Glomerular Filtration Barrier

Mnemonic

Three layers, from blood to urine:

• Fenestrated endothelium - excludes cells
• Glomerular basement membrane - type IV collagen and heparan sulphate, providing the negative charge barrier
• Podocyte foot processes with slit diaphragms (nephrin, podocin), providing the size barrier

“Endothelium stops cells, basement membrane stops charge, podocytes stop size.”

The barrier is therefore selective for both size and charge: albumin is only 69 kDa and could pass on size alone, but it is negatively charged and is repelled.

Each layer maps onto a disease: anti-GBM disease (Goodpasture’s) attacks the type IV collagen; minimal change disease effaces the podocyte foot processes, visible only on electron microscopy; and loss of the charge barrier explains the selective albuminuria of early diabetic nephropathy.

Expansion

Three layers, from blood to urinary space:

1. Fenestrated endothelium - pores of 70 to 100 nm, excluding cells
2. Glomerular basement membrane - type IV collagen and negatively charged heparan sulphate proteoglycans
3. Podocyte foot processes with filtration slits bridged by nephrin and podocin

Selectivity is by size and charge:

• Molecules under about 10 kDa pass freely
• Above about 70 kDa, filtration is negligible
• Negatively charged molecules such as albumin (69 kDa) are repelled by the negatively charged barrier, so filtration is far lower than size alone predicts

Disease maps onto the layers:

• Minimal change disease: loss of charge and podocyte foot process effacement, giving highly selective albuminuria
• Alport syndrome: a type IV collagen defect in the basement membrane
• Goodpasture disease: antibodies against the basement membrane
• Congenital nephrotic syndrome: nephrin mutations