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.
Highlights
Because low glomerular filtration rate (GFR) leads to hyperuricemia, chronic kidney disease (CKD) is associated with hyperuricemia and gout [4]
We accepted any estimate of GFR, whether derived from serum creatinine and demographic variables, or from directly-measured creatinine or isotope clearance
Primary electronic database searches identified 5994 citations, which was reduced to 5497 citations by deduplication
Summary
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. Patients with CKD have higher mortality rates and reduced quality of life relative to the general population [2]. They are at a disproportionally higher cardiovascular risk, and most patients with CKD die of cardiovascular disease (CVD) rather than progress to end-stage renal disease (ESRD) [3]. CKD progression or reduce cardiovascular risk cannot be understated. Hyperuricemia has consistently been associated with incident CKD, though its association with progression of CKD has been less clear [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]
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