Beyond Hypertension: Lorundrostat’s Potential to Protect Kidney Function, with Matthew Weir, MD

Lorundrostat reduced automated office systolic blood pressure (AOSBP) and albuminuria in people with chronic kidney disease (CKD) with concurrent uncontrolled hypertension (uHTN) who were receiving SGLT2.

These findings, from the phase 2 Explore-CKD trial, were presented by Matthew Weir, MD, Professor of Medicine at the University of Maryland School of Medicine at the American Society of Nephrology (ASN) Kidney Week 2025, held November 5-9, 2025, in Houston, Texas.

Lorundrostat is a next-generation aldosterone synthase inhibitor (ASI) which is emerging as a promising solution for a long-implicated target for lowering blood pressure while offering potential kidney protection.

Weir and colleagues evaluated lorundrostat in patients with uncontrolled hypertension (uHTN), CKD, and albuminuria already on standard-of-care therapy, including ACE inhibitors or ARBs and SGLT2 inhibitors. The randomized, double-blind, placebo-controlled crossover study enrolled 59 adults with a mean eGFR of 43 mL/min/1.73m² and baseline systolic blood pressure of 149 mmHg.

Investigators noted that lorundrostat achieved a placebo-adjusted reduction of 7.5 mmHg (90% CI, -11.6 to -3.4, P = .0024) in systolic blood pressure and a 25.6% drop (90% CI, -35.8 to -13.7, P = .0015) in albuminuria, indicating both meaningful hemodynamic and renal benefits. Importantly, these effects were seen on top of existing renin–angiotensin and SGLT2 inhibition, demonstrating a strong additive effect in a population often difficult to treat. Adverse events were few, with mild hyperkalemia in only a small subset of participants and modest, expected changes in eGFR.

HCPLive spoke with Weir during the meeting to learn more about the importance of the new data. HE emphasized lorundrostat’s dual potential for uHTN and CKD.

"All in all, it was a very successful clinical trial, and obviously a pilot for much larger prospective, randomized, controlled trials to be done in the future. So I think there's great potential for this class of medications, moving forward for people with resistant HTN, CKD, and albuminuria as a potential of protective therapy for kidney function," Weir said.

Relevant disclosures for Weir include Merck, Boehringer Ingelheim, AztraZeneca, Relypsa, Vifor, Boston Scientific, AbbVie, Janssen, Bayer, and Reata.

Reference

Weir WM, Bhaduri S, Lee K, et al. Lorundrostat, a Novel Aldosterone Synthase Inhibitor (ASI), in Participants with Uncontrolled Hypertension, CKD, and Albuminuria: Results from Explore-CKD. Presented at: ASN Kidney Week. Houston, Texas. November 05-09, 2025. #FR-OR091