Abstract
Background and objectivesThe effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD.Design, setting, participants, and measurementsAccording to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used.ResultsSixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31–64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17–62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50–1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86–6.35) and the standardized mean differences in the change in proteinuria or albuminuria (−0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, −0.43 to −0.04) were also statistically significant.ConclusionsUric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.
Highlights
Chronic kidney disease (CKD) is a severe public health challenge
Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% confidence intervals (CIs)], 31–64) for kidney failure events (P < 0.001), and a 60% RR reduction for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50–1.46)
The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86–6.35) and the standardized mean differences in the change in proteinuria or albuminuria (−0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, −0.43 to −0.04) were statistically significant
Summary
Chronic kidney disease (CKD) is a severe public health challenge. The unfavorable impact of CKD includes progression to end-stage renal disease (ESRD), and increased risk of all-cause mortality and cardiovascular disease [1,2,3]. Uric acid-lowering therapy has been reported to delay the progression of kidney disease and/or reduce cardiovascular risk in patients with CKD [11,12,13] in several randomized controlled trials (RCTs). Two published meta-analyses have provided evidence of the relation between uric acidlowering therapy and changes in the estimated glomerular filtration rate (eGFR) in populations with CKD; the results were discordant [18, 19]. Both overviews did not evaluate the effects of uric acid-lowering therapy on dichotomous outcomes, including clinical kidney failure and cardiovascular events. Editor: Antonio Carlos Seguro, Universidade de Sao Paulo Faculdade de Medicina, BRAZIL
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