Aldosterone synthase inhibition reduces albuminuria in CKD

An aldosterone synthase inhibitor, provisionally named BI 690517, reduced urine albumin to creatinine ratio (UACR) on its own and together with empagliflozin in chronic kidney disease (CKD).

Despite treatment with available therapies such as sodium-glucose cotransporter 2 (SGLT2) inhibitors like empagliflozin, people with CKD are at high risk for progression. Overproduction of aldosterone is known to accelerate CKD progression.

“This phase 2 clinical trial (NCT05182840) assessed the safety and efficacy of an aldosterone inhibitor, BI 690517, with or without empagliflozin in participants with CKD,” Prof. Katherine Tuttle (University of Washington, WA, USA) explained [1]. The trial included 714 patients with CKD; approximately 70% had type 2 diabetes. They were first randomised to 10 mg empagliflozin (n=356) or placebo (n=358). After 8 weeks, each group was subdivided into 3 groups receiving BI 690517 (3 mg, 10 mg, or 20 mg), or a placebo. The second leg lasted 14 weeks. The primary endpoint was a change in UACR in the last 14 weeks. Secondary endpoints included the proportion of patients with ≥30% or ≥15% change in UACR and changes in estimated glomerular flow rate (eGFR). Baseline characteristics were similar across all groups.

Participants with and without empagliflozin had a decrease in UACR with BI 690517, with the 10 mg and 20 mg BI 690517 dosages resulting in similar effects. The highest percentage of patients with UACR reduced ≥30% was in the 10 mg BI 690517 plus empagliflozin group, where 70% of the patients met that endpoint. There were no unexpected adverse events. BI 690517 will be further tested in the EASi-KIDNEY phase 3 clinical trial that will begin recruiting in 2024.

1. Tuttle KR, et al. Aldosterone Synthase Inhibition with or Without Background Sodium Glucose Cotransporter 2 Inhibition in CKD: A Phase II Clinical Trial. FR-OR111, ASN Kidney Week 2023, 2–5 November, Philadelphia, PA, USA.

 

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Posted on 28 November, 202331 January, 2024