Experimental ablation nephropathy. Fine structure, morphometry, cell membrane epitopes, glomerular polyanion and effect of subsequent transplantation.

The subtotal (5/6) nephrectomy performed in 23 adult female rats induced severe hypertrophy of residual parenchyma with interstitial fibrosis, tubular dilatation, and focal and segmental glomerulosclerosis (FSG). This ablation nephropathy (AbN) caused proteinuria, progressive renal failure, and hypertension. The extent of FSG was assessed by semiquantitative scoring. The ultrastructure revealed widespread foot process fusion, many dense cytoplasmic inclusions in podocytes, and degenerative changes or disruption of mesangium with glomerular "microcysts". Numerous granular deposits of rat Ig were seen in the glomeruli but a short praeterminal i.v. load by heat-aggregated human Ig did not alter the morphology of AbN and produced discrete and inconstant glomerular deposits. Similarly an i.v. injection of protamine and heparin generated protamine-heparin complexes seen in various layers of glomerular capillary wall, similar to those found previously in normal rats. AbN displayed a partial irregular depletion of polyanion sites reactive with polyethylenimine in lamina rara externa. A significant increase in both glomerular and interstitial Ia+ cells and a marked predominance of W3/25+ cells in the interstitial infiltrates were documented by immunohistochemistry in the remnant kidneys. Both AbN and FSG could be largely corrected (or prevented?) by subsequent syngeneic renal transplantation (TPL; 6 animals). On the other hand a severe AbN was found in two post-ablation residues after unsuccessful TPL with graft necrosis or sclerosis.--AbN has some analogies to various chronic human nephropathies (e.g. FSG) and may explain their progression to the terminal failure. Degenerative and finally destructive mesangial lesion seems to be of prime importance in AbN.