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. Separate groups of mice were given AAI (10 mg/kg and 20 mg/kg) or pretreatment with 3-methylcholanthrene (3-MC, an agent known to induce P450 1A expression in many species including rodents) at 60 mg/kg given at 24 h before AAI injection. Renal function and histopathology were determined at the 3rd day following the high dose of AAI and at the 14th day following the low dose of AAI treatment. For both doses, we determined in vivo AAI clearances and pharmacokinetic parameters. We also determined in vitro P450 1A1/2 activity and the ability of liver microsomes from 3-MC-treated and vehicle-treated mice to metabolize AAI. Finally, the effect of 3-MC on protein levels of P450 1A1/2 in both liver and kidney was measured by western blotting.

Results. Pretreatment with 3-MC greatly protected mice against renal failure induced by AAI. In vivo AAI clearance was more rapid in 3-MC-pretreated mice than in the vehicle-pretreated mice. In addition, the P450 1A1/2 activity and the ability to metabolize AAI in hepatic microsomes isolated from 3-MC-treated mice were much greater than in vehicle-treated mice. Western blotting showed that protein levels of hepatic P450 1A1/2 were greatly increased in 3-MC-treated mice than in vehicle-treated mice.

Conclusion. These results demonstrated that the induction of hepatic P450 1A1/2 protected against AAI-induced kidney injury through faster in vivo clearance of AAI and suggested an important role for hepatic P450s in the detoxification of AAI-induced renal injury.

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. 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.

Method. Cellular viability of PMNs, isolated from healthy volunteers, was tested by ATP chemiluminescence levels under MGO and/or H₂O₂, or 4-β phorbol 12-β-myristate 13--acetate (PMA). Superoxide anion (O₂^–) generation and apoptosis were measured by the reduction of ferricytochrome C and fluorocytometric analysis, respectively. Plasma MGO levels were measured by mass spectometry in 29 CKD patients.

Results. At low levels of MGO (1–10 µM) and H₂O₂ (12.5 µM), no differences were found in cellular viability as compared to controls, whereas their combination significantly decreased PMN viability. PMA stimulation enhanced cellular injury of MGO by a function of MGO levels and preincubation with 5,5-dimethyl-1-pyrroline-N-oxide (free radical trap agent) attenuated it. MGO suppressed O₂^– generation by PMA, while it accelerated apoptotic ratios in PMNs. Significant increases of plasma MGO and C-reactive protein levels were found by a function of CKD stage, and clinical level of MGO could induce PMN injury in combination with H₂O₂.

Conclusion. These results indicate the combinatory effect of MGO and H₂O₂ on PMN oxidative injury, and this pathology may be linked to enhanced oxidative stress in CKD.

Methods. Male Wistar rats underwent MI, sham MI, 5/6NX, or 5/6NX and MI. Six weeks later, the NX rats were treated with an angiotensin-converting enzyme inhibitor (ACEi) or vehicle for 6 weeks.

Results. An MI did not significantly induce more proteinuria (303 ± 46 versus 265 ± 24 mg/24 h) and glomerulosclerosis (40 ± 11 versus 28 ± 4 arbitrary units) in 5/6NX+MI compared to 5/6NX, and ACEi therapy was equally effective in reducing renal damage in these groups. In the 5/6NX+MI group, decreased renal blood flow and creatinine clearance were observed compared to 5/6NX (2.2 ± 0.6 versus 3.6 ± 0.4 ml/min/kg and 2.1 ± 0.3 versus 2.9 ± 0.3 ml/min/kg), which both increased after ACEi to levels comparable found in the group that underwent 5/6NX alone.

Conclusions. MI does not further deteriorate structural renal damage induced by 5/6NX compared with 5/6NX alone. Furthermore, renal haemodynamic impairment occurs after MI, which can be improved applying ACEi therapy. Therefore, we conclude that treatment with ACEi should be optimized in patients with chronic kidney disease after MI to improve renal function.

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. 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.

Materials. Samples were collected from 16 anti-GBM antibody-positive patients who were admitted to our department or related hospitals from December 1990 to October 2005. We analysed clinical and laboratory data, kidney biopsy findings, and the HLA-DR phenotypes and HLA-DRB1 alleles of the patients.

Results. Among the 16 patients, 15 had HLA-DR15 [the phenotype frequency (PF) was 93.8%], 7 were positive for DR4 (the PF was 43.8%) and 5 were positive for DR9 (the PF was 31.3%). The allele frequency of HLA-DRB1^*1501 was 46.4% (13/28), which was significantly different from Japanese controls (11.6%) (P < 0.001). In contrast, the frequency of HLA-DRB1^*1502 was not different from controls (0/28). The odds ratio of HLA-DRB1^*1501 in these patients was 6.4 (95% CI: 2.4–16.5).

Conclusion. The present study demonstrated that Japanese patients with anti-GBM antibody-mediated disease are very likely to carry the HLA-DRB1^*1501 but not the HLA-DRB1^*1502 allele.

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. 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. We analysed seven podocyte genes known to cause proteinuria and FSGS in a group of 19 non-familial childhood-onset steroid-resistant FSGS patients. These genes include NPHS1, NPHS2, ACTN4, CD2AP, WT-1, TRPC6 and PLCE1. We also screened for the mitochondrial A3243G DNA transition associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), and occasionally FSGS.

Results. No mutations were found in the ACTN4 and TRPC6 genes, and no mitochondrial A3243G DNA transition was found in our group of patients. Two patients showed mutations in the CD2AP gene, one combined with an NPHS2 mutation. A tri-allelic hit was found in a patient carrying compound heterozygous NPHS2 mutations and a heterozygous NPHS1 mutation. In another patient a de novo WT-1 mutation was found combined with a heterozygous NPHS1 mutation, and finally two patients showed three heterozygous PLCE1 mutations.

Conclusions. In our rather small group of 19 steroid-resistant FSGS patients, we found 11 mutations in podocyte genes in 6 patients. In four of them the found mutations could explain the pathology. Our data suggest that combined gene defects in podocyte genes may play a role in the development of FSGS.

Methods. 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.

Results. 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. We have studied 40 patients (27 males, 13 females) with iMN. The mean age was 48 ± 15 years, serum creatinine concentration 89 ± 17 µmol/l and proteinuria 8.9 ± 5.0 g/24 h. Urinary L-FABP and H-FABP were measured by ELISA. Renal failure was defined as an increase in serum creatinine >25% from baseline with a serum creatinine >135 µmol/l or an increase >50% from baseline. Urinary L-FABP excretion was detectable in all but one patient. The median (range) level was 3.29 (0.7–165.6) µg/mmol creatinine (normal <0.38 µg/mmol Cr). Urinary H-FABP was undetectable in nine patients. Median level was 1.53 (0.1–90.5) µg/mmol Cr (normal <0.1 µg/mmol Cr). Both L- and H-FABP correlated with urinary β2-microglobulin, urinary 1-microglobulin and IgG. Urinary H-FABP paralleled L-FABP.

Results. After a mean follow-up of 75 ± 32 months, 16 (40%) patients have reached the predefined end point of renal failure. Both urinary L-FABP and H-FABP predicted renal outcome, with the calculated sensitivity and specificity of 81 and 83% for both.

Conclusions. Urinary L-FABP and urinary H-FABP are increased in patients with iMN. There was a high correlation between L-FABP and H-FABP, suggesting the concurrent development or existence of proximal and distal tubular cell injury. Both L-FABP and H-FABP predicted prognosis in patients with iMN. These markers may be of interest as research tools; however, they are not superior to more conventional marker proteins.

Methods. We recruited a cohort of 104 biopsy-diagnosed MN patients and 142 healthy subjects that served as controls. Genotyping of PAI-1 gene polymorphisms was performed using allele-specific polymerase chain reaction methods. We then analysed associations between PAI-1 gene 4G/5G polymorphisms and clinical manifestations and progression of MN.

Results. The genotype distribution had no effect on the development of MN. The last measured creatinine clearance in MN patients having the 4G/4G genotype was significantly lower than in patients having the 4G/5G or 5G/5G genotypes (43.6 ± 33.6, 55.8 ± 44.3 and 73.3 ± 29.8 ml/min, respectively, P = 0.008). Coronary artery diseases were more prevalent in patients having the 4G5G (14/32%) and 4G4G genotypes (4/11%) than in those having the 5G5G genotype (1/5%, P = 0.008). Peripheral vascular events were more prevalent in patients having the 4G5G (18/41%) and 4G4G (6/16%) genotypes than in those having the 5G5G genotype (3/14%, P = 0.021). Disease progression occurred more frequently in patients having the 4G4G (20/53%) and 4G5G (25/57%) genotypes compared with those having the 5G5G genotype (5/23%, P = 0.026).

Conclusions. The presence of the 4G allele was associated with renal deterioration and increased cardiovascular as well as other vascular events in MN patients. These findings should prompt specific considerations for the treatment of MN in patients having the 4G4G genotype.

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. We used the variance components decomposition approach (implemented in the software package SOLAR) to perform linkage analysis on 848 participants from 26 families. A total of 417 microsatellite markers were genotyped at an average interval of 10 cM spanning 22 autosomal chromosomes.

Results. All phenotypes were measured by standard procedures. Mean ± SD values of ACR, SrCr, CrCl and eGFR were 0.06 ± 0.38, 0.85 ± 0.72 mg/dl, 129.85 ± 50.37 ml/min and 99.18 ± 25.69 ml/min/1.73 m² body surface area, respectively. All four CKD phenotypes exhibited significant heritabilities (P < 0.0001). A genome-wide scan showed linkage on chromosome 2p25 for SrCr, CrCl and eGFR. Significant linkage was also detected on chromosome 9q21 for eGFR [logarithm of the odds (LOD) score = 3.87, P = 0.00005] and SrCr (LOD score = 2.6, P = 0.00026). ACR revealed suggestive evidence for linkage to a region on chromosome 20q12 (LOD score = 2.93, P = 0.00020).

Conclusion. Findings indicate that chromosomal regions 2p25, 9q21 and 20q12 may have functional relevance to CKD phenotypes in Mexican Americans.

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. 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. 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. We report on three cases, where renal biopsy in pediatric and adolescent patients led to various but clinically significant complications. In each patient two cores of renal parenchyma from the upper pole of the renal transplant or the lower pole of the right native kidney, respectively, were obtained with two attempts.

Results. Immediate post-bioptic ultrasound did not show any abnormalities. Setting of an AVF was suspected when complications occurred and ultrasound and Doppler studies showed AVF. The diagnosis was confirmed by angiography and occlusion of the fistulae was performed in the same session.

Conclusion. We conclude that persistent AVF is an uncommon but serious complication after renal biopsy. Well-timed angiography when AVF is suspected can prevent loss of function, especially in transplant recipients.

Methods. VA data were collected for each patient at study entry (1996–2007). Practice pattern data from the facility medical director, nurse manager and VA surgeon were also analysed.

Results. Since 2005, a native arteriovenous fistula (AVF) was used by 67–91% of prevalent patients in Japan, Italy, Germany, France, Spain, the UK, Australia and New Zealand, and 50–59% in Belgium, Sweden and Canada. From 1996 to 2007, AVF use rose from 24% to 47% in the USA but declined in Italy, Germany and Spain. Moreover, graft use fell by 50% in the USA from 58% use in 1996 to 28% by 2007. Across three phases of data collection, patients consistently were less likely to use an AVF versus other VA types if female, of older age, having greater body mass index, diabetes, peripheral vascular disease or recurrent cellulitis/gangrene. In addition, countries with a greater prevalence of diabetes in HD patients had a significantly lower percentage of patients using an AVF. Despite poorer outcomes for central vein catheters, catheter use rose 1.5- to 3-fold among prevalent patients in many countries from 1996 to 2007, even among non-diabetic patients 18–70 years old. Furthermore, 58–73% of patients new to end-stage renal disease (ESRD) used a catheter for the initiation of HD in five countries despite 60–79% of patients having been seen by a nephrologist >4 months prior to ESRD. Patients were significantly (P < 0.05) less likely to start dialysis with a permanent VA if treated in a faciity that (1) had a longer time from referral to access surgery evaluation or from evaluation to access creation and (2) had longer time from access creation until first AVF cannulation. The median time from referral until access creation varied from 5–6 days in Italy, Japan and Germany to 40–43 days in the UK and Canada. Compared to patients using an AVF, patients with a catheter displayed significantly lower mean Kt/V levels.

Conclusions. Most countries meet the contemporary National Kidney Foundation's Kidney Disease Outcomes Quality Initiative goal for AVF use; however, there is still a wide variation in VA preference. Delays between the creation and cannulation must be improved to enhance the chances of a future permanent VA. Native arteriovenous fistula is the VA of choice ensuring dialysis adequacy and better patient outcomes. Graft is, however, a better alternative than catheter for patients where the creation of an attempted AVF failed or could not be created for different reasons.

Methods. Relative risks (RRs) from a multivariable Cox mortality model, based on observational haemodialysis (HD) patient data from DOPPS I (1996–2001, seven countries), were used. The four practices were the percent of patients with Kt/V ≥1.2, haemoglobin ≥11 g/dl (110 g/l), albumin ≥4.0 g/dl (40g/l) and catheter use, and were significantly related to mortality when modelled together. DOPPS II data (2002–2004, 12 countries) were used to evaluate the relationship between PRS and mortality risk using Cox regression.

Results. For facilities in DOPPS I and II, changes in PRS over time were significantly correlated with changes in the standardized mortality ratio (SMR). The PRS ranged from 1.0 to 2.1. Overall, the adjusted RR of death was 1.05 per 0.1 points higher PRS (P < 0.0001). For facilities in both DOPPS I and II (N = 119), a 0.2 decrease in PRS was associated with a 0.19 decrease in SMR (P = 0.005). On average, facilities that improved PRS practices showed significantly reduced mortality over the same time frame.

Conclusions. The PRS assesses modifiable HD practices that are linked to improved patient survival. Further refinements might lead to improvements in the PRS and will address regional variations in the PRS/mortality relationship.

Methods. We present mock-dialysis experiments using magnetically assisted HD (MAHD) that we very recently introduced for the selective removal of target toxins. MAHD is based on the preparation of conjugates (Cs) made up of biocompatible ferromagnetic nanoparticles (FNs) and a specifically designed targeted binding substance that must have a high affinity for a specific target toxin substance. The FN–targeted binding substance Cs should be administered to the patient prior to MAHD to allow for binding with the target toxin substance in the bloodstream. The complex FN–targeted binding substance–target toxin substance will then be removed by a ‘magnetic dialyzer’ that is installed in the dialysis machine in series to the conventional dialyzer. In the present work, we compared the in vitro efficiency of MAHD to conventional HD for the removal of homocysteine (Hcy) during mock-dialysis experiments.

Results. These mock-dialysis experiments performed on Hcy revealed that both the removal rate and the overall removal efficiency of MAHD were significantly greater than conventional HD.

Conclusions. MAHD appears to be a promising method that can be employed for the selective and more efficient extraction of toxins that are not adequately removed by conventional HD.

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.

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. 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. 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. 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. Four haemodialysis patients with severe Gd-related nephrogenic systemic fibrosis were treated with intravenous sodium thiosulfate for 3–5 months. Symptoms and patients’ experiences were investigated. The dialysate Gd content was monitored.

Results. We observed no major clinical improvements in any patient. In one patient, we found slightly improved joint motion. Two patients had a subjective impression of slight improvements of joint motion and skin abnormalities. The dialysate Gd content was raised by the treatment, up to fivefold.

Conclusions. We could not confirm that sodium thiosulfate treatment results in marked and rapid improvement in late stages of Gd-related nephrogenic systemic fibrosis. However, dialysate contents of Gd seemed to increase. It is unknown whether increased Gd excretion will lead to long-term clinical improvements in late stages of nephrogenic systemic fibrosis.

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.

Objective. The purpose of this study was to evaluate the results of a dialysis policy dedicated to unplanned dialysis patients. The aim of this policy was to increase the use of peritoneal dialysis (PD) in an attempt to reduce the need for tunnelled catheter.

Methods. One hundred seventy-one patients from a single centre, who started dialysis between 1 January 2004 and 31 December 2006, were prospectively followed until 31 December 2006. Unplanned dialysis patients were defined as patients entering in dialysis with no vascular access or peritoneal dialysis catheter. PD was presented as a modality of choice for renal replacement therapy to avoid the need for a tunnelled HD catheter.

Results. There were 60 unplanned dialysis patients during the study period. Among these patients, 34 agreed to be treated by PD. Compared with unplanned peritoneal dialysis patients, unplanned haemodialysis patients had a greater modified Charlson's comorbidity index (5.9 ± 2.4 versus 4.4 ± 1.9, P < 0.05). The mean duration of the temporary catheter period was 32 ± 29 days (median: 24 days) for haemodialysis patients compared with 26 ± 21 days (median: 25 days) for peritoneal dialysis patients (P = NS). The initial hospitalization duration was similar in haemodialysis patients and peritoneal dialysis patients (24 ± 28 versus 30 ± 33 days; median value: 17 versus 20 days, P = NS). PD was started 8.6 ± 10 days (median: 4 days) after catheter insertion. A tunnelled catheter was used only in three patients until peritoneal dialysis was initiated. Acute automated peritoneal dialysis was used in 19 patients. Among 26 haemodialysis patients, 23 were dialyzed through a tunnelled catheter. Of these 23 patients, 15 were successfully converted to fistula. Median time for fistula creation was 2.6 months after dialysis initiation; median time for fistula utilization was 4.4 months. Actuarial patients survival at 1 year was 79% on haemodialysis compared with 83% on peritoneal dialysis (P = NS). After adjustment of the initial modified Charlson's comorbidity index, dialysis modality had no impact on patient's survival. There was no significant difference between haemodialysis patients and peritoneal dialysis patients regarding survival free of re-hospitalization. Actuarial survival free of peritonitis was 73% at 6 months and 58% at 1 year.

Conclusion. Peritoneal dialysis is a safe and efficient alternative to haemodialysis for unplanned dialysis patients. Peritoneal dialysis offers the advantage of reducing the need for tunnelled catheter in unplanned dialysis patients.

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.

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. Human mesothelial cells were cultured from the effluents of stable dialysis patients. Apoptosis was quantified in cultured mesothelial cells and in peritoneal effluents. Confocal microscopy and inhibitors were used to assess molecular mechanisms.

Results. Peritoneal dialysis solutions with a high content of both glucose and glucose degradation products, but not those with low glucose degradation product content, induced mesothelial cell apoptosis and loss of cell viability in culture and in vivo. 3,4-DGE also induced mesothelial cell apoptosis. Apoptosis induced by peritoneal dialysis solutions and 3,4-DGE was associated with oligomerization of Bax at mitochondria and caspase activation. Bax antagonism prevented caspase activation, apoptosis and cell death. The pancaspase inhibitor zVAD was also protective.

Conclusion. 3,4-DGE and peritoneal dialysis solutions with a high content in glucose degradation products induce mesothelial cell apoptosis by a Bax-dependent mechanism. This could contribute to chronic demesothelization in peritoneal dialysis.

Methods. Transplant professionals attending the 2006 World Transplant Congress responded to a survey assessing their process of informed consent, evaluation and communication of living donor risk. US-based respondents were compared to non-US respondents.

Results. There were 221 respondents from 177 transplant centers and 40 countries (48% US respondents). Across US and non-US transplant centers, potential donors were most likely to receive written material about living donor risk by mail prior to evaluation, receive risk information in person during evaluation, have a psychosocial evaluation, which usually lasted longer than 30 min and sign an official donation consent form presented to them by a surgeon or nephrologist. Although over 75% of respondents stated that donors received information about medical risks such as hypertension, chronic kidney disease and potential need for dialysis, there was less consistency regarding whether or not respondents conveyed an increased risk of these medical complications to donors. Additionally, the financial and psychosocial costs associated with being a living donor were inconsistently communicated to donors during the informed consent process. Compared to non-US respondents, US respondents were more likely to use written material and visual aids to convey risks to donors, have mandatory psychosocial evaluations and provide access to donor support groups. US transplant centers were also more likely to discuss the possibility of the donors needing dialysis or a transplant if their remaining kidney fails in the future, possible travel expenses and loss of work income due to donation recovery. Conversely, the US respondents were less likely to offer long-term follow-up and to utilize nephrologists to obtain written donor consent for donation.

Conclusions. As dependence on living organ donation increases best practices for informed consent, donor evaluation and uniform risk conveyance need to be established. This may be accomplished by using a model informed consent template to ensure that informed consent from donors is consistently obtained.

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.

Methods. We monitored BKV load on serum and urine samples by Real-Time TaqMan PCR in 229 renal transplant recipients in the first year post-transplantation. Overall, 2025 serum and 2025 urine samples were evaluated. A graft biopsy was performed in 47/229 patients to investigate the declining renal function. Operating characteristics [sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV)] and receiver operating characteristic (ROC) curve analysis at different viral load values were calculated.

Results. Serum BKV viral load was >10⁴ in 5/229 patients (2.2%). A histological diagnosis of BKVAN was made in 3/229 patients (1.3%): 3/5 (60.0%) among those with serum viral load >10⁴ and 3/4 (75.0%) in those with >1.6 x 10⁴. Operating characteristics of a serum BK load of 10⁴ for the diagnosis of BKVAN were as follows: sensitivity, 100%; specificity, 99.1%; NPV, 100%; PPV, 59.4%. Specificity and PPV rose to 99.6% and 75.0% when using a cut-off level of 1.6 x 10⁴ copies/mL.

Conclusions. The recommended level of BK viraemia of 10⁴ copies/mL is useful to identify patients at risk of BKVAN, although specificity and PPV increase by using a cut-off level of 1.6 x 10⁴ copies/mL. BK replication may occur in the first 3 months post-transplantation and subsequently recede. Therefore, the temporal profile of BKV replication has to be accurately evaluated and occasionally elevated values should prompt a closer monitoring.

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 i