Effects of Allopurinol on the Progression of Chronic Kidney Disease.

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).

Assessment of current practice and barriers to antimicrobial prophylaxis in peritoneal dialysis patients.

BACKGROUND: Existing Australasian and international guidelines outline antibiotic and antifungal measures to prevent the development of treatment-related infection in peritoneal dialysis (PD) patients. Practice patterns and rates of PD-related infection vary widely across renal units in Australia and New Zealand and are known to vary significantly from guideline recommendations, resulting in PD technique survival rates that are lower than those achieved in many other countries. The aim of this study was to determine if there is an association between current practice and PD-related infection outcomes and to identify the barriers and enablers to good clinical practice. METHODS: This is a multicentre network study involving eight PD units in Australia and New Zealand, with a focus on adherence to guideline recommendations on antimicrobial prophylaxis in PD patients. Current practice was established by asking the PD unit heads to respond to a short survey about practice/protocols/policies and a 'process map' was constructed following a face-to-face interview with the primary PD nurse at each unit. The perceived barriers/enablers to adherence to the relevant guideline recommendations were obtained from the completion of 'cause and effect' diagrams by the nephrologist and PD nurse at each unit. Data on PD-related infections were obtained for the period 1 January 2011 to 31 December 2011. RESULTS: Perceived barriers that may result in reduced adherence to guideline recommendations included lack of knowledge, procedural lapses, lack of a centralized patient database, patients with non-English speaking background, professional concern about antibiotic resistance, medication cost and the inability of nephrologists and infectious diseases staff to reach consensus on unit protocols. The definitions of PD-related infections used by some units varied from those recommended by the International Society for Peritoneal Dialysis, particularly with exit-site infection (ESI). Wide variations were observed in the rates of ESI (0.06-0.53 episodes per patient-year) and peritonitis (0.31-0.86 episodes per patient-year). CONCLUSIONS: Despite the existence of strongly evidence-based guideline recommendations, there was wide variation in adherence to these recommendations between PD units which might contribute to PD-related infection rates, which varied widely between units. Although individual patient characteristics may account for some of this variability, inconsistencies in the processes of care to prevent infection in PD patients also play a role.

End-Stage Kidney Disease Due to Fibrillary Glomerulonephritis and Immunotactoid Glomerulopathy - Outcomes in 66 Consecutive ANZDATA Registry Cases.

BACKGROUND: Fibrillary glomerulonephritis (FGN) and immunotactoid glomerulopathy (IG) are uncommon and characterised by non-amyloid fibrillary glomerular deposits. The aim of this study was to investigate characteristics and outcomes of patients undergoing renal replacement therapy (RRT) for end-stage kidney disease (ESKD) secondary to FGN and IG. METHODS: All ESKD patients who commenced RRT in Australia and New Zealand 1 January 1990 to 31 December 2010 were included. Outcomes were assessed by Kaplan-Meier, multivariate logistic-regression analysis and multivariable Cox proportional-hazards survival analysis. RESULTS: Of 45,216 individuals with ESKD, 55 (0.12%) had FGN and 11 (0.02%) had IG. The median survival of FGN patients on dialysis (5.63 years, 95% CI 3.31-7.96) was not significantly different from patients with other ESKD causes (median 4.01 years, 95% CI 4.34-4.47; log-rank 1.32, p = 0.25), but was significantly longer than that of IG patients (median 2.93 years, 95% CI 0.00-6.17; log-rank 4.8, p = 0.03). Thirteen (24%) FGN patients received 13 renal-allografts, 4 (36%) IG patients received 4 renal-allografts and 11,528 (26%) other ESKD patients received 12,278 renal-allografts. FGN patients experienced comparable outcomes to other ESKD patients for both 10-year patient survival (100 vs. 84%, p = 0.93) and renal-allograft survival (67 vs. 76%, p = 0.06). For IG, the median follow-up was 3.66 years with 75% patient survival and 100% renal-allograft survival. One (8%) FGN patient and 1 (25%) IG patient experienced recurrent FGN and IG respectively in their allograft. CONCLUSION: Patients with FGN have comparable dialysis and renal transplant outcomes to patients with other causes of ESKD. IG patients have inferior survival on dialysis, although renal transplant outcomes are acceptable. Disease recurrence in renal-allografts was low for both FGN and IG.

Peritoneal dialysis outcomes after temporary haemodialysis transfer for peritonitis.

BACKGROUND: There has not been a comprehensive examination to date of peritoneal dialysis (PD) outcomes after temporary haemodialysis (HD) transfer for peritonitis. METHODS: The study included all incident Australian patients who experienced peritonitis between 1 October 2003, and 31 December 2011, using Australia and New Zealand Dialysis and Transplant Registry data. Patients were grouped into three categories: Interim HD, Permanent HD and Never HD based on HD transfer status after the first peritonitis. The independent predictors of HD transfer and subsequent return to PD were determined by multivariable, multilevel mixed-effects logistic regression analysis. Matched case-control analyses were performed to compare clinical outcomes (e.g. patient survival) between groups. RESULTS: Of the 3305 patients who experienced peritonitis during the study period, 553 episodes (16.7%) resulted in transfer to HD and 101 patients subsequently returned to PD. HD transfer was significantly and independently predicted by inpatient treatment of peritonitis [odds ratio (OR) 11.45, 95% confidence interval (CI) 7.14-18.36] and the recovered microbiologic profile of organisms recognized to be associated with moderate (20-40%) to high (>40%) rates of catheter removal (moderate: OR 2.45, 95% CI 1.89-3.17; high: OR 8.63, 95% CI 6.44-11.57). Matched case-control analyses yielded comparable results among Interim, Permanent and Never HD groups in terms of patient survival (P = 0.28), death-censored technique survival [hazard ratio (HR) 0.87, 95% CI 0.59-1.28; P = 0.48] and peritonitis-free survival (HR 0.84, 95% CI 0.50-1.39, P = 0.49). CONCLUSIONS: In an observational registry study of first peritonitis episodes, temporary HD transfer was not associated with inferior patient-level clinical outcomes when compared with others who either never required HD transfer or remained on HD permanently if all patient-level and peritonitis-related factors were considered equal. Therefore, return to PD after a temporary HD due to peritonitis should not be discouraged in appropriate PD patients.

End-stage kidney disease due to Alport syndrome: outcomes in 296 consecutive Australia and New Zealand Dialysis and Transplant Registry cases.

BACKGROUND: Alport syndrome is a rare inheritable renal disease. Clinical outcomes for patients progressing to end-stage kidney disease (ESKD) are not well described. METHODS: This study aimed to investigate the characteristics and clinical outcomes of patients from Australia and New Zealand commencing renal replacement therapy (RRT) for ESKD due to Alport syndrome between 1965 and 1995 (early cohort) and between 1996 and 2010 (contemporary cohort) compared with propensity score-matched, RRT-treated, non-Alport ESKD controls. RESULTS: A total of 58 422 patients started RRT during this period of which 296 (0.5%) patients had Alport ESKD. In the early cohort, Alport ESKD was associated with superior dialysis patient survival [adjusted hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.20-0.83, P = 0.01], renal allograft survival (HR: 0.74, 95% CI: 0.54-1.01, P = 0.05) and renal transplant patient survival (HR: 0.43, 95% CI: 0.28-0.66, P < 0.001) compared with controls. In the contemporary cohort, no differences were observed between the two groups for dialysis patient survival (HR: 1.42, 95% CI: 0.65-3.11, P = 0.38), renal allograft survival (HR: 1.01, 95% CI: 0.57-1.79, P = 0.98) or renal transplant patient survival (HR: 0.67, 95% CI: 0.26-1.73, P = 0.41). One Alport patient (0.4%) had post-transplant anti-glomerular basement membrane (anti-GBM) disease. Four female and 41 male Alport patients became parents on RRT with generally good neonatal outcomes. CONCLUSION: Alport syndrome patients experienced comparable dialysis and renal transplant outcomes to matched non-Alport ESKD controls in the contemporary cohort due to relatively greater improvements in outcomes for non-Alport ESKD patients over time. Post-transplant anti-GBM disease was rare.

Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis.

BACKGROUND: Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes. METHODS: Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis. RESULTS: Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events. CONCLUSIONS: Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.

Anti-glomerular basement membrane antibody disease is an uncommon cause of end-stage renal disease.

There are few reports regarding outcomes of anti-glomerular basement membrane (GBM) disease in patients who underwent renal replacement therapy. To help define this we studied all patients with anti-GBM disease who started renal replacement therapy for end-stage renal disease (ESRD) in Australia and New Zealand (ANZDATA Registry) between 1963 and 2010 encompassing 449 individuals (0.8 percent of all ESRD patients). The median survival on dialysis was 5.93 years with death predicted by older age and a history of pulmonary hemorrhage. Thirteen patients recovered renal function, although 10 subsequently experienced renal death after a median period of 1.05 years. Of the 224 patients who received their first renal allograft, the 10-year median patient and renal allograft survival rates were 86% and 63%, respectively. Six patients experienced anti-GBM disease recurrence in their allograft, which led to graft failure in two. Using multivariable Cox regression analysis, patients with anti-GBM disease had comparable survival on dialysis or following renal transplantation (hazard ratios of 0.86 and 1.03, respectively) compared to those with ESRD due to other causes. Also, renal allograft survival (hazard ratio of 1.03) was not altered compared to other diseases requiring a renal transplant. Thus, anti-GBM disease was an uncommon cause of ESRD, and not associated with altered risks of dialysis, transplant or first renal allograft survival. Death on dialysis was predicted by older age and a history of pulmonary hemorrhage.

Daily variation in death in patients treated by long-term dialysis: comparison of in-center hemodialysis to peritoneal and home hemodialysis.

BACKGROUND: There has been little study to date of daily variation in cardiac death in dialysis patients and whether such variation differs according to dialysis modality and session frequency. STUDY DESIGN: Observational cohort study using ANZDATA (Australia and New Zealand Dialysis and Transplant) Registry data. SETTING & PARTICIPANTS: All adult patients with end-stage kidney failure treated by dialysis in Australia and New Zealand who died between 1999 and 2008. PREDICTORS: Timing of death (day of week), dialysis modality, hemodialysis (HD) session frequency, and demographic, clinical, and facility variables. OUTCOMES & MEASUREMENTS: Cardiac and noncardiac mortality. RESULTS: 14,636 adult dialysis patients died during the study period (HD, n = 10,338; peritoneal dialysis [PD], n = 4,298). Cardiac death accounted for 40% of deaths and was significantly more likely to occur on Mondays in in-center HD patients receiving 3 or fewer dialysis sessions per week (n = 9,503; adjusted OR, 1.26; 95% CI, 1.14-1.40; P < 0.001 compared with the mean odds of cardiac death for all days of the week). This daily variation in cardiac death was not seen in PD patients, in-center HD patients receiving more than 3 sessions per week (n = 251), or home HD patients (n = 573). Subgroup analyses showed that deaths related to hyperkalemia and myocardial infarction also were associated with daily variation in risk in HD patients. This pattern was not seen for vascular, infective, malignant, dialysis therapy withdrawal, or other deaths. LIMITATIONS: Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Possible type 2 statistical error due to limited sample size of home HD and enhanced-frequency HD cohorts. CONCLUSIONS: Daily variation in the pattern of cardiac deaths was observed in HD patients receiving 3 or fewer dialysis sessions per week, but not in PD, home HD, and HD patients receiving more than 3 sessions per week.

End-stage renal failure due to amyloidosis: outcomes in 490 ANZDATA registry cases.

BACKGROUND: There are few reports regarding the long-term renal replacement therapy (RRT) outcomes of amyloidosis. METHODS: In this retrospective, multi-centre, multi-country registry analysis, all patients with and without amyloidosis who commenced RRT for end-stage renal failure (ESRF) in Australia and New Zealand between 1963 and 2010 were included. RESULTS: Of 58 422 patients who underwent RRT during the study period, 490 (0.8%) had ESRF secondary to amyloidosis. The median survival of amyloidosis patients on dialysis (2.09 years, 95% CI 1.85-2.32 years) was significantly inferior to that of patients with other causes of ESRF (4.45 years, 95% CI 4.39-4.51 years) (log-rank score 242, P < 0.001). The survival of amyloidosis patients receiving peritoneal dialysis (1.9 years, 95% CI 1.58-2.22) was comparable with those receiving haemodialysis (2.17 years, 95% CI 1.89-2.45) (P = 0.18). Fifty-three (13.8%) amyloidosis patients died of amyloidosis complications. Forty-six patients underwent renal transplantation with first graft survival rates of 45% at 5 years and 26% at 10 years. Nine (16.4%) patients experienced amyloidosis recurrence in their allografts, which led to graft failure in six patients. ESRF patients with amyloidosis experienced inferior median first renal allograft survival (4.55 years, 95% CI 1.96-7.15 versus 10.7 years, 95% CI 10.5-11.0, P = 0.001) and transplant patient survival (6.03 years, 95% CI 2.71-9.36 versus 16.8 years, 95% CI 16.4-17.1, P < 0.001) compared with patients with other causes of ESRF. Respective 10-year patient survival rates were 37 and 69%. CONCLUSIONS: Amyloidosis was associated with poor patient survival following dialysis and/or renal transplantation, poor renal allograft survival and a significant incidence of disease recurrence in the allograft. An appreciable proportion of amyloid ESRF patients died of amyloidosis-related complications.

Effects of biocompatible versus standard fluid on peritoneal dialysis outcomes.

The clinical benefits of using "biocompatible" neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: -0.22 and -0.28 ml/min per 1.73 m(2) per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, -0.09 and -0.10 ml/min per 1.73 m(2) per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis.

Recent peritonitis associates with mortality among patients treated with peritoneal dialysis.

Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥ 2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4-8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days.

Mycophenolate and lower graft function reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination.

In late 2009 transplant organizations recommended that kidney recipients be vaccinated for pandemic H1N1 influenza (pH1N1); however, the vaccine efficacy was unknown. We had offered a monovalent non-adjuvanted pH1N1 vaccine to transplant recipients. Here we compared the pre- and post-vaccination seroresponses of 151 transplant recipients to that of 71 hemodialysis patients and 30 healthy controls. Baseline seroprotection was similar between groups but was significantly different at 1 month (44, 56, and 87%, respectively). Seroconversion was significantly less common for transplant recipients (32%) than dialysis patients (45%) and healthy controls (77%). After adjusting for age and gender, dialysis patients were significantly more likely (2.7-fold) to achieve new seroprotection than transplant recipients. The likelihood of seroprotection in transplant recipients was significantly reduced by mycophenolate use (adjusted odds ratio 0.24), in a dose-dependent manner, and by reduced eGFR (adjusted odds ratio 0.16 for worst to best). Seroprotection and geometric mean antibody titers increased substantially in 49 transplant recipients who subsequently received the 2010 seasonal influenza vaccine. Thus, patients requiring renal replacement therapy had reduced seroresponses to vaccination with the monovalent vaccine compared with healthy controls. Transplant recipient responses were further reduced if they were receiving mycophenolate or had significantly lower graft function.

Repeated peritoneal dialysis-associated peritonitis: a multicenter registry study.

BACKGROUND: Determinants and outcomes of peritoneal dialysis (PD)-associated peritonitis occurring within 4 weeks of completion of therapy of a prior episode caused by the same (relapse) or different organism (recurrence) recently have been characterized. However, determinants and outcomes of peritonitis occurring more than 4 weeks after treatment of a prior episode caused by the same (repeated) or different organism (nonrepeated) are poorly understood. STUDY DESIGN: Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. SETTING & PARTICIPANTS: All Australian PD patients between October 1, 2003, and December 31, 2007, with first episodes of repeated or nonrepeated peritonitis. PREDICTORS: Repeated versus nonrepeated peritonitis, according to International Society of PD (ISPD) criteria. OUTCOMES & MEASUREMENTS: Relapse, hospitalization, catheter removal, hemodialysis transfer, and death. RESULTS: After a peritonitis episode, the probability that a subsequent episode represented repeated rather than nonrepeated peritonitis was highest in the second month (41%), then progressively decreased to a stable level of 14% from 6 months onward. When first episodes of repeated (n = 245) or nonrepeated peritonitis (n = 824) were analyzed, repeated peritonitis was predicted independently by a shorter elapsed time from the prior episode (adjusted OR per day elapsed, 0.91; 95% CI, 0.88-0.94). Staphylococcus aureus and coagulase-negative staphylococcus were isolated more frequently in repeated peritonitis, whereas Gram-negative, streptococcal, and fungal organisms were recovered more frequently in nonrepeated peritonitis. Using multivariate logistic regression, repeated peritonitis was associated independently with higher relapse (OR, 5.41; 95% CI, 3.72-7.89) and lower hospitalization rates (OR, 0.63; 95% CI, 0.46-0.85), but catheter removal, hemodialysis transfer, and death rates similar to nonrepeated peritonitis. LIMITATIONS: Limited covariate adjustment. Residual confounding and coding bias could not be excluded. CONCLUSIONS: Repeated and nonrepeated peritonitis episodes are caused by different spectra of micro-organisms and have different outcomes. Study findings suggest that the ISPD definition for repeated peritonitis should be limited to 6 months.

Seasonal variation in peritoneal dialysis-associated peritonitis: a multi-centre registry study.

BACKGROUND: The role of seasonal variation in peritoneal dialysis (PD)-related peritonitis has been limited to a few small single-centre studies. METHODS: Using all 6610 Australian patients receiving PD between 1 October 2003 and 31 December 2008, we evaluated the influence of seasons on peritonitis rates (Poisson regression) and outcomes (multivariable logistic regression). RESULTS: The overall rate of peritonitis was 0.59 episodes per patient-year of treatment. Using winter as the reference season, the peritonitis incidence rate ratios (95% confidence interval) for summer, autumn and spring were 1.02 (0.95-1.09), 1.01 (0.94-1.08) and 0.99 (0.92-1.06), respectively. Significant seasonal variations were observed in the rates of peritonitis caused by coagulase-negative Staphylococci (spring and summer peaks), corynebacteria (winter peak) and Gram-negative organisms (summer and autumn peaks). There were trends to seasonal variations in fungal peritonitis (summer and autumn peaks) and pseudomonas peritonitis (summer peak). No significant seasonal variations were observed for other organisms. Peritonitis outcomes did not significantly vary according to season. CONCLUSIONS: Seasonal variation has no appreciable influence on overall PD peritonitis rates or clinical outcomes. Nevertheless, significant seasonal variations were observed in the rates of peritonitis due to specific microorganisms, which may allow institutions to more precisely target infection control strategies prior to higher risk seasons.

Use of aminoglycosides for peritoneal dialysis-associated peritonitis does not affect residual renal function.

BACKGROUND: Aminoglycosides offer several potential benefits in their treatment of peritoneal dialysis (PD)-associated peritonitis, including low cost, activity against Gram-negative organisms (including Pseudomonas aeruginosa), synergistic bactericidal activity against some Gram-positive organisms (such as Staphylococci) and relatively low propensity to promote antimicrobial resistance. However, there is limited conflicting evidence that aminoglycosides may accelerate loss of residual renal function (RRF) in PD patients. The aim of this study was to study the effect of aminoglycoside use on slope of decline in RRF. METHODS: The study included 2715 Australian patients receiving PD between October 2003 and December 2007 in whom at least two measurements of renal creatinine clearance were available. Patients were divided according to tertiles of slope of RRF decline (rapid, intermediate and slow). The primary outcome was the slope of RRF over time in patients who received aminoglycosides for PD peritonitis versus those who did not. RESULTS: A total of 1412 patients (52%) experienced at least one episode of PD peritonitis. An aminoglycoside was used as the initial empiric antibiotic in 1075 patients. The slopes of RRF decline were similar in patients treated and not treated with at least one course of aminoglycoside (median [interquartile range] -0.26 [-1.17 to 0.04] mL/min/1.73 m(2)/month versus -0.22 [-1.11 to 0.01] mL/min/1.73 m(2)/month, P = 0.9). The slopes of RRF decline were also similar in patients receiving repeated courses of aminoglycoside. CONCLUSIONS: Empiric treatment with aminoglycoside for peritonitis was not associated with an adverse effect on RRF in PD patients.

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial.

BACKGROUND: The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. METHODS: Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. RESULTS: Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference -0.004 per month, 95% confidence interval (95% CI) -0.005 to -0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9-39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. CONCLUSIONS: Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted.

End-stage kidney disease due to haemolytic uraemic syndrome--outcomes in 241 consecutive ANZDATA registry cases.

BACKGROUND: The aim of this study was to investigate the characteristics and outcomes of patients receiving renal replacement therapy for end-stage kidney disease (ESKD) secondary to haemolytic uraemic syndrome (HUS). METHODS: The study included all patients with ESKD who commenced renal replacement therapy in Australia and New Zealand between 15/5/1963 and 31/12/2010, using data from the ANZDATA Registry. HUS ESKD patients were compared with matched controls with an alternative primary renal disease using propensity scores based on age, gender and treatment era. RESULTS: Of the 58422 patients included in the study, 241 (0.4%) had ESKD secondary to HUS. HUS ESKD was independently associated with younger age, female gender and European race. Compared with matched controls, HUS ESKD was not associated with mortality on renal replacement therapy (adjusted hazard ratio [HR] 1.14, 95% CI 0.87-1.50, p = 0.34) or dialysis (HR 1.34, 95% CI 0.93-1.93, p = 0.12), but did independently predict recovery of renal function (HR 54.01, 95% CI 1.45-11.1, p = 0.008). 130 (54%) HUS patients received 166 renal allografts. Overall renal allograft survival rates were significantly lower for patients with HUS ESKD at 1 year (73% vs 91%), 5 years (62% vs 85%) and 10 years (49% vs 73%). HUS ESKD was an independent predictor of renal allograft failure (HR 2.59, 95% CI 1.70-3.95, p < 0.001). Sixteen (12%) HUS patients experienced failure of 22 renal allografts due to recurrent HUS. HUS ESKD was not independently associated with the risk of death following renal transplantation (HR 0.92, 95% CI 0.35-2.44, p = 0.87). CONCLUSIONS: HUS is an uncommon cause of ESKD, which is associated with comparable patient survival on dialysis, an increased probability of renal function recovery, comparable patient survival post-renal transplant and a heightened risk of renal transplant graft failure compared with matched ESKD controls.

The effects of living distantly from peritoneal dialysis units on peritonitis risk, microbiology, treatment and outcomes: a multi-centre registry study.

BACKGROUND: The aim of the study was to determine whether distance between residence and peritoneal dialysis (PD) unit influenced peritonitis occurrence, microbiology, treatment and outcomes. METHODS: The study included all patients receiving PD between 1/10/2003 and 31/12/2008, using ANZDATA Registry data. RESULTS: 365 (6%) patients lived ≥100 km from their nearest PD unit (distant group), while 6183 (94%) lived <100 km (local group). Median time to first peritonitis in distant patients (1.34 years, 95% CI 1.07-1.61) was significantly shorter than in local patients (1.68 years, 95% CI 1.59-1.77, p = 0.001), whilst overall peritonitis rates were higher in distant patients (incidence rate ratio 1.32, 95% CI 1.20-1.46). Living ≥100 km away from a PD unit was independently associated with a higher risk of S. aureus peritonitis (adjusted odds ratio [OR] 1.64, 95% CI 1.09-2.47). Distant patients with first peritonitis episodes were less likely to be hospitalised (64% vs 73%, p = 0.008) and receive antifungal prophylaxis (4% vs 10%, p = 0.01), but more likely to receive vancomycin-based antibiotic regimens (52% vs 42%, p < 0.001). Using multivariable logistic regression analysis of peritonitis outcomes, distant patients were more likely to be cured with antibiotics alone (OR 1.55, 95% CI 1.03-2.24). All other outcomes were comparable between the two groups. CONCLUSIONS: Living ≥100 km away from a PD unit was associated with increased risk of S. aureus peritonitis, modified approaches to peritonitis treatment and peritonitis outcomes that were comparable to, or better than patients living closer to a PD unit. Staphylococcal decolonisation should receive particular consideration in remote living patients.

Relapsing and recurrent peritoneal dialysis-associated peritonitis: a multicenter registry study.

BACKGROUND: The causes, predictors, treatment, and outcomes of relapsed and recurrent peritoneal dialysis (PD)-associated peritonitis are poorly understood. STUDY DESIGN: Observational cohort study using Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry data. SETTING & PARTICIPANTS: All Australian PD patients between October 1, 2003, and December 31, 2007, with first episodes of peritonitis. PREDICTORS: Demographic, clinical, and facility variables and type of peritonitis; relapse (same organism or culture-negative episode occurring within 4 weeks of completion of therapy of a prior episode or 5 weeks if vancomycin used); recurrence (different organism occurring within 4 weeks of completion of therapy of a prior episode or 5 weeks if vancomycin used); control (first peritonitis episode without relapse or recurrence). OUTCOMES & MEASUREMENTS: Hospitalization, catheter removal, hemodialysis therapy transfer, death. RESULTS: Of 6,024 PD patients studied, first episodes of relapsed, recurrent, and control peritonitis occurred in 356, 165, and 2,021 patients, respectively. Coagulase-negative staphylococci and Staphylococcus aureus accounted for 48% of relapsing peritonitis (adjusted OR, 1.26 [95% CI, 0.94-1.70] and 1.54 [95% CI, 1.08-2.19], respectively), but were much less likely to be isolated in recurrent peritonitis. Recurrent peritonitis was associated more frequently with fungi (13%; OR, 2.16; 95% CI, 1.12-4.17). The empirical antimicrobial approaches to relapsing and recurrent peritonitis were similar and their subsequent clinical outcomes were comparable. Compared with uncomplicated peritonitis, relapsed and recurrent peritonitis were associated with higher rates of catheter removal (22% vs 30% vs 37%, respectively; P < 0.001) and permanent hemodialysis therapy transfer (20% vs 25% vs 32%; P < 0.001), but similar rates of hospitalization (73% vs 70% vs 70%) and death (2.8% vs 2.0% vs 1.2%). LIMITATIONS: Limited covariate adjustment. Residual confounding and coding bias could not be excluded. CONCLUSIONS: Relapsed and recurrent peritonitis are caused by different spectra of micro-organisms, but are not readily clinically distinguishable at presentation. Empirical treatment with broad-spectrum antibiotics and subsequent adjustment according to antimicrobial susceptibilities results in similar clinical outcomes, albeit with appreciably higher rates of catheter removal and hemodialysis therapy transfer than for uncomplicated peritonitis.

End-stage kidney disease due to scleroderma--outcomes in 127 consecutive ANZDATA registry cases.

BACKGROUND: Scleroderma is an uncommon cause of end-stage kidney disease (ESKD) which carries significant morbidity and mortality risks. The aim of this study was to determine the prevalence, treatment and outcomes of scleroderma patients with ESKD. METHODS: A study was conducted of all ESKD patients enrolled in the ANZDATA registry, who commenced dialysis between 15 May 1963 and 31 December 2005, and remained on dialysis for at least 90 days. RESULTS: Of the 40 238 patients who commenced dialysis during the study period, 127 (0.3%) patients had ESKD secondary to scleroderma. Scleroderma ESKD patients were more likely than other ESKD patients to be female (72% versus 43%, P < 0.001), Caucasian (98% versus 79%, P < 0.001) and of lower BMI (22.7 ± 4.7 versus 26.0 ± 5.9, P < 0.001) with a higher prevalence of chronic lung disease (36 versus 14%, P < 0.001) and lower prevalence of diabetes mellitus (10% versus 32%, P < 0.001) and coronary artery disease (23% versus 35%, P = 0.01). Median survival was significantly shorter in scleroderma ESKD (2.43 years, 95% confidence interval (CI) 1.75-3.11 years) than other ESKD (6.02 years, 95% CI 5.89-6.14 years, log-rank score 55.7, P < 0.001). Renal recovery was more likely in scleroderma patients (10% versus 1%, P < 0.001) with a shorter time to recovery. Scleroderma was found to be an independent predictor for mortality (HR 2.47, 95% CI 1.99-3.05) and renal recovery (HR 11.1, 95% CI 6.37-19.4). Five year deceased donor and live donor renal allograft survival rates of recipients with scleroderma were 53 and 100%, respectively. CONCLUSIONS: Scleroderma is an uncommon cause of ESKD, which is associated with increased risks of both spontaneous renal recovery and mortality.