CKD Progression

CKD progression follows a common final pathway regardless of the initial insult. When nephrons are lost, remaining nephrons undergo compensatory hyperfiltration (increased single-nephron GFR) to maintain total GFR temporarily. This maladaptive response involves afferent arteriolar dilation and efferent vasoconstriction (mediated by angiotensin II), increasing intraglomerular pressure and flow. The resulting glomerular hypertension damages the glomerular basement membrane, causes podocyte injury and detachment, and leads to proteinuria. Filtered proteins are toxic to tubular epithelial cells, triggering tubulointerstitial inflammation and fibrosis through TGF-beta, NF-kB, and complement activation. This creates a self-perpetuating cycle: nephron loss → hyperfiltration → glomerular injury → proteinuria → tubulointerstitial fibrosis → more nephron loss. RAAS blockade (ACEi/ARB) and SGLT2 inhibitors interrupt this cycle by reducing intraglomerular pressure.