A Comprehensive Review on the Role of Renin Angiotensin Aldosterone System Blockade in Chronic Kidney Disease

Chronic kidney disease (CKD) is a growing global health burden associated with substantial morbidity, mortality, and progression to end-stage renal disease (ESRD). Activation of the renin angiotensin aldosterone system (RAAS) plays a central role in the pathogenesis and progression of CKD by promoting intraglomerular hypertension, proteinuria, inflammation, oxidative stress, and renal fibrosis. These mechanisms provide a strong rationale for RAAS inhibition as a cornerstone of renoprotective therapy. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been extensively studied in both diabetic and non-diabetic CKD. Beyond effective blood pressure control, these agents reduce proteinuria, preserve glomerular structure, and slow the decline in glomerular filtration rate. Landmark clinical trials have demonstrated that reductions in albuminuria strongly correlate with improved renal outcomes, establishing proteinuria as both a marker and mediator of CKD progression. Consequently, current clinical guidelines recommend ACEIs or ARBs as first-line therapy in patients with proteinuria CKD. Dual RAAS blockade with combined ACEI and ARB therapy has been proposed to achieve more complete RAAS suppression and greater proteinuria reduction. However, large randomized trials have failed to demonstrate additional benefit in hard renal outcomes and have consistently reported increased risks of hyperkalemia, hypotension, and acute kidney injury. As a result, routine dual RAAS blockade is not recommended in clinical practice. This review summarizes the pathophysiological role of RAAS in CKD, the pharmacological mechanisms and clinical benefits of ACEIs and ARBs, and evidence from major clinical trials. It also highlights safety considerations, current guideline recommendations, and the evolving role of RAAS blockade within a broader therapeutic landscape aimed at slowing CKD progression and improving patient outcomes.