Aldosterone synthase inhibition for treatment of people with chronic kidney disease
13 affiliations
- 1Providence Medical Research Centre, Providence Inland Northwest Health, Spokane, WA, USA.
- 2Nephrology Division and Kidney Research Institute, University of Washington School of Medicine, Seattle, WA, USA.
- 3Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
- 4Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
- 5Department of Nephrology and Haemodialysis, University Hospital Centre "Dr Dragisa Misovic", Belgrade, Serbia.
- 6Department of Endocrinology and Metabolism, Cleveland Clinic Foundation, Cleveland, OH, USA.
- 7Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA.
- 8Toronto General Hospital, Toronto, ON, Canada.
- 9Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
- 10Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- 11Oxford Kidney Unit, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
- 12Division of Nephrology and St. Paul's Hospital/Providence Health care, University of British Columbia, Vancouver, Canada.
- 13Steno Diabetes Center, Copenhagen, Herlev, Denmark.
Abstract
Aldosterone contributes to the progression of chronic kidney disease (CKD) not only through its effects on blood pressure (BP) but also by promoting inflammation and fibrosis in the kidney and cardiovascular system. Despite contemporary treatment with renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, residual risk persists for adverse kidney and cardiovascular outcomes. Aldosterone synthase inhibition (ASI) has emerged as a potent strategy to directly suppress aldosterone production. Several selective inhibitors, including baxdrostat, lorundrostat, and vicadrostat, have been shown to lower aldosterone levels without affecting cortisol synthesis in a clinically meaningful manner. Clinical studies in hypertension consistently show a decrease in systolic BP with these agents. In a CKD population, vicadrostat dose-dependently reduced the urinary albumin-to-creatinine ratio with additional BP lowering, and possibly greater albuminuria reduction when combined with empagliflozin. Similar findings have been observed with lorundrostat and baxdrostat in patients with CKD and uncontrolled hypertension. Median increases in serum potassium of ∼0.3 mmol/l that have been observed with ASI were generally manageable in clinical trial populations. Emerging evidence from clinical trials and meta-analyses suggests that concomitant SGLT2 inhibitor therapy may mitigate the risk of clinically significant hyperkalaemia, also supporting the use of combination therapy. Overall, ASI provide a potentially beneficial approach to reduce residual risks of CKD. Several phase 3 trials testing vicadrostat or baxdrostat across different populations with CKD, hypertension, or cardiovascular disease will determine whether favourable effects on albuminuria translate into improved kidney and cardiovascular outcomes.
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BibTeX
@article{tuttle2026aldosterone,
title = {{Aldosterone synthase inhibition for treatment of people with chronic kidney disease}},
author = {Katherine R Tuttle and Jasna B Trbojevic-Stankovic and Radica Z Alicic and Maria Luiza Caramori and David Cherney and Ricardo Correa Rotter and William G Herrington and Parminder K Judge and Adeera Levin and Peter Rossing},
journal = {Clinical kidney journal},
year = {2026},
month = jul,
doi = {10.1093/ckj/sfag229},
url = {https://europepmc.org/article/PMC/PMC13716676},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Aldosterone synthase inhibition for treatment of people with chronic kidney disease
AU - Katherine R Tuttle
AU - Jasna B Trbojevic-Stankovic
AU - Radica Z Alicic
AU - Maria Luiza Caramori
AU - David Cherney
AU - Ricardo Correa Rotter
AU - William G Herrington
AU - Parminder K Judge
AU - Adeera Levin
AU - Peter Rossing
PY - 2026
DA - 2026/07/10
JO - Clinical kidney journal
DO - 10.1093/ckj/sfag229
UR - https://europepmc.org/article/PMC/PMC13716676
AB - Aldosterone contributes to the progression of chronic kidney disease (CKD) not only through its effects on blood pressure (BP) but also by promoting inflammation and fibrosis in the kidney and cardiovascular system. Despite contemporary treatment with renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, residual risk persists for adverse kidney and cardiovascular outcomes. Aldosterone synthase inhibition (ASI) has emerged as a potent strategy to directly suppress aldosterone production. Several selective inhibitors, including baxdrostat, lorundrostat, and vicadrostat, have been shown to lower aldosterone levels without affecting cortisol synthesis in a clinically meaningful manner. Clinical studies in hypertension consistently show a decrease in systolic BP with these agents. In a CKD population, vicadrostat dose-dependently reduced the urinary albumin-to-creatinine ratio with additional BP lowering, and possibly greater albuminuria reduction when combined with empagliflozin. Similar findings have been observed with lorundrostat and baxdrostat in patients with CKD and uncontrolled hypertension. Median increases in serum potassium of ∼0.3 mmol/l that have been observed with ASI were generally manageable in clinical trial populations. Emerging evidence from clinical trials and meta-analyses suggests that concomitant SGLT2 inhibitor therapy may mitigate the risk of clinically significant hyperkalaemia, also supporting the use of combination therapy. Overall, ASI provide a potentially beneficial approach to reduce residual risks of CKD. Several phase 3 trials testing vicadrostat or baxdrostat across different populations with CKD, hypertension, or cardiovascular disease will determine whether favourable effects on albuminuria translate into improved kidney and cardiovascular outcomes.
SN - 2048-8505
SN - 2048-8513
ER -