Glomerular albumin filtration through podocyte cell body in puromycin aminonucleoside nephrotic rat

It is an a priori concept that protein molecules including albumin are filtrated through the slit membrane between the foot processes of podocytes. However, foot processes are effaced and the number of slit membranes is reduced in nephrotic syndrome, suggesting another pathway of albumin filtration through the foot process cell body. Thus, we investigated the pathway of gold-and fluorescein isothiocyanate (FITC)-labeled albumin filtration in the puromycin aminonucleoside (PAN) model of nephrotic syndrome in the rat. PAN rats at day 7 with established nephrotic proteinuria were injected with 8-nm gold-labeled albumin and FITC-labeled albumin through the jugular vein followed by kidney fixation at 10 or 30 min. Goldlabeled albumin was accumulated in the paramesangial area and in the endosomes of glomerular endothelial cells of both control and PAN rats by electron microscopy. On the other hand, FITC-labeled albumin was detected between foot processes in the control but more in the podocyte cell body in the PAN rat. In conclusion, albumin will be filtrated through the decreased numbers of slit diaphragms; however, albumin can be also taken up in the podocyte, the mesangium, and the glomerular endothelium, suggesting that there might be other routes of glomerular albumin clearance in nephrotic syndrome.