Reno-protective effects of xanthine oxidase inhibitors in patients with type 2 diabetes and chronic kidney disease: a systematic review and meta-analysis

Background: The effect of lowering uric acid levels on renal function in patients with diabetic kidney disease remains unclear. Previous randomized controlled trials (RCTs) have reported conflicting results regarding the effects of xanthine oxidase inhibitors on renal function. This study aimed to examine the renoprotective effects of xanthine oxidase inhibitors (febuxostat and topiroxostat) in patients with diabetic kidney disease. Methods: Relevant RCTs were searched using PubMed, Embase, and Cochrane Central databases. Ultimately, five RCTs were included in the meta-analysis. The assessed renal endpoints included changes in the estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio. The meta-analysis was conducted using Review Manager version 5.4. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for changes in renal endpoints between the groups after the study period. A subgroup analysis was conducted based on the type of intervention, results of the risk of bias assessment, and baseline renal function. Results: Although the use of febuxostat or topiroxostat did not induce a significant change in eGFR compared with the placebo, it showed a tendency to delay renal function decline (SMD = 0.32, 95% CI = [− 0.00; 0.64]). There was no significant difference in albuminuria between the two groups (SMD = 0.26, 95% CI = [− 0.10; 0.62]). Conclusions: This study suggests the potential of febuxostat or topiroxostat to delay renal function decline in patients with diabetes and underlying renal impairment, that needs to be confirmed in further studies. Trial registration: INPLASY registration number 202450024.