Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial

Abstract

Background: Hyperuricemia is a putative risk factor for the progression of chronic kidney disease (CKD). We hypothesized that control of asymptomatic hyperuricemia may slow disease progression in CKD.

Study design: This was a single-center, double-blind, randomized, parallel-group, placebo-controlled study.

Setting & participants: Eligible participants were adults from Eastern India aged 18 to 65 years with CKD stages 3 and 4, with asymptomatic hyperuricemia.

Intervention: The intervention group received febuxostat, 40mg, once daily for 6 months, while the placebo group received placebo; both groups were followed up for 6 months.

Outcomes: The primary outcome was the proportion of patients showing a >10% decline in estimated glomerular filtration rate (eGFR) from baseline in the febuxostat and placebo groups. Secondary outcomes included changes in eGFRs in the 2 groups from baseline and at the end of the study period.

Results: 45 patients in the febuxostat group and 48 in the placebo group were analyzed. Mean eGFR in the febuxostat group showed a nonsignificant increase from 31.5±13.6 (SD) to 34.7±18.1mL/min/1.73m(2) at 6 months. With placebo, mean eGFR decreased from a baseline of 32.6±11.6 to 28.2±11.5mL/min/1.73m(2) (P=0.003). The difference between groups was 6.5 (95% CI, 0.08-12.81) mL/min/1.73m(2) at 6 months (P=0.05). 17 of 45 (38%) participants in the febuxostat group had a >10% decline in eGFR over baseline compared with 26 of 48 (54%) from the placebo group (P<0.004).

Limitations: Limitations of this study included small numbers of patients and short follow-up, and ∼10% of the randomly assigned population dropped out prior to completion.

Conclusions: Febuxostat slowed the decline in eGFR in CKD stages 3 and 4 compared to placebo.

Keywords: Chronic kidney disease (CKD); disease progression; estimated glomerular filtration rate (eGFR); febuxostat; hyperuricemia; randomized controlled trial (RCT); renal function; uric acid; xanthine oxidase inhibitor.