Effectiveness of Urate-Lowering Therapy for Renal Function in Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials

Abstract

Background and Objective: Hyperuricemia is closely related to chronic kidney disease (CKD). The effects of urate-lowering therapy (ULT) on renal outcomes are uncertain, and whether it is warranted in CKD patients is currently unclear. The aim of our meta-analysis of randomized clinical trials (RCTs) was to assess the effectiveness and safety of ULT for improving kidney function in patients with CKD.Methods: RCTs were retrieved from the PubMed, Embase, MEDLINE and Cochrane Central Register of Controlled Trials databases. The meta-analysis was performed using Review Manager and Stata/SE software. The outcomes were changes in renal function and serum uric acid (SUA), serum creatinine, and adverse events.Results: Twelve RCTs with 1,469 participants were included in the meta-analysis. ULT was found to effectively lower SUA (standard mean difference (SMD): -2.70; 95% confidence interval (CI): -3.71, -1.69) but the renoprotective effects were not superior to those of control therapy (placebo or usual therapy), which were stable in the subgroup analyses and sensitivity analyses. Regarding adverse events, their risks did not increase in the ULT group compared with the control group and were stable in the sensitivity analyses.Conclusion: The findings of our meta-analysis suggested that ULT can effectively lower SUA, but there is insufficient evidence to support the renoprotective effects of ULT in CKD patients. In addition, ULT is safe for patients with CKD.Systematic Review Registration:https://clinicaltrials.gov/, identifier PROSPERO (CRD42020200550).

Uric Acid and Chronic Kidney Disease: Still More to Do

“…One might hope that meta-analyses might help resolve the issues, but even here there remains confusion, because some recent studies suggest that treatment of asymptomatic hyperuricemia in CKD does slow progression, 52 , 53 whereas others are mixed or indeterminant, 50 , 54 , 55 and some are negative. 56 Some meta-analyses show benefit with only specific urate-lowering drugs, such as febuxostat. 57 , 58 One possible explanation for the mixed data is that there may be subgroups that particularly benefit from treatment.…”

Association between serum uric acid level and systemic lupus erythematosus kidney outcome: An observational study in Southern Chinese population and a meta-analysis

“…To better explore the influence of SUA on SLE patients' kidney outcomes, the role of urate-lowering therapy in the development and progression of LN is necessary to be clarified. Several recently published large cohort studies on all-cause CKD [42][43][44][45][46][47][48] and diabetic kidney disease 49,50 patients suggest that urate-lowering with xanthine oxidase inhibitor therapy alone may not yield clinically significant kidney benefit. However, to the best of our knowledge, there was no existing study concerning the impact of urate-lowering therapy on LN patients.…”

Hyperuricemia and gout: effects on bone and articular cartilage (literature review)

“…При этом, по данным некоторых авторов, прогноз пациентов с ишемической болезнью сердца, хронической болезнью почек и артериальной гипертензией с ранним началом и персистирующей ГУ может улучшиться при назначении УСТ [58]. Однако, основываясь на одних только данных наблюдений, невозможно назначать регулярную лекарственную терапию, учитывая частое несоответствие между обсервационными исследованиями и рандомизированными контролируемыми исследованиями [59,60]. Предполагается, что для окончательного решения необходимы данные двойных слепых плацебо-контролируемых исследований, в которых изучалось бы влияние адекватных доз уратснижающих препаратов, длительность исследований превышала 3 года, а статистическая мощность была бы достаточной для выявления различий в частоте исследуемых событий не менее чем на 25% [60].…”