Kidney Protection Options in 2025: Are Renin-Angiotensin System Inhibitors Still Needed?

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.