Incidence and risk of nephrolithiasis with uricosuric therapies for the treatment of gout: a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Abstract

To assess the incidence and risk of nephrolithiasis in people receiving uricosuric therapies for gout. A search was conducted using MEDLINE, Embase, Cochrane Library, Web of Science and Clinical Trials.gov electronic databases on 16 May 2023 (updated 10 May 2024). Randomized controlled trials (RCTs) and cohort studies assessing the incidence and/or risk of nephrolithiasis in adults with gout treated with uricosuric therapies were included (with or without a non-uricosuric urate-lowering therapy [ULT] comparator group). Other designs and studies involving people with asymptomatic hyperuricaemia only were excluded. A random-effects model was used to calculate pooled incidence and risk estimates. Risk of bias assessments were performed for all included studies. Twenty-three studies (10 RCTs, 13 cohort studies) were included in the meta-analysis (n = 78 042 participants, 15 385 received a uricosuric). The pooled incidence of nephrolithiasis amongst participants taking uricosuric therapies was 3.35% (95% CI 2.03-4.92) (Benzbromarone [10 studies] 3.92% [1.89-6.52], Lesinurad [6 studies] 3.08% [1.38-5.38]). Pooled incidence by study design was 2.87% (95% CI 1.30-4.93) in 10 RCTs and 3.93% (1.95-6.44) in 13 cohort studies. The pooled risk ratio for nephrolithiasis in participants taking uricosuric therapies vs participants not taking a uricosuric (other ULT and/or placebo) (nine studies) was 1.63 (95% CI 1.33-2.00, P = 0.001). Nephrolithiasis is a common side effect of uricosuric therapies, although the quality of evidence for this is low-moderate due to significant heterogeneity and bias. Further research is required to identify those at highest risk, and who may benefit from additional interventions such as urinary alkalinization. Our estimates of incidence of nephrolithiasis and associated risk can lead to more informed shared treatment decisions in the management of gout.