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Kidney Protection Options in 2025: Are Renin-Angiotensin System Inhibitors Still Needed?
1Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.
Abstract:
The therapeutic advantage of angiotensin-converting enzyme inhibitors was first described more than 40 years ago by Brenner and colleagues. Since then, a number of clinical trials have demonstrated the utility of drugs that modify the renin-angiotensin system (RAS) to slow the rate of progression of kidney disease in patients with and without diabetes. However, despite the well-known benefits of these drugs in reducing cardiorenal events, most clinicians are not using them consistently in their practice. The lack of use is related to concerns about increases in serum creatinine and the development of hyperkalemia. With the advent of many newer drugs to delay the progression of kidney disease and reduce the likelihood of cardiovascular events which have lesser effects on increasing serum creatinine or potassium, clinicians may prefer to use these therapies. Although trials of the newer cardiorenal protective therapies were conducted on the background of RAS inhibition, only the highest tolerated dose of RAS inhibition was used, a dose not shown to provide cardiorenal protection in a clinical trial. As multimodal therapy for slowing the progression of chronic kidney disease and reducing cardiovascular events moves into prime time, one has to wonder whether RAS inhibition will remain a foundation therapy.
Insights
Angiotensin-converting enzyme inhibitors slow kidney disease progression, but many clinicians avoid them due to side effect concerns. Newer therapies may overshadow these established drugs in practice.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Angiotensin-converting enzyme (ACE) inhibitors, which modify the renin-angiotensin system (RAS), have demonstrated benefits in slowing kidney disease progression for over 40 years.
- Despite proven efficacy in reducing cardiorenal events, consistent clinical use of RAS inhibitors is suboptimal.
- Concerns regarding elevated serum creatinine and hyperkalemia limit the widespread adoption of these therapies.
Purpose of the Study:
- To evaluate the current role and future prospects of renin-angiotensin system (RAS) inhibition in the multimodal management of chronic kidney disease (CKD) and cardiovascular events.
- To address the clinical inertia surrounding RAS inhibitor use despite established benefits.
Main Methods:
- Review of clinical trial data and established literature on RAS inhibitors and newer cardiorenal protective therapies.
- Analysis of factors influencing clinical practice patterns regarding antihypertensive and cardiorenal protective medications.
Main Results:
- RAS inhibitors are effective in slowing CKD progression and reducing cardiorenal events.
- Clinician hesitancy stems from concerns about hyperkalemia and increased serum creatinine.
- Newer therapies with potentially fewer side effects are emerging as alternatives or adjuncts.
Conclusions:
- The optimal role of RAS inhibition in contemporary cardiorenal protection strategies requires re-evaluation.
- As multimodal therapies advance, the foundational status of RAS inhibition may be challenged.
- Further research and clinical guidance are needed to optimize the use of RAS inhibitors alongside newer agents.
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