duration of HIV infection were found to be independent predictors of microalbuminuria.

Conclusions. Our findings indicate that in addition to haemodynamic effects, inflammatory activity may be implicated as a cause of the development of microalbuminuria. With respect to the increasing risk of developing CVD or renal diseases and mortality, the high prevalence of microalbuminuria in HIV-infected individuals warrants special attention.

Methods. PCR and direct sequencing of PVALB was performed in 132 GS patients in whom only one or no (N = 79) mutant SLC12A3 allele was found. The possible interference of biallelic SNPs (single nucleotide polymorphisms) on normal transcription or normal splicing was investigated. Genotyping of 110 anonymous blood donors was performed to determine the allelic frequency in the normal population.

Results. No sequence variants resulting in amino acid substitution or truncated protein within the PVALB gene were found in the 264 chromosomes tested. Ten biallelic SNPs, including six novel polymorphisms, were identified: five in the 5' UTR, none of them affecting predicted regulatory elements; three in the coding region, without alteration of the consensus splice sites, and two in the 3' UTR. The observed allelic frequencies did not differ significantly between GS patients and controls.

Conclusion. Our results strongly suggest that mutations in the PVALB gene are not involved in GS patients who harbour a single or no mutant SLC12A3 allele.

Methods. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures.

Results. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, ß = –0.45, model R² = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, ß = –0.29 and P = 0.014, ß = 0.33, respectively, model R² = 32%).

Conclusions. This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment.

Methods. A well-defined model of nephrotoxicity in salt-depleted male rats was used. Monotherapy groups were distributed as a non-treated control group with saline solution (n = 12), the Tac group (n = 16) (tacrolimus 6 mg/kg/day) and the CsA group (n = 13) (CsA 15 mg/kg/day). The groups with different associations were scattered as the Tac + SRL group (n = 14) (tacrolimus 6 mg/kg/day and rapamycin 3 mg/kg/day) and the CsA + SRL group (n = 7) (CsA 15 mg/kg/day and rapamycin 3 mg/kg/day). Groups were divided into 30 and 70 days of follow-up, but the CsA + SRL group was only studied for 30 days because animals became sick.

Results. Rats with the CsA + SRL association were the only ones which showed a significant reduction in body weight, impairment of renal function and severe and diffuse tubular vacuolization and tubular atrophy following a striped distribution, and scarce areas of the kidney were still preserved. The Tac + SRL association did not produce renal function impairment, and mild histological damage including enhanced periglomerular tubular atrophy was observed. This local damage affected the distal convoluted tubule involving macula densa and juxtaglomerular apparatus. Pro-inflammatory mediators paralleled functional and structural data. ED-1 and TNF- were noticeably higher in the CsA + SRL than in the Tac + SRL association. Only in the CsA + SRL association an important increase in -SMA+ cells was seen, mainly found in the areas with tubular atrophy. TGF-β1 was also markedly enhanced in the CsA + SRL association whilst monotherapy or Tac + SRL groups at 30 days TGF-β1 did not show any changes. However, at 70 days of treatment TGF-β1 was significantly increased in the Tac + SRL group. Animals receiving SRL showed a decrease in renal vascular endothelial growth factor (VEGF) expression. This growth factor was significantly down-regulated in both CNI associations than in SRL monotherapy. P-glycoprotein (Pgp) was overexpressed in CsA and CsA + SRL therapy whilst Tac and TAC + SRL showed a middle increase Pgp expression but higher than the control and SRL group.

Conclusion. We conclude that the association of SRL with high doses of CsA or Tac produces a different functional, histological, inflammatory and pro-fibrogenic pattern. Thus, the addition of SRL to high doses of CsA leads to severe renal injury. Combination with high doses of Tac is clearly less deleterious in the short term. However, there is a low grade of pro-fibrotic inflammatory expression when this association is prolonged.

Methods. We retrospectively reviewed laboratory and demographic data from 1499 patients receiving hemodialysis in 15 units operated by the same dialysis provider. We performed univariate and multivariate logistic regression analysis to determine predictors of an average 3-month hemoglobin level below or above the target interval of 11.0–12.5 g/dL. To explain the effect of facility on anemia performance, we calculated correlations between measures of EPO responsiveness and the probability of achieving the target interval by facility.

Results. Patients above the target hemoglobin range demonstrated an association with parathyroid hormone (PTH) (OR = 0.96 per 100 pg/mL increase), female gender (OR = 0.68), EPO protocol use (OR = 0.94 per 10% increase in use) and facility (range of OR = 0.26–2.59 for 15 participating sites). Patients below the target hemoglobin range demonstrated an association with CRP (OR = 1.10 per mg/L increase), PTH (OR = 1.07 per 100 pg/mL increase), iron deficiency (OR = 1.07 per 10% increase), EPO protocol use (OR = 0.89 per 10% increase in use), iron protocol use (OR = 0.93 per 10% increase in use) and facility (range of OR = 0.58–3.41 over 15 units). EPO index (r = 0.71), EPO dose (r = 0.73), hemoglobin (r = –0.60) and EPO per unit weight (r = 0.76) were significantly correlated with the probability of achieving the target hemoglobin by facility.

Conclusions. The facility significantly influences the outcome of anemia management in patients with ESRD. In part, this is due to the patients’ EPO responsiveness, which may be influenced by facility care patterns.

Methods. In this cross-sectional study, we estimate the prevalence of abnormal glucose metabolism (AGM) using oral glucose tolerance test (OGTT) and identify its predictive factors. Patients who received kidney transplantation in our centre without pre-transplant diabetes were recruited. OGTT was performed in patients with fasting glucose levels between 5.6 and 6.9 mmol/L for at least two occasions 6 months post-transplantation.

Results. Of 119 patients recruited, 31 had OGTT performed. The prevalence of PTDM, IGT and IFG was 21.8 (26/119)%, 6.7 (8/119)% and 3.4 (4/119)% respectively. Thus the overall prevalence of AGM was 31.9%. Age (P = 0.003), body mass index (P = 0.032), hepatitis B seropositivity status (P = 0.01), CMV infection (P = 0.02) and acute rejection (P = 0.002) were all associated with development of AGM. Using multivariate analysis, only older age at transplant (OR 1.09), history of acute rejection (OR 3.40) and hepatitis B seropositivity (OR 3.13) were significantly associated with the development of AGM.

Conclusion. AGM is common in our renal transplant recipients.

Methods. We investigated the effect of some lysophospholipids on the nucleation, extension and stabilization of Aβ2M amyloid fibrils at a neutral pH, using fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy and electron microscopy. We also measured plasma concentrations of lysophospholipids in 103 haemodialysis patients and 14 healthy subjects and examined the effect of uraemic and normal plasmas on the stabilization of Aβ2M amyloid fibrils at a neutral pH.

Results. Some lysophospholipids, especially lysophosphatidic acid (LPA), induced not only the extension of Aβ2M amyloid fibrils but also the formation of Aβ2M amyloid fibrils from the β2-m monomer at a neutral pH, by partially unfolding the compact structure of β2-m to an amyloidogenic conformer as well as stabilizing the extended fibrils. Haemodialysis patients had significantly higher plasma concentrations of LPA than healthy subjects. Furthermore, uraemic plasmas with the highest ranking LPA concentrations stabilized Aβ2M amyloid fibrils significantly more potently than normal plasmas. On the other hand, simple addition of LPA to normal plasma did not enhance the fibril stabilizing activity.

Conclusions. These results suggest a possible role of lysophospholipids in the development of Aβ2M amyloidosis.

Methods. The PAI-1 genotype was determined for both the 304 donors and the 337 corresponding recipients. In recipients, PAI-1 antigen levels were also determined. We compared 4G/4G donors versus donors with other genotypes.

Results. Donor or recipient genotype did not influence the PAI-1 plasma level in recipients. Actuarial kidney graft survival was significantly reduced in the 4G/4G donor group (107 months versus 147.5 months, P = 0.013), while recipient PAI-1 genotype did not show any influence on graft survival. Moreover, graft loss due to IFTA proved significantly higher in the 4G/4G donor group (13% versus 6%, P = 0.03). Multivariate analysis showed that the significant independent variables associated with graft loss were the donor 4G/4G genotype, acute clinical rejection and donor age.

Conclusion. Our study suggests that donor PAI-1 polymorphism influences kidney graft survival and that the donor 4G/4G genotype is an independent risk factor for graft loss. Prospective studies are needed to confirm these results.

Purpose. The purpose of this study is to determine the extent to which fibroblast-specific protein 1-positive (FSP1⁺) cells are predictive of corticosteroid responsiveness in patients with IgAN.

Patients and Method. Fifty biopsy-proven IgAN patients who received corticosteroid therapy were enrolled and followed for 7.1 ± 3.0 years. FSP1⁺ cells were identified using an anti-FSP1 antibody.

Result. Twelve patients showed progression of renal impairment or no reduction of urinary protein (non-responders) after steroid therapy. In the remaining 38 patients, renal function was stable during follow-up, and their urinary protein declined to <1.0 g/day (responders). Serum creatinine, estimated GFR, severity of mesangial proliferation, percent glomerulosclerosis/total glomeruli, extent of interstitial damage and FSP1⁺ cell number were all significantly higher in non-responders than in responders. Cox regression analysis using two covariates with every possible combination of factors indicated that FSP1⁺ cell number was the strongest and most significant predictor of corticosteroid responsiveness. When IgAN patients had >32.6 FSP1⁺ cells/HPF at diagnosis, they were the more likely to show steroid resistance.

Conclusion. FSP1⁺ cell number can serve as an excellent predictor of corticosteroid responsiveness in patients with IgAN.

Methods. CsA-treated mice were injected with recombinant adenovirus expressing either COMP-Ang1 or LacZ. Histology, inflammatory, haemodynamic and fibrotic parameters, and signalling pathway were evaluated.

Results. Histologic examination showed that COMP-Ang1 significantly decreased CsA-induced tubular damage and tubulointerstitial fibrosis. CsA-induced increases in macrophage infiltration and expression of MCP-1 and ICAM-1 after CsA treatment were significantly reduced by COMP-Ang1. Treatment with COMP-Ang1 also decreased the CsA-induced increases in TGF-β1 and Smad 2/3 levels while increasing Smad 7 levels. Laser–Doppler sonographic findings and endothelial factor VIII staining revealed that COMP-Ang1 preserved the integrity of peritubular vasculature and intrarenal haemodynamics from the CsA-induced renal injury. COMP-Ang1 inhibited tubular cell apoptosis while increasing tubular cell proliferation in CsA-induced renal injury.

Conclusions. These results indicate that COMP-Ang1 exhibited a protective effect on damaged peritubular capillaries, haemodynamic alteration and inflammation in CsA-induced renal injury. Thus, COMP-Ang1 may be useful as a therapeutic and prophylactic agent for specific protection against endothelial dysfunction and inflammation.

Methods. This was a retrospective cohort study. Of 850 IgA nephropathy (IgAN) patients that were followed up in our renal centre, 32 received MMF (1–1.5 g/day) and 47 were treated with cyclophosphamide (CTX; 50–100 mg/day). All the patients also received prednisone. SP was defined as diffuse bilateral lung infiltrate with respiratory failure, and PCP was diagnosed by detecting organisms in sputum and bronchoalveolar lavage.

Results. Patients given MMF or CTX did not differ in their distribution of age, sex, renal function or prednisone dosage. However, 6 of the 32 patients developed SP around the third month after the initiation of MMF administration: 3 were diagnosed with PCP, 2 with suspected PCP and in the other PCP could not be excluded. SP did not occur in patients treated with CTX. Most SP cases (five of six) presented with abrupt onset and rapidly progressed to respiratory failure, from which four died. The deterioration of renal function was strongly associated with the occurrence of SP. Six patients (6 of 16) with chronic renal function impairment (eGFR < 60 ml/min/1.73 m²) developed SP while none of the patients with eGFR > 60 ml/min/1.73 m² did. Absolute lymphocyte counts decreased significantly in patients with eGFR < 60 ml/min/1.73 m² after 3 months of MMF treatment compared to the counts before MMF was initiated (1.71 ± 0.23 versus 2.43 ± 0.17 x 10⁹/l, P = 0.04). This effect was more pronounced in patients with SP, which had significantly lower counts than patients without SP (0.22 ± 0.04 versus 1.91 ± 0.20 x 10⁹/l, P = 0.001). The occurrence of SP or PCP in patients with chronically impaired renal function was also associated with lymphopenia.

Conclusions. This study is the first report of delayed SP including PCP following MMF plus corticosteroids in patients with IgAN. Chronically impaired renal function might be a risk factor for severe infection, and lymphocyte counts may serve as useful and convenient tools for monitoring the intendance of the occurrence of PCP. This finding and its risk factors need to be further evaluated.

Methods. We examined the excretion of viable PDX-positive cells in a random set of spot urine from patients with biopsy-proven focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MGN) or membranoproliferative glomerulonephritis (MPGN) and characterized the excreted cells for podocyte and parietal epithelia markers as well as for proliferation activity.

Results. We found that untreated patients with active disease excrete high numbers of PDX-positive cells in their urine. In contrast to that we were not able to detect significant amounts of PDX-positive cells in the urine of patients with active minimal change disease (MCD) and patients with FSGS or MGN in full remission. When we further characterized the cells we rarely detected expression of podocyte specific markers in the PDX-positive cells, but at least 50% of the PDX-positive cells were double positive for cytokeratin (CK8–18). Immunohistochemistry of the corresponding renal biopsies showed that 100% of podocytes and parietal cells stained positive for PDX. Semiquantitative analysis revealed that 45% of parietal cells were positive for CK8–18 and 100% of proximal tubular cells. No cells of the glomerular epithelial layer stained positive for CK8–18.

Conclusions. PDX-positive cells are lost in the urine in disease states that require podocyte regeneration and are a useful non-invasive marker for glomerular disease activity. These cells are possibly derived from the parietal epithelial layer.

Methods. A new bioimpedance spectroscopy device (BCM—Body Composition Monitor) was selected that allows quantitative determination of the deviation in hydration status from normal ranges (HS). Pre-dialysis systolic blood pressure (BPsys) and HS was analysed in 500 haemodialysis patients from eight dialysis centres. A graphical tool (HRP—hydration reference plot) was devised allowing HS to be combined with measurements of BPsys enabling comparison with a matched healthy population (n = 1244).

Results. Nineteen percent of patients (n = 95) were found to have normal BPsys and HS in the normal range. Approximately one-third of patients (n = 133) exhibited reasonable control of BPsys and fluids (BPsys <150 mmHg and HS <2.5 L). In only 15% of patients (n = 74) was hypertension observed (BPsys >150 mmHg) with a concomitant HS >2.5 L (possible volume-dependent hypertension). In contrast, 13% of patients (n = 69) were hypertensive with HS <1.1 L (possible essential hypertension). In 10% of patients (n = 52), BPsys <140 mmHg was recorded despite HS exceeding 2.5 L.

Conclusion. Our study illustrated the wide variability in BPsys regardless of the degree of HS. The HRP provides an invaluable tool for classifying patients in terms of BPsys and HS and the proximity of these parameters to reference ranges. This represents an important step towards more objective choice of strategies for the optimal treatment of hypertension and FO. Further studies are required to assess the prognostic and therapeutic role of the HRP.

Methods. One hundred and fifty patients were treated in-centre, most because of medical complications and 265 by home or self-care haemodialysis. Patients were on daily haemodialysis for 29 ± 31 (0–272) months. Forty-two percent had primary and 31% had secondary renal failure. Treatment time was 136 ± 35 min, frequency 5.8 ± 0.5 times/week and weekly stdKt/V 2.7 ± 0.55.

Results. Eighty-five patients (20%) died; 5-year cumulative survival was 68 ± 4.1% and 10-year survival was 42 ± 9%. Age, secondary renal failure and in-centre dialysis were associated with mortality, while gender, frequency of dialysis (5, 6 or 7 per week), continent, country and blood access were not. Survival was compared with matched patients from the USRDS 2005 Data Report using the standardized mortality ratio and cumulative survival curves. Both comparisons showed that the survival of the daily haemodialysis patients was 2–3 times higher and the predicted 50% survival time 2.3–10.9 years longer than that of the matched US haemodialysis patients. Survival of patients dialyzing daily at home was similar to that of age-matched recipients of deceased donor renal transplants.

Conclusions. Survival of patients on short daily haemodialysis was 2–3 times better than that of matched three times weekly haemodialysis patients reported by the USRDS.

Methods. Of a cohort of 425 patients, 226 survivors with severe AKI necessitating renal replacement therapy (RRT) were followed up for 60 months after hospital discharge. None of these patients had pre-existing kidney disease. Vital status and renal function were documented annually for 5 years.

Results. None of the discharged or transferred patients was dependent on RRT; 57% had complete recovery and 43% had partial recovery of renal function. During the first year after hospital discharge, 18% of survivors died, during the second year 4% and during the third to fifth year 2% per year. At 5 years, 25% of the cohort were still alive. Further improvement in renal function (eGFR) was noted in 26 patients within the first year only. Deterioration of renal function occurred in eight patients. At 5 years, renal function was normal in 86% of the remaining survivors, it was impaired in 9% and 5% of the patients alive needed dialysis again. The proportional Cox regression analysis model showed that pre-existing extrarenal comorbidity, surgery and partial recovery of renal function were independent determinants of long-term survival.

Conclusions. This prospective observational study indicates that severe AKI is not only a determinant of excess in-hospital case fatalities of critically ill patients, but it also carries significant implications for long-term mortality.

Methods. 50 patients were randomized to either 2.27% glucose or icodextrin (n = 28) for a long exchange following a month run in. Blood samples were obtained at –1, 0, 3 and 6 months, coincident with measurements of urine volume and fluid status.

Results. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = –0.46, P = 0.007, in patients randomized to icodextrin, but not glucose. There were no relationships between fluid status and any inflammatory markers at any point of the study, with the exception of albumin at baseline, r = –0.39, P = 0.007. Amylase activities at –1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated; the only predictor of between-patient variability on multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily ultrafiltration, urine volume, fluid or inflammatory status.

Conclusions. This analysis supports observational data that changes in fluid status are associated with changes in urine volume. Icodextrin was not associated with a greater fall in urine output despite its larger effect on ECFv. Changes in fluid status could not be explained or did not appear to influence systemic inflammation. Nor can they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.

Methods. Thirty-three patients with CKD not yet on dialysis underwent an HRCT scan at baseline and 1 year to assess for CAC and CAC progression. Two radiologists independently reviewed films and each radiologist re-reviewed a randomly selected subset of films they had previously viewed, to assess for inter-reviewer and intra-reviewer reliability, respectively. Patients underwent a repeat scan within 30 min of the first baseline scan to assess for inter-scan reproducibility.

Results. At baseline, eight patients (24%) had no CAC. Of the 25 patients (76%) with CAC, 10 (40%) had severe calcification. Intra-reviewer agreement was 83%. Inter-reviewer agreement ranged between 77 and 94%. Six (27%) of the patients with >30 baseline CACS had >15% change in CACS following repositioning. Four of these patients had an increase in CACS with position change [18% (95% CI: 5–40%)]. Of the 21 patients who underwent a follow-up scan at 1 year, 7 (33%) demonstrated CACS progression.

Conclusions. There is significant imprecision in HRCT-derived CACS in CKD patients. This suggests a need for standardization of methods of CACS measurement with HRCT.

Methods. We conducted a multicentre, double-blind, prospective, parallel-group non-inferiority study of 885 hypertensive [systolic blood pressure/diastolic blood pressure (SBP/DBP) >130/80 mmHg] patients with T2D, proteinuria (≥900 mg/24 h) and serum creatinine (≤3.0 mg/dl) who were randomized to once-daily telmisartan 80 mg or valsartan 160 mg; additional antihypertensive therapy was permitted. The primary endpoint was the change from baseline in the 24-h proteinuria after 12 months. Secondary endpoints included changes in 24-h albuminuria, estimated glomerular filtration rate (eGFR) and inflammatory parameters asymmetrical dimethylarginine (ADMA), high-sensitivity C-reactive protein (CRP) and urinary 8-iso-prostaglandin F₂ (8-iso-PGF₂).

Results. Telmisartan and valsartan produced comparable reductions in 24-h urinary protein excretion rates: geometric mean reduction (95% confidence interval) [telmisartan, 33% (27–39%); valsartan, 33% (27–38%)]. No significant differences between treatments were seen in changes from baseline in 24-h urinary albumin excretion rate and eGFR at 12 months. With both treatments, greater renoprotection was seen among patients with better blood pressure control. No significant changes in ADMA or CRP were noted in either group after 12 months, but urinary 8-iso-PGF₂ levels decreased by 14% with telmisartan and by 7% with valsartan (P = 0.040).

Conclusions. In patients with T2D, hypertension and overt nephropathy, the renoprotection afforded by telmisartan and valsartan appears similar, and the study was unable to show any effect beyond that due to blood pressure control. At doses used to treat hypertension, there is no evidence of inflammatory parameters being modified by ARBs in patients with more advanced kidney disease due to T2D.

Methods. This was an observational cohort study (n = 35 529), mean age 75.7 years (SD = 5.3), of participants in the Elderly Health Examination Program (EHEP) in Kaohsiung City, Taiwan, between 2002 and 2004. Estimated glomerular filtration rate (eGFR) was calculated by the simplified modified diet in renal disease equation. Proportional hazard ratios (HR) of mortality associated with late-stage CKD were assessed by Cox regression.

Results. The crude prevalence rate of CKD stages 3–5 was 39.4%; 1840 participants (5.18%) died within 2-year follow-up, a mortality rate of 20.3 per 1000 person-years overall and 16.4 per 1000 person-years in the reference group. Higher HR for all-cause and cause-specific mortality were found in the groups with decreased eGFR. Compared with the reference group (eGFR > 60 mL/min/1.73 m²), adjusted HR for all-cause mortality were 1.5, 2.1 and 2.6 for groups with eGFR 30–44, 15–29 and < 15 mL/min/ 1.73 m², respectively (P < 0.001). Higher HR of mortality due to cardiovascular or renal diseases were also significantly associated with decreased eGFR (P < 0.05).

Conclusion. Late-stage CKD is a significant risk factor for mortality, especially due to cardiovascular and renal diseases, in elderly Taiwanese. Given the higher prevalence rate of late-stage CKD in the study area, CKD patient mortality was relatively lower, which might reflect underestimation of renal function for patients at early stages of CKD, or partly explain the high ESRD population.

Methods. Six-month-old female NZB/W F₁ mice with active nephritis (albuminuria >100 mg/dL) were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 4 months. The effect of rapamycin on the severity of nephritis was evaluated by clinical manifestations, biochemical parameters, renal histology, immunohistochemistry and semi-quantitative gene expression studies.

Results. Treatment with rapamycin significantly decreased albuminuria, improved survival, diminished splenomegaly, preserved renal function and reduced serum anti-dsDNA antibody levels. Kidney sections from saline-treated mice revealed marked mesangial proliferation, tubular dilation with intra-tubular protein cast deposition and leukocytic infiltration of the interstitium. The rapamycin-treated mice, in contrast, had relatively mild histological changes in their kidneys. Rapamycin treatment also significantly reduced the amount of immune complex deposition in the glomeruli, suppressed the interstitial infiltration by T-cells, B-cells and macrophages as well as down-regulated the intra-renal expression of RANTES.

Conclusions. We conclude that rapamycin is effective in attenuating the severity of established nephritis in NZB/W F₁ mice_. The beneficial effects of rapamycin are mediated, at least in part, through inhibition of lymphoproliferation, reduced RANTES expression and decreased inflammatory cell infiltration in the kidneys. Rapamycin could be of therapeutic value in the treatment of human lupus nephritis.

Methods. Patients with chronic kidney disease (CKD) were purposively sampled from four kidney dialysis and transplant centres in Australia to participate in nine focus groups (three each for pre-dialysis, dialysis and transplant patients), which were conducted from July 2006 to September 2006. Each involved 6–8 participants. Transcripts were coded and thematically analysed to identify recurrent research topics and the participants’ reasons for their choices.

Results. Participants suggested eight research priorities: prevention of kidney disease, better access to and improvement in kidney transplantation, reduction of symptoms of CKD and complications associated with treatment, new technological therapies, psychosocial aspects of living with CKD, whole body not organ-specialized care, and improvement in dialysis and caregiver support. Five major reasons for the selections were identified: normalization of life (developing therapies and regimens that fit into daily living), altruism (considering the welfare of others before personal needs), economic efficiency (channelling resources for maximum economic gain), personal needs (preferences based on feelings, values, personal needs) and clinical outcomes (improving health states and the physiological condition of patients with CKD).

Conclusions. A patient-focused research agenda is possible to elicit for CKD, and by inference for other healthcare issues. Unlike researchers who focus on specific interventions and questions, consumers think in terms of broad themes and quality of life outcomes. Effective methods for translating a patient-focused agenda into research priority setting and resource allocation are now needed.

Methods. Peritoneal dialysate and serum samples were obtained from 18 patients on PD, and western blot analysis using an antibody to oxidized protein was carried out with reprobing for albumin. Oxidized protein/albumin ratios were determined and compared with various clinical and laboratory variables including peritoneal equilibration test results.

Results. Oxidized protein/albumin ratios were higher in the dialysate of patients who were high/high average transporters compared to low/low average transporters. Oxidized protein ratios were also found to be higher in the dialysate of patients who had diminished urine output as a reflection of loss of residual renal function. Negative correlations were noted between oxidized protein ratios in the dialysate and serum albumin levels and creatinine clearance.

Conclusions. Higher levels of oxidized protein in the dialysate appear to be correlated with high/high average peritoneal membrane transport characteristics and may be related to loss of residual renal function. These preliminary findings suggest that it is plausible that oxidized proteins in the dialysate might play a contributory role in complications including membrane damage and ultrafiltration failure in patients on PD.