Whether urate-lowering agents protect the kidneys is still an open question. A new network meta-analysis of 16 randomized controlled trials including 1943 patients with chronic kidney disease (CKD) finds insufficient evidence to support renoprotection.

Febuxostat, allopurinol, and benzbromarone all significantly lowered urate levels compared with placebo. Febuxostat treatment also significantly reduced serum uric acid levels by a mean difference of 1.55 mg/dL compared with allopurinol, Wei Qin, MD, and colleagues from West China Hospital, Sichuan University in Chengdu, China reported in Frontiers of Pharmacology. Results were consistent in subgroup analyses restricted to patients with hyperuricemia and CKD or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2.

With respect to CKD progression, the 3 urate-lowering agents did not slow eGFR decline or reduce serum creatinine or proteinuria compared with placebo or each other in patients who had CKD with or without hyperuricemia, the investigators reported.

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Febuxostat was associated with a significant reduction in systolic blood pressure by a mean difference of 6.6 mm Hg compared with allopurinol in patients with an eGFR of less than 60 mL/min/1.73 m2 and hyperuricemia.

Inadequate dosing of allopurinol due to concerns over nephrotoxicity may have partly contributed to these results, the investigators suggested. They found no significant differences among agents in adverse event rates.

“There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia,” Dr Qin’s team concluded. Data from large, double-blind randomized controlled trials are needed.


Liu X, Qiu Y, Li D, Tan J, Liang X and Qin W. Effectiveness of drug treatments for lowering uric acid on renal function in patients with chronic kidney disease and hyperuricemia: a network meta-analysis of randomized controlled trials. Front. Pharmacol. 12:690557. doi:10.3389/fphar.2021.690557