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Uric acid lowering therapies for preventing or delaying the progression of chronic kidney disease.

BACKGROUND
Non-randomised data have shown a link between hyperuricaemia and the progression or development of chronic kidney disease (CKD). If this is correct, urate lowering therapy might form an important part of chronic kidney disease care, reducing risks for cardiovascular outcomes and end-stage kidney disease.


OBJECTIVES
This review aims to study the benefits and harms of uric acid lowering therapy on the progression of CKD and other cardiovascular endpoints.


SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 20 July 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.


SELECTION CRITERIA
All randomised controlled trials testing primary urate lowering therapy in patients with or without CKD.


DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) if different scales were used.


MAIN RESULTS
Twelve studies (1187 participants) were included in the review. Risk of bias was unclear for the majority of domains in each study.Uric acid lowering therapy may make little or no difference in death at six months (2 studies, 498 participants: RR 1.66, 95% CI 0.61 to 4.48) or two years (2 studies, 220 participants): RR 0.13, 95% CI 0.02 to 1.06) (low certainty evidence). Uric acid lowering therapy may make little of no difference (low certainty evidence) in the incidence of ESKD at one or two years. Kidney function may be improved by uric acid lowering therapy at one year with a reduction in serum creatinine (2 studies, 83 participants: MD -73.35 µmol/L, 95% CI -107.28 to -39.41) and a rise in eGFR (1 study, 113 participants: MD 5.50 mL/min/1.73 m2, 95% CI 0.59 to 10.41). However it probably makes little or no difference to eGFR at two years (2 studies, 164 participants: MD 4.00 mL/min, 95% CI -3.28 to 11.28). Uric acid lowering therapy reduced uric acid levels at all time points (3, 4, 6, 12 and 24 months) (high certainty evidence).There is insufficient evidence to support an effect on blood pressure, proteinuria or other cardiovascular markers by uric acid lowering therapy. It should be noted that the apparent benefits of treatment were not apparent at all time points, introducing the potential for bias.


AUTHORS' CONCLUSIONS
There is limited data which suggests uric acid lowering therapy may prevent progression of chronic kidney disease but the conclusion is very uncertain. Benefits were not observed at all time points and study quality was generally low. Larger studies are required to study the effect of uric acid lowering therapy on CKD progression. Three ongoing studies will hopefully provide much needed high quality data.