Bhadran Bose

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.

The Outcomes of Patients with ESRD and ANCA-Associated Vasculitis in Australia and New Zealand

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.

Effect of dialysis modality on survival of hepatitis C-infected ESRF patients.

BACKGROUND AND OBJECTIVES Hepatitis C virus (HCV) infection is associated with increased mortality and morbidity in end-stage renal failure (ESRF) patients. Despite a lower incidence and risk of transmission of HCV infection with peritoneal dialysis (PD), the optimal dialysis modality for HCV-infected ESRF patients is not known. The aim of this study was to evaluate the impact of dialysis modality on the survival of HCV-infected ESRF patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study included all adult incident ESRF patients in Australia and New Zealand who commenced dialysis between January 1, 1994, and December 31, 2008, and were HCV antibody-positive at the time of dialysis commencement. Time to all-cause mortality was compared between hemodialysis (HD) and PD according to modality assignment at day 90, using Cox proportional hazards model analysis. RESULTS A total of 424 HCV-infected ESRF patients commenced dialysis during the study period and survived for at least 90 days (PD n = 134; HD n = 290). Mortality rates were comparable between PD and HD in the first year (10.7 versus 13.8 deaths per 100 patient-years, respectively; adjusted hazard ratio [HR] 0.65, 95% CI 0.34 to 1.26) and thereafter (20 versus 15.9 deaths per 100 patient-years, respectively; HR 1.27, 95% CI 0.86 to 1.88). CONCLUSIONS The survival of HCV-infected ESRF patients is comparable between PD and HD.

SCEDOSPORIUM APIOSPERMUM PERITONITIS IN A PATIENT UNDERGOING PERITONEAL DIALYSIS

To the Editor: Renal interstitial fibrosis (RIF) plays a most important role in the progression of renal diseases to end-stage renal failure. Unilateral ureteral obstruction (UUO) model was used extensively as a model of progressive RIF, accompanied by rapid parenchymal deterioration. All-trans retinoic acid (ATRA), a natural derivative of vitamin A, plays an important role in the prevention of fibrosis. However, there was a rare report investigating the effect of ATRA on RIF. Interestingly, Kishimoto et al. performed an investigation on the association of ATRA treatment with RIF progression in UUO model mice, and found that a significant improvement was observed in histological and immunological findings in the ATRA treatment group, including macrophage infiltration and improved expression of monocyte chemotactic protein-1, transforming growth factor-b1 (TGF-b1), a-smooth muscle actin (a-SMA) and collagen I compared with the UUO model group. They drew a conclusion that ATRA treatment was not only an effective prophylactic strategy, but also a therapeutic strategy for the treatment of progressive renal fibrosis in diseased kidneys. We also performed an investigation on the association of the ATRA treatment with RIF progression. The rats were divided into three groups: sham operation group (SHO), group of UUO model (GU) and UUO model group treated with ATRA (GA). The UUO model was established, and the rats in the GA group were treated with ATRA (Sigma, St. Louis, MO, USA; 15 mg/kg per day) in corn oil once daily by oral gavage, from the first day before operation. Rats in the GU and SHO groups were administrated saline. Rats from the three groups were killed 14 and 28 days after surgery, and the renal tissue was collected for the determination of histological and molecular biology. In our study, we found that ATRA treatment could significantly reduce the expressions of TGF-b1, a-SMA, collagen IV and fibronectin. Our results were similar with those from Kishimoto et al. So, ATRA might become a useful therapeutic strategy for the treatment of progressive renal fibrosis. All-trans retinoic acid might play an important role in the administration of renal diseases in experimental studies. In our previous study, we found that ATRA could alleviate glomerulosclerosis lesion in glomerulosclerosis rats induced by adriamycin. ATRA might be a candidate drug for the treatment of renal diseases in a clinical setting. However, further investigation should be performed in experimental animal models and the effect of ATRA should be confirmed in the clinical practice.

Arterial line versus venous line administration of low molecular weight heparin, enoxaparin for prevention of thrombosis in the extracorporeal blood circuit of patients on haemodialysis or haemodiafiltration: A randomized cross-over trial.

The objective of the study is to compare the anti‐factor Xa (AXa) level in the blood, after arterial and venous line administration of equivalent doses of enoxaparin for prevention of thrombosis in the extracorporeal blood circuit.

Transplantation Antigens and Histocompatibility Matching

The presence of donor-specific HLA antibodies in kidney transplant recipients can be identi‐ fied by crossmatch. Since 1969, pre-transplant crossmatch has become a mandatory component of the transplant work-up process. It has largely eliminated hyperacute rejection. Crossmatch techniques have expanded from basic complement-dependent microcytotoxicity (CDC) assays to additionally include flow crossmatches and virtual crossmatches derived using the luminex assay. The improved sensitivity and specificity of virtual crossmatch when compared to CDC and flow crossmatches has revolutionised the pre-transplant crossmatch process, but also greatly increased its complexity.

Post Transplant Anaemia

Anaemia, as a complication of end stage kidney disease (ESKD), is well studied (Eschbach and Adamson 1985). Reports indicate that anaemia in this patient population is associated with numerous morbidities, but predominantly cardiovascular complications such as left ventricular hypertrophy and heart failure (Wizemann, Schafer et al. 1993; Harnett, Foley et al. 1995). Contrary to the ample data available regarding anaemia in ESKD population, much less is known about the epidemiology of post-transplant anaemia (PTA), and only few studies have systematically investigated this issue (Saito, Fujiwara et al. 1998; Yorgin, Scandling et al. 2002; Mix, Kazmi et al. 2003; Vanrenterghem, Ponticelli et al. 2003). A successful renal allograft will correct not only the excretory functions of the kidney but also the endocrine functions (through the restored synthesis of erythropoietin and vitamin D) including the correction of anaemia. However, in the majority of transplant recipients, the renal graft does not function optimally. It is well known that renal excretory functions are not restored completely, but the extent to which renal endocrine functions are restored is only recently becoming better understood. A recent European survey of ten transplant centres revealed a prevalence of PTA as high as 42% (Molnar et al, 2011). PTA may occur at any time after renal transplantation. Early PTA (from the time of surgery until 3 months post-operatively) is most likely to be related to pre-transplant anaemia of ESKD, the surgery itself, iron deficiency, immunosuppression, inflammation or infection (Miles, Markell et al. 1997; Turkowski-Duhem, Kamar et al. 2005) or some combination of these. Later PTA is more likely to be related to consequences of long-term immunosuppression (particularly anti-metabolite medications) or a failing allograft. All the published large scale studies to date have focused mainly on late PTA (Miles, Markell et al. 1997; Vanrenterghem, Ponticelli et al. 2003; Turkowski-Duhem, Kamar et al. 2005), and there are a lack of studies looking at the management of early PTA, in particular, the optimal management of iron deficiency at the time of kidney transplantation. The importance of PTA is that it is one of the commonest complications after kidney transplantation, that it is strongly associated with cardiovascular morbidity (the primary cause of death of kidney transplant recipients, accounting for approximately one half of such deaths), and that its optimal treatment, either with iron, erythropoietin, or other agents, has yet to be determined by large-scale randomised controlled trials.