Clinical meaning
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.
Diagnosis & workup
Diagnostics & workup: - eGFR trajectory: calculate rate of decline; >5 mL/min/year is rapid progression requiring investigation - Serial UACR monitoring: increasing proteinuria indicates accelerating nephron damage - Renal ultrasound: progressive decrease in kidney size indicates chronic scarring - Kidney biopsy: if cause of CKD unclear or rapidly progressive decline - Monitor for complications as GFR declines: anemia (Hgb, iron studies), mineral bone disease (Ca, PO4, PTH, vitamin D), metabolic acidosis (HCO3) - 24-hour urine protein if UACR is borderline or to quantify protein loss precisely