Impact of urate-lowering therapy on the course of chronic kidney disease in patients with asymptomatic hyperuricemia: a meta-analysis of randomized controlled trials

Abstract

The presented study has been carried out to identify the effect of urate-lowering therapy with xanthine oxidase inhibitors on glomerular filtration rate and serum uric acid in patients with asymptomatic hyperuricemia and chronic kidney disease. A systematic review of randomized controlled trials has been conducted; its results based on meta-analysis has been evaluated. A systematic search and selection of publications in Embase, PubMed, Cochrane Library, and eLibrary databases has been performed. The studied drugs were xanthine oxidase inhibitors: allopurinol and febuxostat. The study considered the following parameters such as efficacy endpoints, namely, glomerular filtration rate and serum uric acid after 3–15 months of follow-up. Clinical and methodological heterogeneity of the included randomized controlled trials has been assessed as well as publication bias and risk of systematic error. Synthesis has been performed using bivariate meta-analysis assessing residual statistical heterogeneity. 7 selected randomized controlled trials (1203 patients) have been included in the meta-analysis. This analysis revealed that medication urate-lowering therapy (allopurinol or febuxostat) was associated with higher glomerular filtration rate (+3.0 ml/min/1.73 m2; 95% confidence interval +0.4 to +5.6; p = 0.022) compared with the controls (placebo/no urate-lowering therapy) at 3–15 months of follow-up. Along with this, medication urate-lowering therapy (allopurinol or febuxostat) has been found to result in lower serum uric acid (−3.3 mg/dl; 95% confidence interval −3.8 to −2.8; р 0.001) compared to the controls (placebo / no urate-lowering therapy) at 3–15 months of follow-up. The results of the meta-analysis have demonstrated a positive role of allopurinol and febuxostat in increasing glomerular filtration rate and decreasing serum uric acid in patients with chronic kidney disease and asymptomatic hyperuricemia. The presented data suggest that therapeutic measures aimed at the elimination of asymptomatic hyperuricemia, including the use of xanthine oxidase inhibitors, may be important in slowing the progression of chronic kidney failure and may be additional factors of nephroprotection.