Limitations of podocyte adaptation for glomerular injury in puromycin aminonucleoside nephrosis.

Glomerular synechiae that occurred in nephrotic rats with a single intraperitoneal injection of puromycin aminonucleoside were analyzed by immunohistochemistry, radiolabeled thymidine ([3H]-thymidine) autoradiography, as well as light, electron and immunoelectron microscopy. To discriminate podocytes from parietal epithelial cells (PEC) and monocytes, monoclonal antibodies (mAb) against podocalyxin and ED1 were used. The cell kinetics of glomerular epithelial cells were autoradiographically assessed with isotope labeling procedures before and during nephrosis (co-labeled), and a mAb against proliferating cell nuclear antigen (PCNA). All the cell types except the podocyte of normal kidneys were labelled with [3H]-thymidine at different rates. Detachment of degenerated podocytes from the outside of the glomerular basement membrane (GBM) is the first step of synechia, and detached sites are confronted by PEC that were hypertrophied and frequently radiolabeled. Evidence that podocytes in glomeruli of nephrotic rats can proliferate was shown by the presence of mitoses, [3H]-thymidine uptake in the co-labeled experiment, and by PCNA staining, but re-epithelialization over bare segments of the GBM with proliferated podocytes is doubtful. It was concluded that glomerular synechia resulted from the limits of podocyte adaptation to glomerular injuries.