Comparison of the Effectiveness and Safety of Allopurinol and Febuxostat Use in CKD Patients with Hyperuricemia: A Systematic Review

Background: Hyperuricemia is common in patients with Chronic Kidney Disease (CKD) and may accelerate renal function decline and increase cardiovascular risk. Allopurinol and febuxostat are xanthine oxidase inhibitors, but their comparative efficacy and safety remain inconsistent.Objective: To compare the effectiveness and safety of allopurinol and febuxostat in patients with CKD and hyperuricemia. Methods: This systematic review was conducted according to the PRISMA 2020 guidelines and prospectively registered. A literature search was performed in the PubMed, ScienceDirect, and Google Scholar databases for articles published between 2021 and 2025. The quality assessment (risk of bias) was conducted using the JBI Critical Appraisal Tools and the Newcastle-Ottawa Scale (NOS). The inclusion criteria comprised comparative clinical studies (RCTs and cohort studies) comparing allopurinol and febuxostat in patients with CKD stages 3–5. Results: Of the 50 articles identified, following rigorous PRISMA screening, 8 original articles met the inclusion criteria and were analyzed, excluding non-comparative and animal studies. The majority of studies showed that febuxostat resulted in a greater reduction in serum uric acid levels, as well as improvements in estimated glomerular filtration rate (eGFR) and serum creatinine parameters. In contrast, large-scale cohort studies reported that allopurinol was more consistent in slowing CKD progression and demonstrated more favorable cardiovascular outcomes in certain populations. The risk-of-bias assessment confirmed that the methodological quality of the included studies ranged from moderate to high. Conclusion: Febuxostat appears to be superior in reducing serum uric acid levels, whereas allopurinol demonstrates greater consistency in renal protection and cardiovascular outcomes in long-term cohort studies. The choice of therapy should be individualized based on CKD stage, cardiovascular risk profile, comorbidities, and safety considerations.