Glomerular hypertrophy after subtotal nephrectomy: relationship to early glomerular injury

Abstract

Structural adaptations in response to approx. 70% nephrectomy were studied in male Sprague-Dawley rats. Rats developed systemic hypertension as well as progressive albuminuria after nephrectomy. At 18-26 weeks after nephrectomy (n = 6) or sham treatment (n = 6) kidneys were perfusion-fixed and examined by light and electron microscopy. Glomerular tuft volume (+140%), capillary volume (+151%) and length (+77%), mesangial volume (+115%), podocyte volume (+96%), glomerular basement membrane surface area (+107%) and filtration slit length (+85%) were all significantly greater in nephrectomized rats. The incidence of segmental glomerular sclerosis was low and variable among these rats, but was significantly higher than in controls (P = 0.037). Urinary albumin excretion was elevated in the nephrectomized rats (89 +/- 72 SD mg/day vs 11 +/- 11 mg/day in control rats, P = 0.01) and correlated significantly with the incidence of sclerosis (r = +0.8311, P < 0.05). The relationships of the level of albuminuria and the sclerosis rate to various morphometric parameters were examined by regression analysis for the nephrectomy group. A significant negative correlation was found between albuminuria and average tuft volume (r = -0.8136) and glomerular basement membrane surface area (r = -0.8168). Both sclerosis rate and albuminuria showed negative correlations with filtration slit length (r = -0.8180 and r = -0.8598). These findings suggest that under some circumstances, glomerular hypertrophy may prevent or ameliorate the early stages of glomerular injury after subtotal nephrectomy.