Renin-Angiotensin System Polymorphism in Chronic Kidney Disease and Diabetic Nephropathy

Abstract

The renin-angiotensin system (RAS) is a vital hormonal pathway that regulates blood pressure, fluid balance and vascular tone but its dysregulation has been linked to several renal ailments including chronic kidney disease (CKD) and diabetic nephropathy (DN). Angiotensin II, the key effector molecule of RAS, acts through receptors AGTR1 and AGTR2 thus influencing cell proliferation, inflammation, and angiogenesis. Current review summarizes the key RAS gene variations associated with CKDs. Genetic polymorphisms in RAS components particularly ACE (I/D), AGTR1 (A1166C), and AGT (M235T) have been associated with increased susceptibility and progression of renal diseases. In CKDs, ACE DD and AGTR1 CC genotypes correlate with higher ACE activity, hypertension, and faster disease progression highlighting their diagnostic and therapeutic significance. Hyperglycemia induced RAS activation has been associated with DN through elevation of Ang II levels. The elevated Ang II leads towards oxidative stress and vascular injury. Overall, RAS genetic polymorphism plays a central role in renal disease pathogenesis, hence offering valuable insight for personalized medicine and targeted therapy.