Impact of Urate-Lowering Agents on Renal Outcomes in Chronic Kidney Disease: A Systematic Review

Chronic kidney disease (CKD) poses a significant global health burden, with hyperuricemia emerging as a potential modifiable risk factor for disease progression. Urate-lowering agents (ULAs) have been hypothesized to preserve renal function by reducing serum uric acid (SUA) levels and mitigating associated pathogenic mechanisms. However, clinical evidence regarding their efficacy remains inconsistent. This systematic review aimed to evaluate the effects of ULAs on renal outcomes in CKD patients by synthesizing evidence from recent placebo-controlled randomized trials. A comprehensive search of PubMed, Scopus, Web of Science, Embase, and ClinicalTrials.gov was conducted to identify randomized controlled trials (RCTs) published between 2020 and 2025. Ten studies met the inclusion criteria, assessing allopurinol, febuxostat, verinurad, and topiroxostat. The risk of bias was evaluated using the Cochrane Risk of Bias 2 (ROB 2) tool (London, United Kingdom). Data were synthesized narratively due to clinical and methodological heterogeneity. Febuxostat demonstrated potential renal benefits, with significant estimated glomerular filtration rate (eGFR) preservation in three studies. Allopurinol showed neutral effects on eGFR decline in large trials. Albuminuria reduction was observed with verinurad plus febuxostat but not with other ULAs. Safety profiles were favorable across studies, with no significant differences in adverse events versus placebo. While febuxostat may slow CKD progression in select populations, evidence for allopurinol and combination therapies remains inconclusive. Heterogeneity in outcomes underscores the need for personalized treatment and further research to identify optimal candidates for ULA therapy.