Clinical meaning
Glomerular filtration rate (GFR) is determined by the net ultrafiltration pressure across the glomerular capillary wall and the ultrafiltration coefficient (Kf, the product of hydraulic permeability and surface area). The glomerulus is uniquely positioned between two arterioles: the afferent arteriole (which delivers blood under pressure) and the efferent arteriole (which creates back-pressure by its relatively higher resistance). Net filtration pressure equals glomerular capillary hydrostatic pressure (~60 mmHg, favoring filtration) minus Bowman capsule hydrostatic pressure (~15 mmHg) minus glomerular capillary oncotic pressure (~28 mmHg, which rises along the capillary length as protein-free filtrate is removed). Tubuloglomerular feedback (TGF) is the primary autoregulatory mechanism: the macula densa in the juxtaglomerular apparatus senses sodium chloride delivery to the distal tubule and modulates afferent arteriolar tone — high NaCl delivery triggers afferent vasoconstriction via adenosine release, reducing GFR, while low delivery causes afferent vasodilation via prostaglandins. ACE inhibitors and ARBs reduce GFR by dilating the efferent arteriole, lowering intraglomerular pressure (their therapeutic mechanism in proteinuric CKD). SGLT2 inhibitors restore TGF by increasing NaCl delivery to the macula densa (normally blunted in diabetes by proximal tubular sodium-glucose hyperreabsorption), causing therapeutic afferent vasoconstriction that reduces glomerular hyperfiltration. Creatinine-based GFR estimation uses the CKD-EPI equation, but creatinine is unreliable in patients with extremes of muscle mass; cystatin C, produced constitutively by all nucleated cells, provides a muscle-mass-independent alternative.