Efficacy of Urate-Lowering Therapy in Patients With Chronic Kidney Disease: A Network Meta-Analysis of Randomized Controlled Trials

Clin Ther. 2022 May;44(5):723-735.e6. doi: 10.1016/j.clinthera.2022.03.014. Epub 2022 May 22.

Abstract

Purpose: The goal of this study was to systematically review the efficacy and safety of urate-lowering therapy in patients with chronic kidney disease (CKD).

Methods: PubMed, the Cochrane Central Registration of Controlled Trials, and EMBASE databases and several websites were electronically searched to collect randomized clinical trials on the efficacy of urate-lowering therapy in CKD from inception to December 31, 2020. The key primary end points were uric acid or estimated glomerular filtration rate (eGFR) levels; the safety end points were death, renal event, cardiovascular event, and gastrointestinal event. A Bayesian network meta-analysis was conducted with the use of ADDIS and R software.

Findings: A total of 17 randomized clinical trials involving 2059 patients were included. The results of network meta-analysis showed that urate-lowering therapy could reduce urate levels in patients with CKD. Febuxostat was the most effective treatment in lowering urate levels according to the rank probability. Urate-lowering therapy has the tendency to delay the decline of eGFR, but the difference was not statistically significant. Ranking probability showed that benzbromarone, febuxostat, and allopurinol ranked higher than placebo in reducing the decline of eGFR. There were no statistically significant differences between groups in the incidence of all adverse effects.

Implications: All urate-lowering therapies could reduce the urate level in patients with CKD, but the benefit of such therapy in renal disease is still unclear. PROSPERO identifier: CRD42020222601.

Keywords: chronic kidney disease; hyperuricemia; network meta-analysis; urate-lowering therapy.

Publication types

  • Meta-Analysis

MeSH terms

  • Allopurinol / adverse effects
  • Bayes Theorem
  • Febuxostat / adverse effects
  • Gout Suppressants / adverse effects
  • Humans
  • Hyperuricemia* / drug therapy
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Treatment Outcome
  • Uric Acid

Substances

  • Gout Suppressants
  • Febuxostat
  • Uric Acid
  • Allopurinol