Role of glomerular epithelial cell injury in the pathogenesis of glomerular scarring in the rat remnant kidney model.
We investigated the roles of glomerular epithelial cell (GEC) pathology and dysfunction in the pathogenesis of glomerular scarring and attempted to separate them from direct hypertensive injury in the 5/6 nephrectomy (RK) model of glomerular injury. Male WKY rats weighing 200 g were studied 6 weeks after RK, when approximately one-half had developed systemic hypertension (systolic blood pressure > or = 150 mm Hg) (HT), and one-half were normotensive (NT). The incidence of glomerular necrosis and scarring was greatest in the HT rats (P = 0.0259), and vascular necrosis was only seen in 4 of 11 HT rats. The RK group had increased glomerular diameters (HT, 174 mu mean; NT, 171 mu; sham, 142 mu; P = 0.0014 by analysis of variance). There was foot process effacement in the HT and NT groups (HT, 104 filtration slits/100 mu glomerular basement membrane; NT, 112 mu; sham, 143 mu; P < 0.005 by analysis of variance), but GEC separation from the glomerular basement membrane was not significant in either HT or NT rats. GEC function was determined from protamine-heparin aggregate disappearance curves, and the curves, representing GEC endocytosis, were not different in either HT or NT groups compared with the sham-operated groups. These findings suggest that GEC function is preserved in RK, and the changes in glomerular size and GEC morphology are nonlethal and adaptive. The morphological appearance of the acute glomerular and vascular lesions and their presence only in HT animals is consistent with a hypertensive pathogenesis. The glomerular sclerosis seen in both HT and NT may result from either resolution of acute lesions with scarring and/or adaptive changes in glomerular structure and cellular functions other than the GEC clearance function we studied.
Schwartz
M M
MM
Department of Pathology, Rush Medical College, Chicago, IL 60612.
Bidani
A K
AK
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004195:Disease Models, Animal; D004705:Endocytosis; D004848:Epithelium / Q000473:pathology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY