Glomerular filtration barrier

Glomerulus · GFR 125 mL/min FF 20% Nephrin

Three-layer sieve of fenestrated endothelium, glomerular basement membrane and podocyte foot processes joined by slit diaphragms (nephrin, podocin) that forms an ultrafiltrate of plasma into Bowman's space at ~125 mL/min (180 L/day).

Detail

Filters
Water, electrolytes, glucose, amino acids, urea, small peptides; freely filtered below ~7 kDa, progressively restricted to near zero by ~70 kDa
Excludes
Cells, albumin (69 kDa and negatively charged; heparan sulfate on the GBM repels anions), protein-bound drugs and hormones
GFR
~125 mL/min (180 L/day); filtration fraction = GFR/RPF ~20%
Starling forces
GFR = Kf x [(P_GC - P_BS) - pi_GC]; P_GC ~60 mmHg, P_BS ~15 mmHg, pi_GC ~28 mmHg, net ~17 mmHg outward
Measured by
Inulin clearance (gold standard); creatinine clearance overestimates GFR by ~10-20% because creatinine is also secreted

When it goes wrong

Podocyte foot-process effacement (minimal change disease, FSGS, diabetic nephropathy, membranous nephropathy)

Nephrotic syndrome: proteinuria >3.5 g/day, hypoalbuminaemia, oedema, hyperlipidaemia; selective albuminuria in minimal change

Anti-GBM antibody against the alpha-3 chain of type IV collagen (Goodpasture)

Rapidly progressive crescentic glomerulonephritis with haematuria, red-cell casts and pulmonary haemorrhage

Ureteric obstruction raising Bowman's space pressure

Net filtration pressure and GFR fall despite normal renal perfusion

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