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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pathogenic role in experimental crescentic glomerulonephritis (GN). Renal expression of MIF is also upregulated in human GN and correlates with leukocytic infiltration, histologic damage, and renal dysfunction. The study presented here examined whether MIF can be measured in urine and if so, whether the urine MIF concentration reflects the degree of renal injury. Urine and serum MIF was measured by enzyme-linked immunosorbent assay in 10 normal healthy volunteers and in a cohort of 63 patients with GN (2 thin basement membrane disease [TBM], 15 membranous GN, 10 focal segmental glomerular sclerosis, 20 IgA glomerularnephritis, 11 crescentic GN, 10 systemic lupus erythematosis World Health Organization class IV). Renal MIF expression was assessed by immunostaining of biopsy tissue. MIF was detected in urine from normal volunteers (mean+/-SD; 191+/-132 pg MIF/+/-mol creatinine). The urine MIF concentration was unchanged in patients with nonproliferative nephropathies (343 +/- 397 pg MIF/+/-mol Cr) but was increased 3.4-fold in proliferative nephropathies (645+/-527 pg MIF/mumol Cr; P < 0.05 versus normal and nonproliferative). Stratified analysis showed the greatest increase in urine MIF in crescentic GN (4.5-fold). In contrast, serum MIF levels were not different between normal patients and any patient group. Immunostaining demonstrated a significant increase in renal MIF expression in proliferative glomerulonephritides that was associated with macrophage and T cell infiltration. There was a significant correlation between the urine MIF concentration and renal MIF expression, but not with serum MIF, indicating a renal origin for the excreted urine MIF. The urine MIF concentration also correlated with the degree of renal dysfunction, histologic damage, and leukocytic infiltration, but not with the amount of proteinuria. In conclusion, this study shows that the urine MIF concentrati

The International Society of Nephrology (ISN) established the Young Nephrologists Committee (YNC) in 2007 to increase the awareness of the ISN mission and activities among younger nephrologists and thus increase their involvement. One of the primary aims of the YNC is to empower young nephrologists from developing countries by providing education and mentoring support. This is being achieved by establishing ISN YN workshops in the developing world for junior medical staff and nephrology trainees, with local younger nephrologists supervising the workshops. Mentoring is important for young nephrologists, and the ISN YNC have established a mentoring program through the ISN where mentors and the mentored are matched, and also meet-the professor sessions at ISN Nexus conferences. Research is being encouraged by establishing the World Congress of Nephrology Young Nephrology awards in basic and clinical science from the developing and developed world, allowing young nephrologists the opportunity to attend the WCN and present their work in plenary sessions. Another important focus of the ISN YNC has been to raise the awareness of ISN activities and their relevance to young nephrologists in the developing world. In conclusion, the ISN YNC is hoping to empower young nephrologists from developing countries and this will improve the prevention, diagnosis, and treatment of kidney disease worldwide.Copyright © 2013 International Society of Nephrology

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. METHOD(S): 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. RESULT(S): 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. CONCLUSION(S): In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment

Background: Peritoneal dialysis (PD) is recommended for adults with residual kidney function and without significant comorbidities. However, peritonitis is a serious and common complication that is associated with hospitalization, pain, catheter loss, and death. This study aims to describe the beliefs, needs, and experiences of PD patients about peritonitis, to inform the training, support, and care of these patients. eMethods: Qualitative semi-structured interviews were conducted with 29 patients from 3 renal units in Australia who had previous or current experience of PD. The interviews were conducted between November 2014 and November 2015. Transcripts were analyzed thematically. uResults: We identified 4 themes: constant vigilance for prevention (conscious of vulnerability, sharing responsibility with family, demanding attention to detail, ambiguity of detecting infection, ineradicable inhabitation, jeopardizing PD success); invading harm (life-threatening, wreaking internal damage, debilitating pain, losing control and dignity); incapacitating lifestyle interference (financial strain, isolation and separation, exacerbating burden on family); and exasperation with hospitalization (dread of hospital admission, exposure to infection, gruelling follow-up schedule, exposure to harm). eConclusions: Patients perceived that peritonitis could threaten their health, treatment modality, and lifestyle, which motivated vigilance and attention to hygiene. They felt a loss of control due to debilitating symptoms including pain and having to be hospitalized, and they were uncertain about how to monitor for signs of peritonitis. Providing patients with education about the causes and signs of peritonitis and addressing their concerns about lifestyle impact, financial impact, hospitalization, and peritonitis-related anxieties may improve treatment satisfaction and outcomes for patients requiring PD.Copyright © 2016 International Society for Peritoneal Dialysis.

Background. Alport syndrome is a rare inheritable renal disease. Clinical outcomes for patients progressing to endstage 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 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.

Objectives: To study the body mass index (BMI) trajectory in patients with incident end-stage kidney disease and its association with all-cause mortality. Method(s): This longitudinal cohort study included 17022 adult patients commencing hemodialysis [HD] (n=10860) or peritoneal dialysis [PD] (n=6162) between 2001 and 2008 and had >=6-month follow-up and >=2 weight measurements, using the Australia and New Zealand Dialysis and Transplant Registry data. The association of time-varying BMI with all-cause mortality was explored using multivariate Cox regression models. Result(s): The median follow-up was 2.3 years. There was a non-linear change in the mean BMI (kg/m2) over time, with an initial decrease from 27.6 (95% confidence interval [CI]: 27.5, 27.7) to 26.7 (95% CI: 26.6, 26.9) at 3-month, followed by increments to 27.1 (95% CI: 27, 27.2) at 1-year and 27.2 (95% CI: 26.8, 27.1) at 3-year, and a gradual decrease subsequently. The BMI trajectory was significantly lower in HD patients who died than those who survived, although this pattern was not observed in PD patients. Compared to the reference time-varying BMI category of 25.1-28 kg/m2, the mortality risks of both HD and PD patients were greater in all categories of time-varying BMI <25 kg/m2. The mortality risks were significantly lower in all categories of time-varying BMI >28.1 kg/m2 among HD patients, but only in the category 28.1-31 kg/m2 among PD patients. Conclusion(s): BMI changed over time in a non-linear fashion in incident dialysis patients. Time-varying measures of BMI were significantly associated with mortality risk in both HD and PD patients.Copyright © 2014 Badve et al.

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.Copyright © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background: The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. Method(s): The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. Result(s): Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon gamma-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. Conclusion(s): Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary biomarkers as t

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. Method(s): 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. Result(s): 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 respec-tively in their allograft. Conclusion(s): 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.Copyright © 2015 S. Karger AG, Basel.

Background: The aim of the present study was to investigate the relationship between socio-economic status (SES) and peritoneal dialysis (PD)-related peritonitis. Method(s): Associations between area SES and peritonitis risk and outcomes were examined in all non-indigenous patients who received PD in Australia between 1 October 2003 and 31 December 2010 (peritonitis outcomes). SES was assessed by deciles of postcode-based Australian Socio-Economic Indexes for Areas (SEIFA), including Index of Relative Socio-economic Disadvantage (IRSD), Index of Relative Socio-economic Advantage and Disadvantage (IRSAD), Index of Economic Resources (IER) and Index of Education and Occupation (IEO). Result(s): 7,417 patients were included in the present study. Mixed-effects Poisson regression demonstrated that incident rate ratios for peritonitis were generally lower in the higher SEIFA-based deciles compared with the reference (decile 1), although the reductions were only statistically significant in some deciles (IRSAD deciles 2 and 4 - 9; IRSD deciles 4 - 6; IER deciles 4 and 6; IEO deciles 3 and 6). Mixed-effects logistic regression showed that lower probabilities of hospitalization were predicted by relatively higher SES, and lower probabilities of peritonitis-associated death were predicted by less SES disadvantage status and greater access to economic resources. No association was observed between SES and the risks of peritonitis cure, catheter removal and permanent hemodialysis (HD) transfer. Conclusion(s): In Australia, where there is universal free healthcare, higher SES was associated with lower risks of peritonitis-associated hospitalization and death, and a lower risk of peritonitis in some categories.Copyright © 2015 International Society for Peritoneal Dialysis.

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 m 2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity chi2 = 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 chi2 = 3, I 2 = 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. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background There are few reports regarding the long-term renal replacement therapy (RRT) outcomes of amyloidosis.MethodsIn 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.ResultsOf 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%.ConclusionsAmyloidosis 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. © 2012 The Author.

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. Result(s): 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). Conclusion(s): 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. © 2012 Tang et al.; licensee BioMed Central Ltd.

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. © 2012 International Society of Nephrology.

Background and objectives this study aimed to evaluate dialysis and transplant outcomes of patients with ESRD secondary to ANCA-associated vasculitis (AAV). Design, setting, participants, & measurements All ESRD patients who commenced renal replacement therapy in Australia and New Zealand between 1996 and 2010 were included. Outcomes were assessed by Kaplan-Meier, multivariable Cox regression, and competing-risks regression survival analyses. Results Of 36,884 ESRD patients, 228 had microscopic polyangiitis (MPA) and 221 had granulomatosis with polyangiitis (GPA). Using competing-risks regression, compared with other causes of ESRD, MPA patients (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.73-1.08; P=0.24) and GPA patients (HR, 0.94; 95% CI, 0.74-1.19; P=0.62) experienced comparable survival on dialysis. Forty-six MPA patients (21%) and 47 GPA (20%) patients received 98 renal allografts. Respective 10-year first graft survival rates in MPA, GPA, and non-AAV patients were 50%, 62%, 70%, whereas patient survival rates were 68%, 85% and 83%, respectively. Compared with non-AAV patients, MPA transplant recipients had higher risks of graft failure (HR, 1.87; 95% CI, 1.07-3.25; P=0.03) and death (HR, 1.94; 95% CI, 1.02-3.69; P=0.04), whereas GPA transplant recipients experienced comparable renal allograft survival (HR, 0.91; 95% CI, 0.43-1.93; P=0.81) and patient survival (HR, 0.58; 95% CI, 0.23-2.27; P=0.58). AAV recurrence was observed in two renal allografts (2%). Conclusions Compared with ESRD patients without AAV, those with GPA have comparable renal replacement therapy outcomes, whereas MPA patients have comparable dialysis survival but poorer renal transplant allograft and patient survival rates. © 2013 by the American Society of Nephrology.

Staphylococcus aureus peritonitis is a serious complication of peritoneal dialysis (PD). Since reports of the course and treatment of S. aureus peritonitis have generally been limited to small, single-center studies, the aim of the current investigation was to examine the frequency, predictors, treatment, and clinical outcomes of this condition in all 4675 patients receiving PD in Australia between 1 October 2003 and 31 December 2006. 3594 episodes of peritonitis occurred in 1984 patients and 503 (14%) episodes of S. aureus peritonitis occurred in 355 (8%) individuals. 273 (77%) patients experienced 1 episode of S. aureus peritonitis, 52 (15%) experienced 2 episodes, 19 (5%) experienced 3 episodes, and 11 (3%) experienced 4 or more episodes. The predominant antibiotics used as initial empiric therapy were vancomycin (61%) and cephazolin(31%). Once S. aureus was isolated and identified, the prescription of vancomycin did not appreciably change for methicillin-sensitive S. aureus (MSSA) peritonitis (59%) and increased for methicillin-resistant S. aureus (MRSA) peritonitis (84%). S. aureus peritonitis was associated with a higher rate of relapse than non-S. aureus peritonitis (20% vs 13%, p < 0.001) but comparable rates of hospitalization (67% vs 70%, p = 0.2), catheter removal (23% vs 21%, p = 0.4), hemodialysis transfer (18% vs 18%, p = 0.6), and death (2.2% vs 2.3%, p = 0.9). MRSA peritonitis was independently predictive of an increased risk of permanent hemodialysis transfer [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.17 - 3.82] and tended to be associated with an increased risk of hospitalization (OR 2.00, 95% CI 0.96 - 4.19). The initial empiric antibiotic choice between vancomycin and cephazolin was not significantly associated with clinical outcomes, but serious adverse outcomes were more likely if vancomycin was not used for subsequent treatment of MRSA peritonitis. In conclusion, S. aureus peritonitis is a serious complication of PD, involves a smal

BackgroundThe 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.MethodsAdult, 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.ResultsOf 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. ConclusionsBiocompatible 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 me

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. © 2012 International Society of Nephrology.

We analyzed data from the Australia and New Zealand Dialysis and Transplant Registry for 1 October 2003 to 31 December 2008 with the aim of describing the nature of peritonitis, therapies, and outcomes in patients on peritoneal dialysis (PD) in Australia. At least 1 episode of PD was observed in 6639 patients. The overall peritonitis rate was 0.60 episodes per patient-year (95% confidence interval: 0.59 to 0.62 episodes), with 6229 peritonitis episodes occurring in 3136 patients. Of those episodes, 13% were culture-negative, and 11% were polymicrobial. Gram-positive organisms were isolated in 53.4% of single-organism peritonitis episodes, and gram-negative organisms, in 23.6%. Mycobacterial and fungal peritonitis episodes were rare. Initial antibiotic therapy for most peritonitis episodes used 2 agents (most commonly vancomycin and an aminoglycoside); in 77.2% of episodes, therapy was subsequently changed to a single agent. Tenckhoff catheter removal was required in 20.4% of cases at a median of 6 days, and catheter removal was more common in fungal, mycobacterial, and anaerobic infections, with a median time to removal of 4 - 5 days. Peritonitis was the cause of death in 2.6% of patients. Transfer to hemodialysis and hospitalization were frequent outcomes of peritonitis. There was no relationship between center size and peritonitis rate. The peritonitis rate in Australia between 2003 and 2008 was higher than that reported in many other countries, with a particularly higher rate of gram-negative peritonitis. © 2011 International Society for Peritoneal Dialysis.

Background: Human peritoneal mesothelial cells (HPMC) are useful for the analysis of peritoneal reactions to various insults and to peritoneal dialysate. HPMC can be readily obtained from spent dialysis fluid, but leucocyte contamination is a major problem when using these cells for in vitro experiments. Therefore, we examined the persistence of leucocyte contamination in HPMC cultures obtained from spent dialysate. Method(s): Cells were obtained from spent patient dialysate bags by centrifugation and analysed for specific cell phenotypes by flow cytometry at the initial collection and during sequential passages in cell culture. Cell proliferation was assessed by either bromodeoxyuridine incorporation or a dehydrogenase assay. Cytokine secretion was analysed by enzyme-linked immunosorbent assay. Result(s): Spent dialysate bags contained two major cell populations: CD45+ leucocytes and cytokeratin-8/18+ cells. Initially, most collected cells were CD45+, but their numbers decreased rapidly during the first week of culture. However, a persistent contamination of CD45+ leucocytes, approximately 20% of cells, was evident during the next three passages. This persistent CD45+ contamination was identified as CD68+ macrophages and contained bromodeoxyuridine + proliferating cells. These macrophages could be removed by fluorescence-activated cell sorting using anti-CD45 antibody, resulting in highly purified HPMC which expressed cytokeratin-8/18 and calretinin. Supernatant obtained from these purified HPMC contained macrophage colony stimulating factor and induced proliferation of bone marrow-derived macrophages. Conclusion(s): Spent dialysate contains macrophages which persist in culture and are associated with HPMC secretion of macrophage colony stimulating factor and macrophage proliferation. Therefore, contaminating macrophages should be specifically removed from HPMC preparations before performing in vitro studies. © 2007 The Authors.

Background. High transporter status is associated with reduced survival of patients receiving peritoneal dialysis (PD). This may be due primarily to the development of complications related to the PD process, in which case the survival disadvantage may not persist following transfer to haemodialysis (HD). In this study, we aimed to assess the impact of peritoneal membrane transporter status on patient survival and the likelihood of return to PD following transfer from PD to HD. Methods. The Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry was searched to identify all patients between 1 April 1999 and 31 March 2004 who had received PD and subsequently transferred to HD, in whom an incident 4 h dialysate: plasma creatinine ratio was recorded. A Cox proportional hazards model was used to identify factors significantly associated with patient and technique survival after commencement of HD. Results. A total of 918 patients were included in the analysis. On multivariate Cox regression analysis there was no difference in survival between transport groups relative to the reference group of low average transporters (adjusted hazard ratio (HR) 0.71, 95% CI 0.42-1.19, P = 0.19, HR 0.94, 95% CI 0.63-1.38, P = 0.73 and HR 0.24, 95% CI 0.06-1.01, P = 0.051 for high, high average and low transporter groups, respectively). Significant predictors of mortality were duration of PD more than 22 months (HR 2.32, 95% CI 1.24-4.33, P = 0.01), increasing age, late referral to a nephrologist and a history of diabetes mellitus. The likelihood of returning to PD was increased if initial PD technique failure was due to mechanical complications compared with all other causes of failure [HR 3.65 (95% CI 2.78-4.79) P < 0.001] and decreased with higher body mass index [HR 0.97 per kg/m2 (95% CI 0.94-0.99), P = 0.01] and the 4 h dialysate: plasma creatinine ratio considered as a continuous variable [4 h D:P Cr; HR 0.32 per unit (95% CI 0.12-0.89), P = 0.03]. Conclusions. The su

Background: The number of elderly patients with end-stage kidney disease (ESKD) is increasing worldwide, but the proportion of elderly patients commencing peritoneal dialysis (PD) is falling. The reluctance of elderly ESKD patients to consider PD may be related to a perception that PD is associated with greater rates of complications. In the present study, we compared outcomes between younger and older PD patients. Method(s): Using Australia and New Zealand Dialysis Registry data, all adult ESKD patients commencing PD between 1991 and 2007 were categorized into under 50, 50 - 64.9, and 65 years of age or older groups. Time to first peritonitis, death-censored technique failure, and peritonitis-associated and all-cause mortality were evaluated by multivariate Cox proportional hazards model analysis. Result(s): Of the 12 932 PD patients included in the study, 3370 (26%) were under 50 years of age, 4386 (34%) were 50 - 64.9 years of age, and 5176 (40%) were 65 years of age or older. Compared with younger patients (<50 years), elderly patients (>=65 years) had a similar peritonitis-free survival and a lower risk of death-censored technique failure [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.79 to 0.93], but they had higher peritonitis-related (HR: 2.31; 95% CI: 1.68 to 3.18) and all-cause mortality (HR: 2.90; 95% CI: 2.60 to 3.23). Conclusion(s): Not unexpectedly, elderly patients have higher peritonitis-related and all-cause mortality, which is likely a consequence of a greater prevalence of comorbid disease. However, compared with younger patients, elderly patients have superior technique survival and similar peritonitis-free survival, suggesting that PD is a viable renal replacement therapy in this group of patients. © 2011 International Society for 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 themagnitude of this association wasmuch 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 themagnitude is greater during the initial 30 days. Copyright © 2012 by the American Society of Nephrology.

Objective: To compare injection site pain of subcutaneous (sc) epoetin beta and darbepoetin alfa in adult patients with chronic kidney disease. Research design and methods: This was a multi-centre, randomised, two-arm, single-blind, cross-over study. Patients were randomised to receive weekly sc darbepoetin alfa 30 mug or weekly sc epoetin beta 6000 IU for 2 weeks and were then crossed over to the alternative treatment for 2 weeks. Injection site pain was assessed using a 10 cm ungraduated visual analogue scale (0 = no pain, 10=worst pain) and a six-point verbal rating scale. Patient preference for treatment was also assessed. Trial registration: http://clinicaltrials.gov/(NCT00377481). Result(s): All randomised patients (N=48) completed the study. The sample comprised 29 chronic kidney disease patients (Stage 3 or Stage 4), 11 peritoneal dialysis patients and 8 renal transplant patients. Patients perceived significantly less pain with epoetin beta than darbepoetin alfa, using the visual analogue scale (relative pain score=2.75, darbepoetin alfa:epoetin beta, 95% Cl: 1.85, 4.07; p<0.0001) and the verbal rating scale (median: 0.5, 95% Cl: 0.5, 1.0 vs. median: 1.5, 95% Cl: 1.0, 2.0; p<0.0001). Epoetin beta was preferred by significantly more patients (65%) than darbepoetin alfa (10%) (p<0.001); 25% of patients reported no preference. Conclusion(s): Limitations included lack of an epoetin alfa comparator and limited blinding (patients were blinded to treatment, however, an unblinded nurse administered treatment). We show that sc injection of epoetin beta is significantly less painful than darbepoetin alfa and patient preference for epoetin beta confirms that the difference is clinically meaningful. © 2008 Informa UK Ltd. All rights reserved.

{black diamond suit} Background: A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products ("biocompatible") compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. {black diamond suit} Methods: Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. {black diamond suit} Results: The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-rel

Background. There is limited information about the outcomes of patients commencing peritoneal dialysis (PD) after failed kidney transplantation. The aim of the present study was to compare patient survival, death-censored technique survival and peritonitis-free survival between patients initiating PD after failed renal allografts and those after failed native kidneys. Methods. The study included all patients from the ANZDATA Registry who started PD between April 1, 1991 and March 31, 2004. Times to death, death-censored technique failure and first peritonitis episode were examined by multivariate Cox proportional hazards models. For all outcomes, conditional risk set models were utilized for the multiple failure data, and analyses were stratified by failure order. Standard errors were calculated by using robust variance estimation for the cluster-correlated data. Results. In total, 13 947 episodes of PD were recorded in 23 579 person-years. Of these, 309 PD episodes were started after allograft failure. Compared with PD patients who had never undergone kidney transplantation, those with failed renal allografts were more likely to be younger, Caucasian, New Zealand residents and life-long non-smokers with lower body mass index (BMI), poorer initial renal function and a longer period from commencement of the first renal replacement therapy to PD. On multivariate analysis, PD patients with failed kidney transplants had comparable patient mortality [weighted hazards ratio (HR) 1.09, 95% confidence interval (CI) 0.81-1.45, P=0.582], death-censored technique failure (adjusted HR 0.91, 95% CI 0.75-1.10, P=0.315) and peritonitis-free survival (adjusted HR 0.92, 95% CI 0.72-1.16, P=0.444) with those PD patients who had failed native kidneys. Similar findings were observed in a subset of patients (n= 5496) for whom peritoneal transport status was known and included in the models as a covariate. Conclusion. Patients commencing PD after renal allograft failure experienced outco

Recent studies have identified a key role for macrophage migration inhibitory factor (MIF) in a number of immune cell-mediated diseases. The current study investigated the potential role of MIF in acute allograft rejection. Lewis rats underwent bilateral nephrectomy and then received an orthotopic DA renal allograft or an orthotopic Lewis renal isograft. Groups of six animals were killed at day 1 or 5 after transplantation. No immunosuppression was used. Animals receiving a renal allograft exhibited severe rejection on day 5, as shown by high levels of serum creatinine, very low rates of creatinine clearance, and severe tubulitis with a dense macrophage and T cell infiltrate. In contrast, isografts had normal renal function on day 5 with no histological evidence of rejection. Northern blotting showed that renal MIF mRNA expression was unchanged at day 1, but was increased 3.5-fold on day 5. In situ hybridization showed a marked increase in MIF mRNA expression by tubular cells and MIF mRNA expression by many infiltrating mononuclear cells in day 5 allografts. Immunostaining confirmed an increase in tubular MIF protein expression, particularly in areas of severe tubular damage with prominent leucocytic infiltration. Double staining showed that many infiltrating macrophages and T cells expressed the MIF protein in day 5 allografts. There was only a minor increase in MIF expression in day 5 isografts, demonstrating that neither surgical injury nor stress cause significant up-regulation of MIF expression in allograft rejection. In conclusion, this study has demonstrated that local MIF production is specifically increased in acute renal allograft rejection. These results suggest that MIF may play an important role in the cellular immune response mediating acute allograft rejection.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pathogenic role in experimental crescentic glomerulonephritis (GN). Renal expression of MIF is also upregulated in human GN and correlates with leukocytic infiltration, histologic damage, and renal dysfunction. The study presented here examined whether MIF can be measured in urine and if so, whether the urine MIF concentration reflects the degree of renal injury. Urine and serum MIF was measured by enzyme-linked immunosorbent assay in 10 normal healthy volunteers and in a cohort of 63 patients with GN (2 thin basement membrane disease [TBM], 15 membranous GN, 10 focal segmental glomerular sclerosis, 20 IgA glomerulamephritis, 11 crescentic GN, 10 systemic lupus erythematosis World Health Organization class IV). Renal MIF expression was assessed by immunostaining of biopsy tissue. MIF was detected in urine from normal volunteers (mean +/- SD; 191 +/- 132 pg MIF/mumol creatinine). The urine MIF concentration was unchanged in patients with nonproliferative nephropathies (343 +/- 397 pg MIF/mumol Cr) but was increased 3.4-fold in proliferative nephropathies (645 +/- 527 pg MIF/mumol Cr; P < 0.05 versus normal and nonproliferative). Stratified analysis showed the greatest increase in urine MIF in crescentic GN (4.5-fold). In contrast, serum MIF levels were not different between normal patients and any patient group. Immunostaining demonstrated a significant increase in renal MIF expression in proliferative glomerulonephritides that was associated with macrophage and T cell infiltration. There was a significant correlation between the urine MIF concentration and renal MIF expression, but not with serum MIF, indicating a renal origin for the excreted urine MIF. The urine MIF concentration also correlated with the degree of renal dysfunction, histologic damage, and leukocytic infiltration, but not with the amount of proteinuria. In conclusion, this study shows that the urine MIF concentr

Background. Infection due to Corynebacterium species has been reported with increasing frequency over recent decades. The impacts of enhanced laboratory detection together with widespread use of new peritoneal dialysis (PD) connection technology and antimicrobial prophylaxis strategies on Corynebacterium PD-associated peritonitis have not been well studied.Methods. We investigated the frequency, predictors, treatment and clinical outcomes of Corynebacterium peritonitis in all Australian adult patients involving 66 centres who were receiving PD between 1 October 2003 and 31 December 2006.Results. Eighty-two episodes of Corynebacterium peritonitis (2.3 of all peritonitis episodes) occurred in 65 (1.4) PD patients. Ten (15) patients experienced more than one episode of Corynebacterium peritonitis and additional organisms were isolated in 12 (15) episodes of Corynebacterium peritonitis. The incidence of Corynebacterium peritonitis was significantly and independently predicted only by BMI: RR 2.72 (95 CI 1.38-5.36) for the highest tertile BMI compared with the lowest tertile. The overall cure rate with antibiotics alone was 67, which was similar to that of peritonitis due to other organisms. Vancomycin was the most common antimicrobial agent administered in the initial empiric and subsequent antibiotic regimens, although outcomes were similar regardless of antimicrobial schedule. Corynebacterium peritonitis not infrequently resulted in relapse (18), repeat peritonitis (15), hospitalization (70), catheter removal (21), permanent haemodialysis transfer (15) and death (2). The individuals who had their catheters removed more than 1 week after the onset of Corynebacterium peritonitis had a significantly higher risk of permanent haemodialysis transfer than those who had their catheters removed within 1 week (90 versus 43, P < 0.05).Conclusions. Corynebacterium is an uncommon but significant cause of PD-associated peritonitis. Complete cure with antibiotics alone is possible i

Background. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is a potent activator of macrophages and T cells. Previous studies have shown that local MIF production is increased in acute renal allograft rejection, suggesting that it may play an important role in the rejection process. Aims. To determine if urine and serum MIF concentrations: (1) are increased in acute rejection, and (2) can be used as noninvasive tools to discriminate between acute rejection (AR) and cyclosporine nephrotoxicity (CyA toxicity). Methods. In a prospective study of nine renal allograft patients (five acute rejection and four stable), serial urine MIF concentrations were measured by ELISA in the first 14 days after transplantation. In a retrospective study, MIF concentrations in urine and serum were measured in 24 patients who were biopsied for acute renal transplant dysfunction (11 AR, 13 CyA toxicity). Urine and serum MIF were also measured in 23 stable renal transplant patients and 10 normals. Results. MIF was readily detected in the urine of normal healthy controls (106+/-61 pg/mumol creatinine). In the prospective study, the urinary MIF concentration was increased substantially on day 1 posttransplantation and subsequently fell in parallel with the serum creatinine. However, urine MIF increased before episodes of biopsy proven acute rejection. The retrospective study showed that urine MIF concentrations in patients with AR were increased 5-fold compared to normal controls (439+/-313 pg/mumol Cr; P<0.01). In contrast, urine MIF concentrations in CyA toxicity were not significantly different to normal controls (145+/-119 pg/mumol Cr; P=NS). A marked increase in MIF immunostaining was seen in biopsies of AR, but not in CyA toxicity. No significant differences were evident in serum MIF levels between normals and any transplant patient group. Conclusions. These results suggest that measurement of urine MIF concentration may be useful in monitoring renal tr

Background. Macrophage migration inhibitory factor (MIF) plays a pivotal role in immune-mediated diseases. Despite the long-standing association of MIF with the delayed-type hypersensitivity response, the potential role of MIF in allograft rejection is unknown. Methods. MIF expression was assessed by in situ hybridization and immunohistochemistry staining in 62 biopsies of human renal allograft rejection and in normal human kidney. Results. MIF mRNA and protein is constitutively expressed in normal kidney, being largely restricted to tubular epithelial cells, some glomerular epithelial cells, and vascular smooth muscle cells. In both acute and chronic renal allograft rejection, there was marked up-regulation of MIF mRNA and protein expression by intrinsic kidney cells such as tubular epithelial cells and vascular endothelial and smooth muscle cells. There was also MIF expression by infiltrating macrophages and T cells. Of note, macrophage and T cell infiltrates were largely restricted to areas with marked up-regulation of MIF expression, potentially contributing to the development of severe tubulitis and intimal or transmural arteritis. Quantitative analysis found that increased MIF expression in allograft rejection gave a highly significant correlation with macrophage and T cell accumulation in both the glomerulus and interstitium (P<0.001). In addition, the number of MIF+ tubules and interstitial MIF+ cells correlated significantly with the severity of allograft rejection (P<0.01), and the loss of renal function (P<0.01). In contrast, no up-regulation of renal MIF expression and no leukocyte accumulation was seen in allograft biopsies without evidence of rejection. Conclusions. This is the first study to demonstrate that local MIF expression is up-regulated during allograft rejection. The association between up- regulation of MIF expression, macrophage and T cell infiltration and the severity of renal allograft rejection suggests that MIF may be an important media

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: 20.22 and 20.28 ml/min per 1.73 m2 per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, 20.09 and 20.10 ml/min per 1.73 m2 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. Copyright © 2012 by the American Society of Nephrology.