Glomerular damage after uninephrectomy in young rats. I. Hypertrophy and distortion of capillary architecture

Abstract

Uninephrectomy (UNX) results in a higher incidence of focal glomerular sclerosis (FGS) in young rats than it does in adults. The reason for this higher susceptibility in young animals is not fully understood, but this does suggest that UNX in young rats may represent a particularly promising model in which to study the development of FGS. In the present study 10-day-old rats were subjected to UNX. After 4, 12 and 24 weeks, glomerular hypertrophy, structural lesions and function were analyzed in comparison with sham-operated controls. Up to the twelfth week, remnant kidney growth and glomerular growth proceeded in parallel; thereafter, kidney growth ceased, whereas glomerular growth continued undiminished. Twenty-four weeks after UNX, glomerular tuft volume in experimental animals exceeded that in controls by 80%. Twelve weeks after surgery, total GFR in UNX rats was approximately 80% of that in controls, a value maintained until the end of the observation period. Twenty-four weeks after surgery, heavy proteinuria was present in UNX animals. Structural abnormalities in glomeruli of UNX animals were already encountered 12 weeks after surgery; they were present to a much lesser extent in controls. In UNX animals these proceeded to the FGS stage by the end of the observation period. Three major groups of glomerular lesions were observed: (1) changes in the width and shape of glomerular capillaries. (2) changes in podocyte structure, and (3) tuft adhesions to Bowman's capsule with or without segmental sclerosis. The structural changes are analyzed in this and an accompanying paper [1]. The present paper deals with the widespread formation of irregular, giant capillary loops. They occur predominantly at the tuft periphery with a clear predilection for the vascular pole region. They are not a result of compensatory growth, but rather an expansion of single capillaries due to failure of the mesangium. Local disconnection of the mesangium from its anchoring points at the GBM leads to bulging and "coalescence" of capillary loops, resulting in abnormally-shaped vascular channels. This process is associated with a rearrangement of the corresponding mesangium. In our view, the appearance of dilated capillaries represents a local event pivotal to the development of more severe lesions, such as tuft adhesions and FGS.