RAAS blockade in the kidney Life-Cycle - Treatment Standard

The renin–angiotensin–aldosterone system (RAAS) plays a central role in regulating renal hemodynamics, sodium and water balance, and cardiovascular homeostasis. Chronic RAAS activation contributes to hypertension, proteinuria, inflammation, fluid overload, and fibrosis, making RAAS blockade (RAASb) a cornerstone therapy across the kidney life cycle. Over the past decades, ACE inhibitors, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor antagonists have demonstrated substantial benefits in slowing chronic kidney disease (CKD) progression, reducing proteinuria, and lowering cardiovascular risk. However, the efficacy and safety of RAASb vary according to the kidney life cycle. Evidence supports its use in proteinuric CKD and even in advanced stages, whereas the benefit in non-proteinuric disease remains limited. Novel non-steroidal mineralocorticoid receptor antagonists such as finerenone further enhance renal and cardiovascular protection, particularly in persons with diabetes and CKD. In dialysis populations, RAASb may preserve residual kidney function improve cardiac structure/function, although the benefit of steroidal MRAs remains uncertain. In kidney transplantation, RAASb appears safe and may improve long-term graft and patient survival, particularly when initiated early. The emergence of SGLT2 inhibitors and GLP-1 receptor agonists has reshaped therapeutic strategies, with accumulating evidence supporting complementary rather than competing roles with RAASb. This review synthesizes current evidence on RAAS modulation across the kidney life cycle from primary prevention to advanced CKD, dialysis, and transplantation, highlighting both established benefits and areas of current clinical uncertainty.