Recent evidence on the effect of urate-lowering treatment on the progression of kidney disease

Purpose of review: Several observational studies have shown that hyperuricemia is associated with chronic kidney disease (CKD) progression and is a potential therapeutic target in people with CKD. This review discusses the results of three recently published placebo-controlled randomized trials evaluating the effect of urate-lowering treatment on the progression of CKD with at least 2 years of follow-up.

Recent findings: The Febuxostat versus Placebo Randomized Controlled Trial Regarding Reduced Renal Function in Patients with Hyperuricemia Complicated by Chronic Kidney Disease Stage 3 trial evaluated the effect of febuxostat in 443 patients with stage 3 CKD (mean estimated glomerular filtration rate [eGFR] 45 mL/min/1.73 m2) and asymptomatic hyperuricemia (mean serum urate 7.8 mg/dL). The Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase and Preventing Early Renal Loss in Diabetes trials respectively evaluated the effect of allopurinol in 369 adults with stage 3 or 4 CKD (mean eGFR 31.7 mL/min/1.73 m2, mean serum urate 8.2 mg/dL) with high progression risk and 530 patients with type 1 diabetes and diabetic kidney disease (mean eGFR 74.7 mL/min/1.73 m2, mean serum urate 6.1 mg/dL). Despite the large and sustained reductions in serum urate levels in all 3 trials, urate-lowering treatment with febuxostat or allopurinol did not result in clinically meaningful improvement in kidney outcomes.

Summary: The results of large and well-designed placebo-controlled trials do not support the use of urate-lowering therapy to slow the progression of CKD.