Mechanisms of glomerular albumin filtration and tubular reabsorption.

Albumin is filtered through the glomerulus with a sieving coefficient of 0.00062, which results in approximately 3.3 g of albumin filtered daily in human kidneys. The proximal convoluted tubule reabsorbs 71%, the loop of Henle and distal tubule 23%, and collecting duct 3% of the glomerular filtered albumin, thus indicating that the kidney plays an important role in protein metabolism. Dysfunction of albumin reabsorption in the proximal tubules, due to reduced megalin expression, may explain the microalbuminuria in early-stage diabetes. Meanwhile, massive nonselective proteinuria is ascribed to various disorders of the glomerular filtration barrier, including podocyte detachment, glomerular basement membrane rupture, and slit diaphragm dysfunction in focal segmental glomerulosclerosis, membranous nephropathy, and other glomerulonephritis. Selective albuminuria associated with foot process effacement and tight junction-like slit alteration is observed in the patients with minimal-change nephrotic syndrome, and the albumin uptake is enhanced in the podocyte cell body, possibly mediated by albumin receptors in the low-dose puromycin model. The role of enhanced podocyte albumin transport needs to be investigated to elucidate the mechanism of the selective albuminuria in minimal-change disease.