Verinurad And Febuxostat Protect Kidney Function In T2D: Stu
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Hyperuricemia has been implicated in the development and progression of chronic kidney disease (CKD). Verinurad is a novel, potent, specific urate reabsorption inhibitor. Researchers evaluated the effects of intensive urate-lowering therapy with verinurad combined with the xanthine oxidase (XO) inhibitor febuxostat on albuminuria in patients with hyperuricemia and type 2 diabetes mellitus (T2DM).

This was a Phase 2, multicenter, prospective, randomized, double-blind, parallel-group, placebo-controlled trial. Patients aged more than 18 years with hyperuricemia, albuminuria, and T2DM were assessed. Patients were randomized 1:1 to verinurad (9 mg) and febuxostat (80 mg) or matched placebo once daily for 24 weeks.

The primary endpoint was change in urine albumin-to-creatinine ratio (UACR) from baseline after 12 weeks’ treatment. Secondary endpoints included safety and tolerability, and effect on kidney function.

-- In total, 60 patients were enrolled (n=32, verinurad and febuxostat; n=28, placebo).

-- UACRs after treatment with verinurad and febuxostat were lower than after placebo at 1, 12, and 24 weeks: -38.6%, -39.4% and -49.3%, respectively.

-- Serum urate (sUA) levels after treatment with verinurad and febuxostat were 59.6% and 63.7% lower than after placebo at 12 and 24 weeks, respectively.

-- No clinically meaningful changes were observed in estimated glomerular filtration rates (eGFR), serum creatinine, or serum cystatin C concentrations.

-- Verinurad and febuxostat were well tolerated.

Few limitations of the study were: Sample size and study duration were insufficient to evaluate definitive effects of verinurad and febuxostat on UACR and kidney function. Generalizability was limited by exclusion of patients with stage 4 and 5 CKD.

Conclusively, Verinurad and febuxostat reduced albuminuria and lowered sUA concentrations in patients with T2DM, albuminuria, and hyperuricemia. Definitive assessment of their combined impact on preservation of kidney function awaits larger clinical studies.