Does uric acid-lowering treatment slow the progression of chronic kidney disease? A meta-analysis of randomized controlled trials

Introduction: Hyperuricemia has been proposed as an independent factor in the development and progression of chronic kidney disease (CKD). However, the effect of uric acid-lowering therapies on delaying CKD progression is still uncertain. Therefore, this systemic review aims to assess the effect of uric acid-lowering therapies on renal outcomes in pre-dialysis CKD patients.

Methods: PubMed, Cochrane Library, and Lilacs databases were searched until April 24, 2021, for randomized clinical trials of CKD patients on uric acid-lowering treatment with xanthine-oxidase (XO) inhibitors. The weighted mean difference (WMD) or standard mean difference (SMD) with confidence interval (CI) were pooled using a random-effects model.

Results: Among 567 studies found, eighteen met the inclusion criteria (n=2463 participants). Compared to the patient's control group, the WMD for the glomerular filtration ratio (GFR) and serum creatinine changes of the treated group was 2.02ml/min/1.73m² (95%CI 0.41 to 3.63, P=0.014) and -0.19mg/dl (95%CI -0.34 to -0.04, I²=86.2%, P=0.011), respectively. Subgroup analyses showed that the difference in follow-up time and CKD population type in the studies may explain the controversy about the role of uric acid-lowering therapies in CKD progression. The GFR and creatinine outcomes analysis by types of XO inhibitors showed no difference between the control and treated groups. Uric acid-lowering therapies were strongly associated with decreased serum uric acid and urinary protein-creatinine ratio and urinary albumin-creatinine ratio.

Conclusions: These findings suggest that uric acid-lowering treatment may slow CKD progress and reduce protein and albumin excretion. However, larger and properly powered randomized clinical trials with specific CKD populations are needed to confirm these findings.