Pathophysiology
Clinical meaning
Chronic kidney disease (CKD) involves progressive and irreversible loss of nephron function, staged by GFR from Stage 1 (GFR ≥ 90 with kidney damage markers) through Stage 5 (GFR < 15, end-stage renal disease requiring dialysis or transplantation). As nephrons are destroyed, surviving nephrons undergo compensatory hyperfiltration and hypertrophy, which paradoxically accelerates glomerulosclerosis through increased intraglomerular pressure. The renin-angiotensin-aldosterone system (RAAS) plays a central role in CKD progression: angiotensin II causes efferent arteriolar constriction, increasing glomerular pressure and proteinuria, which triggers tubular inflammation and fibrosis. ACE inhibitors and ARBs are renoprotective because they reduce intraglomerular pressure and proteinuria, slowing CKD progression independent of their blood pressure-lowering effect.