RAS blockade in chronic kidney disease: Current evidence and future directions

Chronic kidney disease (CKD) is a major global public health issue. The primary causes include diabetes mellitus, hypertension, and glomerular diseases, which involve different pathophysiological and molecular mechanisms, but lead to similar outcomes. In this review, the authors examine the role of pharmacological agents that modify the renin-angiotensin system (RAS) in patients with renal diseases and significant proteinuria. The use of these agents can lead to a reduction in albuminuria and proteinuria, stabilize renal function during follow-up, and slow the progression of the disease. Clinical evidence supports the biological rationale that inhibiting the RAS reduces intraglomerular pressure and mitigates ongoing renal damage. This also underscores the importance of optimal dosing, careful monitoring of electrolytes, and attention to comorbidities to maximize therapeutic benefits in real-world clinical practice, while highlighting the need for further research to refine patient selection and long-term management strategies within an evolving, combination-based therapeutic paradigm. In the contemporary therapeutic landscape, RAS blockade should be viewed as a foundational therapy, primarily driven by cardiovascular protection and proteinuria reduction, upon which newer disease-modifying agents-such as SGLT2 inhibitors-are built. In the contemporary therapeutic landscape, RAS blockade is re-evaluated as a foundational therapy, primarily driven by cardiovascular protection and proteinuria reduction, upon which newer disease-modifying agents-most notably SGLT2 inhibitors-are layered. Future strategies should focus on optimized combination therapy, careful patient selection, and integration of emerging pharmacological pathways to maximize nephroprotection.