Photo Credit: Mohammed Haneefa Nizamudeen
The following is a summary of “Combination Treatment with Verinurad and Allopurinol in CKD: A Randomized Placebo and Active Controlled Trial,” published in the February 2024 issue of Nephrology by Heerspink et al.
Researchers conducted a phase 2b retrospective study to investigate the potential nephroprotective effects of the urate transporter 1 inhibitor verinurad, combined with the xanthine oxidase inhibitor allopurinol, on reducing albuminuria in patients with chronic kidney disease (CKD) and hyperuricemia.
They assessed a randomized, placebo, and active-controlled trial, recruiting participants with serum urate concentrations ≥6.0 mg/dL, estimated glomerular filtration rate (eGFR) ≥25 mL/minute/1.73 m2, and a urinary albumin-to-creatinine ratio (UACR) 30-5000 mg/g into one of five treatment arms as; placebo, placebo + allopurinol 300 mg/day, verinurad 3 mg + allopurinol 300 mg/day, verinurad 7.5 mg + allopurinol 300 mg/day, or verinurad 12 mg + allopurinol 300 mg/day in a 1:1:1:1:1 ratio. The primary outcome measure was the alteration in UACR from baseline to 34 weeks. Secondary outcome measures included changes from baseline in UACR at week 60 and alterations in serum urate and eGFR at weeks 34 and 60.
The results showed that 861 adults (August 2019- November 2021) with CKD (mean age 65 years, 33.0% female, mean eGFR 48 mL/min/1.73m2, median UACR 217 mg/g) were enrolled. At 34 weeks, the geometric mean percentage change in UACR from baseline did not differ among treatment groups: (16.7% [95% CI -0.6, 37.1] in the 3 mg group, 15.0% [95%CI -1.85, 34.6] in the 7.5 mg group, 14.0% [95%CI -3.4, 34.4] in the 12 mg group, compared to 9.9% [95%CI -6.6, 29.4] in the allopurinol group and 37.3% [95%CI 16.6, 61.8] in the placebo group). UACR and eGFR change from baseline did not differ among treatment groups after 60 weeks. The verinurad/allopurinol combination dose-dependently reduced serum urate concentrations compared to placebo. The proportion of patients with AEs and serious adverse events was balanced among treatment groups.
Investigators concluded that combining verinurad with allopurinol lowered serum urate but did not improve kidney function (UACR and eGFR) compared to allopurinol alone or placebo.
Source: journals.lww.com/jasn/abstract/9900/combination_treatment_with_verinurad_and.262.aspx