Intensive Urate-Lowering May Protect Kidneys in Type 2 Diabetes

In a study of patients with type 2 diabetes, verinurad combined with febuxostat led to a 39% reduction in UACR compared with placebo after 12 weeks of treatment, the primary endpoint.

Intensive serum urate-lowering with a combination of verinurad, a novel urate transporter 1 (URAT1) inhibitor, and febuxostat may provide greater kidney protection than usual therapy.

In a phase 2 trial, investigators randomly assigned 60 patients with type 2 diabetes, hyperuricemia (serum uric acid of 6.0 mg/dL or higher), and albuminuria (urinary albumin-to-creatinine ratio [UACR] of 30–3500 mg/g) to verinurad (9 mg) and the xanthine oxidase inhibitor febuxostat (80 mg) once daily (32 patients) or placebo (28 patients) for 24 weeks. Patients were required to have a baseline estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m² or higher and to be taking a stable dose of a renin-angiotensin-system inhibitor, if tolerated.

Serum urate levels declined 59.6% and 63.7% more at 12 and 24 weeks, respectively, with verinurad plus febuxostat compared with placebo, Austin G. Stack, MD, of the University of Limerick in Limerick, Ireland, and colleagues reported in the American Journal of Kidney Diseases. Further, UACR declined by 38.6%, 39.4%, and 49.3% more at 1, 12, and 24 weeks, respectively, with the intensive urate-lowering therapy compared with placebo.

No clinically meaningful changes were observed in eGFR, serum creatinine, or serum cystatin C. Larger and longer clinical trials are needed to definitively assess whether combining the urate-lowering therapies preserves kidney function, according to the investigators.

Verinurad and febuxostat were well tolerated. Nausea, diarrhea (12.5% vs 3.6% placebo), and dizziness (9.4% vs 0%) were the most common adverse events.

“The observed effects of this treatment were independent of blood pressure,” Dr Stack’s team noted. “This novel approach might confer additional benefits to patients with T2DM beyond the use of existing renoprotective strategies.”

Disclosure: This clinical trial was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.

Reference

Stack AG, Dronamraju N, Parkinson J, et al. Effect of intensive urate-lowering with combined verinurad and febuxostat on albuminuria in patients with type 2 diabetes: a randomized trial. Am J Kidney Dis. doi:10.1053/j.ajkd.2020.09.009