One of the earliest indicators of kidney disease is new-onset albuminuria, which is predicted by an elevation in serum uric acid. Austin G. Stack, MBBCh, MD, MSc, FASN FRCP, and colleagues conducted a study designed to examine the effects of intensive lowering of uric acid on albuminuria by combining verinurad with febuxostat in patients with type 2 diabetes mellitus and albuminuria. Results of the study were reported during a presentation at Kidney Week 2019. The oral session presentation was titled Verinurad Plus Febuxostat Rapidly Reduces Albuminuria in Type 2 Diabetes Independent of Preexisting Kidney Disease.
The phase 2, parallel group, multicenter, randomized, double-blind, placebo-controlled trial included adults with type 2 diabetes, albuminuria, and hyperuricemia. Participants were randomized to verinurad 9 mg plus febuxostat 80 mg once daily, or placebo, and were followed for 24 weeks. The primary outcome of interest was a reduction in urinary albumin to creatinine ratio (UACR) at 12 weeks compared with baseline. Changes in UACR were calculated according to baseline characteristics, including UACR and estimated glomerular filtration rate (eGFR).
In the verinurad plus febuxostat group, baseline UACR was 459 mg/g (n=32), compared with 412 mg/g in the placebo group (n=28). In the verinurad plus febuxostat group, there was rapid and sustained improvement in UACR; the improvement met prespecified criteria for statistical significance. At weeks 1, 12, and 24, the reductions versus placebo were 39%, 39%, and 49% (week 12, 90% confidence interval, –62% to –4%; P=.0747). The reduction in UACR was consistent across subgroups, including those based on UACR and eGFR. Verinurad plus febuxostat was well tolerated.
In conclusion, the researchers said, “Intensive urate lowering with verinurad plus febuxostat significantly reduced UACR in patients with type 2 diabetes mellitus, albuminuria, and hyperuricemia. Reduction was rapid, sustained, and similar regardless of baseline eGFR and degree of albuminuria. A larger study is underway to determine which patient groups might benefit most from verinurad combination therapy.”
Source: Stack AG, Dronamraju N, Parkinson J, et al. Verinurad plus febuxostat rapidly reduces albuminuria in type 2 diabetes independent of preexisting kidney disease. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2019 (Abstract SA-OR086), November 9, 2019, Washington, DC.
Funding for this study was provided by AstraZeneca.