Urate-lowering therapy involving allopurinol or febuxostat may reduce the risk for renal events in patients with asymptomatic hyperuricemia, according to new research.

Investigators performed a systematic review of 23 randomized controlled trials involving 3209 patients receiving 8 urate-lowering therapies. In a network meta-analysis of trials comparing allopurinol, febuxostat, or rasburicase with placebo or no urate-lowering therapy, allopurinol and febuxostat significantly reduced the risk of composite renal events by 61% and 32%, respectively, Pawin Numthavaj, PhD, of Ramathibodi Hospital, Mahidol University in Bangkok, Thailand, and colleagues reported in BMC Nephrology. Composite renal events included renal function decline, end-stage kidney disease, and initiation of renal replacement therapy, but excluded isolated albuminuria. Compared with placebo or no therapy, allopurinol and febuxostat treatment were significantly associated with a higher estimated glomerular filtration rate (eGFR): mean difference of 3.69 and 2.89 mL/min/1.73 m2, respectively.

The investigators found no significant reductions in the composite risk for major adverse cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization, using urate-lowering therapy for asymptomatic hyperuricemia.

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Adverse event rates did not differ significantly between groups receiving allopurinol or febuxostat vs placebo or no therapy. The investigators could not assess severe allopurinol hypersensitivity.

According to Dr Numthavaj’s team, “evidence suggests that allopurinol and febuxostat are [urate-lowering therapies] that offer the greatest potential benefit to minimize composite renal events and improve renal function without significant risk of increased [adverse events].” They encouraged future large, long-term trials comparing multiple urate-lowering therapies in this population.


Sapankaew T, Thadanipon K, Ruenroengbun N, et al. Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials. BMC Nephrol. Published online June 23, 2022. doi:10.1186/s12882-022-02850-3