Glomerular epithelial cell function and pathology following extreme ablation of renal mass

The role of the pathologic features and dysfunction of glomerular epithelial cells (GECs) in the pathogenesis of glomerular scarring was studied in the remnant kidney model (RK) (1 and 5/6 nephrectomy) in rats. Three weeks after surgery serum creatinine was greater in the RK than either sham-operation controls (SHAM) or spontaneously hypertensive rats (SHRs). Blood pressure was higher in the RK (181 +/- 26 mm Hg) than in SHAM (129 +/- 17, P less than 0.05) but not SHR (195 +/- 15, P less than 0.05). GEC endocytosis, assessed by protamine heparin aggregate (PHA) disappearance (10), was not different from that in SHAM. Glomerular damage was greater in RK (glomerular damage index, 30 +/- 18) than in SHAM animals (4 +/- 3, P less than 0.05) and SHR (0, P less than 0.05), and 2 of 11 RK animals had fibrinoid necrosis and thrombosis of arterioles and glomeruli. Segmental sclerosis occurred in only 1 RK animal (0.6% of glomeruli). Six weeks after surgery serum creatinine and urinary protein excretion remained higher in the RK than in the SHAM animals. Blood pressure was higher in RK (158 +/- 34 mm Hg) than in SHAM animals (144 +/- 24), but the difference was not significant. PHA disappeared from the glomerulus at a slower rate in RK than in SHAM animals (outside the 95% confidence limits of SHAM). Glomerular pathology was more widespread in RK than in SHAM animals (glomerular damage index, 73 +/- 62 versus 3 +/- 8, P less than 0.05), and 4 of 11 animals had acute hypertensive injury in arterioles and glomeruli. Segmental glomerular sclerosis was only seen in the animals with necrotic glomeruli. GEC dysfunction is not demonstrable until long after proteinuria and hypertension are established, and it only occurs in the context of severe, acute glomerular injury when the epithelial cells separate from the capillary wall and undergo severe degenerative changes and necrosis. The acute glomerular and vascular lesions in the RK model are morphologically similar to malignant nephrosclerosis in humans. Segmental glomerular sclerosis occurs only after proteinuria is well established in the context of severe glomerular injury, and it appears to represent, at least partially, progression of more proximate glomerular capillary injury.