Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis

Abstract

BackgroundHyperuricemia may contribute to renal injury. We do not know whether use of treatments that lower urate reduce the progression of chronic kidney disease (CKD) and cardiovascular disease. We performed a systematic review and meta-analysis of randomized controlled trials to assess the benefits and risks of treatments that lower urate in patients with stages 3-5 CKD.MethodsWe searched MEDLINE, EMBASE, CENTRAL, Web of Science and trial registers for randomized controlled trials (RCTs) without language restriction. Two authors independently screened articles, assessed risk of bias and extracted data. Data obtained included serum uric acid, serum creatinine or other estimates of glomerular filtration rate, incidence of end-stage renal disease (ESRD), systolic and diastolic blood pressure, proteinuria, cardiovascular disease and adverse events.ResultsFrom the 5497 citations screened, 19 RCTs enrolling 992 participants met our inclusion criteria. Given significant heterogeneity in duration of follow-up and study comparators, only trials greater than 3 months comparing allopurinol and inactive control were meta-analyzed using random effects models. Pooled estimate for eGFR was in favour of allopurinol with a mean difference (MD) of 3.2 ml/min/1.73 m2, 95% CI 0.16-6.2 ml/min/1.73 m2, p = 0.039 and this was consistent with results for serum creatinine. Statistically significant reductions in serum uric acid, systolic and diastolic blood pressure were found, favouring allopurinol. There were insufficient data on adverse events, incidence of ESRD and cardiovascular disease for analysis.ConclusionsAdequately powered RCTs are needed to establish whether treatments that lower urate have beneficial renal and cardiovascular effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0047-z) contains supplementary material, which is available to authorized users.

Overview of Allopurinol Decisions in Primary Care: A Narrative Review

“…Hyperuricaemia, a prerequisite for gout, is related to the metabolic syndrome and is an independent danger factor for chronic kidney illness, stroke and perhaps ischaemic heart disease .It is connected with multiple damaging health results, including hypertension, heart disease and is involved as 3910 an important facet of the metabolic syndrome [6] . Furthermore, hyperuricaemia is currently being considered as a modifiable danger element for deterioration of renal function [7] . The management of gout is complexed by the episodic nature of the disease.…”

The challenge of Mendelian randomization approach

“…Statistically significant reductions in serum uric acid, systolic, and diastolic blood pressure were found, favoring allopurinol, but there were insufficient data for analysis on adverse events, incidence of end stage renal disease (ESRD), and CV disease. The authors concluded that data are promising, but adequately powered randomized clinical trials are needed to establish whether treatments that lower urate have beneficial renal effects 10 . Observational studies were unable to capture the link between uric acid and CKD, because of methodological inadequacy.…”

“…Definitive evidence of a causal relationship of hyperuricemia with CKD has not been produced, and large-scale clinical trials testing the effect of urate lowering therapy on major clinical end-points of CKD progression are still lacking 9 . Recently, the efficacy and the risks of urate lowering therapy to improve outcomes in patients with CKD were evaluated by a systematic review of currently published studies, and a meta-analysis of results was carried out 10 .…”

Stop chronic kidney disease progression: Time is approaching

“…Treatment of CKD patients with estimated GFR of 40.6 ± 11.3 mL/min with allopurinol 100 mg/d was associated with significant decrease in renal events (need of dialysis, doubling of serum creatinine or > 50% reduction of GFR) and cardiovascular events in comparison to control CKD patients taking only their standard treatment (P < 0.004 and 0.02 respectively) [102] . In addition, a recent meta-analysis showed a significant favorable effect of allopurinol on the rate of GFR decline [103] . Another recent trial demonstrated the significant impact of febuxostat on CKD progression in stage G3 and G4 patients [104] .…”