Matthew R. Weir, MD is an attending physician and Director of the Division of Nephrology in the Department of Medicine at the University of Maryland Hospital.

Matthew Weir, MD

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, 

= .0024) in systolic blood pressure and a 25.6% drop (90% CI, -35.8 to -13.7, 

.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.

 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.

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

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Weir pointed out that significant benefits were seen with concurrent SGLT2 inhibitor use.

Debating the Usefulness of ACE/ARBs in Kidney & Cardiovascular Disease with Matthew Weir, MD

 in Philadelphia, PA, Matthew Weir, MD, professor and director of the division of nephrology at the University of Maryland School of Medicine, presented his analysis of the role that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) can still play in the modern 

According to the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 guidelines, ACE inhibitors or ARBs are strongly recommended for patients with chronic kidney disease (CKD). Additionally, ACE inhibitors are strongly encouraged for patients with moderate-to-severe albuminuria with diabetes and those with CKD and increased albuminuria regardless of diabetes status.

Cardiorenal protective measures have always involved multiple drugs, typically including some form of generic angiotensin blocker such as ACE/ARBs. However, these drugs are being prescribed less and less often as more current medications are pushed to the forefront, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and mineralocorticoid receptor agonists (MRAs).

Weir posits that changes in serum creatinine and serum potassium lead clinicians to avoid ACE/ARB medications, especially in guideline-based doses. However, Weir also makes the point that the medical field has had the means to combat these changes for some time.

“I don’t disagree that there are going to be subtle changes in serum potassium and serum creatinine, but we also know how to medically manage those, and we know how to look for other factors that may be causing these problems to occur,” Weir told 

. “So, from that standpoint, clinicians should be aware of some of the interactions with other medicines we’re using so as to avoid some of the pitfalls of using an ACE or an ARB appropriately in clinical practice.”

Additionally, despite their history of efficacy and safety in treating diabetic kidney disease and heart failure, Weir indicates that significant numbers of patients with either disease are not receiving these medications.

“The fact of the matter is, if you look at published data in the US of people with established diabetic kidney disease, less than half are receiving these drugs,” Weir said. “And of those, less than half are receiving them in doses that have been defined to be kidney protective in clinical trials.”

Additionally, Weir’s presentation indicated that lower doses of ACE/ARB have never been shown to be effective in slowing kidney disease progression. Traditionally, the highest tolerated doses have been consistently recommended in preventing mortality and morbidity in cardiovascular diseases, as well as for patients with diabetes, hypertension, CKD, and albuminuria.

Weir also acknowledged the possibility that, with newer medications showing the same or better treatment outcomes, ACE and ARBs may be overcomplicating treatment.

“In all of the trials with these drugs showing benefit, the patients have been receiving the highest tolerated dose of an ACE or an ARB, which in the real world is probably less or none,” Weir said. “And so more likely than not, these drugs are going to be every bit as effective with or without an ACE or an ARB. So, in a sense, the ACE and the ARB, as important as they are, maybe in a sense are cluttering the medication list.”

To that end, Weir poses the question of whether ACE/ARBs are necessary in the face of modern treatments such as MRA, which are very effective in anti-atherosclerotic heart failure and kidney disease.

“So, one of the questions I would ask is, would we be able to use MRA more effectively without the background of an ACE or an ARB, even in low dose, in our patients?” Weir said. “Because I suspect they may be a lot more effective in dealing with some of the forms of high blood pressure that we see, the proteinuria that we see in patients with chronic kidney disease.”

Weir makes the following disclosures: AstraZeneca, Bayer, Corcept, CSL Vifor, Boehringer-Ingelheim, NovoNordisk, Mineralys, Vera

Weir M. Do ACEI/ARB still have a role in the era of SGLT2i, MRA and GLP-1RA? Presented at the 9

 Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.

Stevens PE, Ahmed SB, Carrero JJ, et al. KDIGO 2024 clinical practice guideline for the Evaluation and management of chronic kidney disease. Kidney International. 2024;105(4). doi:10.1016/j.kint.2023.10.018

With so many new medications ostensibly filling the niche typically occupied by ACE/ARBs, are the medications practically useful in a changed treatment landscape?

Matthew Weir, MD: Prioritizing Cardiovascular Risk in Chronic Kidney Disease

22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC)

, Matthew Weir, MD, an attending physician and director of the division of nephrology in the department of medicine at the University of Maryland, emphasized the critical need for clinicians to prioritize cardiovascular risk management in patients with 

Highlighting that most CKD patients succumb to cardiovascular disease rather than kidney failure, Weir focused on the importance of early detection through estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) screening. This enables earlier intervention targeting hypertension, dyslipidemia, and diabetes, with goals such as blood pressure <130/80 mmHg, HbA1c <7%, and LDL cholesterol <55 mg/dL. He also underscored the necessity of comprehensive cardiovascular risk reduction over solely delaying CKD progression.

Looking to the future, Weir highlighted the transformative role of new therapies in cardio-renal disease management, including SGLT2 inhibitors, GLP-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists. These agents, used alongside traditional renin-angiotensin system blockers, represent a multimodal strategy to mitigate both cardiovascular events and CKD progression. Additionally, he noted the meeting’s focus on the interplay of dysmetabolism, inflammation, and their impact on vascular and organ health, with emerging insights into sleep, diet, exercise, and novel therapeutics offering exciting avenues for improving outcomes.

Weir concluded with a call to action for clinicians to integrate these advanced therapies into practice while maintaining a proactive, multidisciplinary approach to CKD care. This paradigm shift aims to address systemic risks and comprehensively improve long-term patient health.

Disclosures: Relevant disclosures for Weir include AstraZeneca, Bayer, Boehringer-Ingelheim, Johnson & Johnson, NovoNordisk, and others.

Weir M. Chronic Kidney Disease: Should We Worry about the Heart or Progression to ESKD. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Chronic kidney disease (CKD) patients face a higher risk of cardiovascular disease than kidney failure, necessitating a focus on cardiovascular risk management. Early detection through eGFR and UACR screening allows for timely intervention targeting hypertension, dyslipidemia, and diabetes. New therapies, including SGLT2 inhibitors and GLP-1 receptor agonists, offer a multimodal approach to managing cardio-renal disease. Emphasizing a comprehensive strategy, clinicians are encouraged to integrate these therapies and adopt a multidisciplinary approach to CKD care, addressing systemic risks and improving long-term patient outcomes.

Matthew Weir, MD discusses how a multidisciplinary approach is reshaping CKD management, with a focus on mitigating cardiovascular events.

Matthew Weir, MD

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