Reversible compensatory hypertrophy in rat kidneys: Morphometric characterization

Abstract

Functional renal compensatory hypertrophy (RCH) in the uninephrectomized rat is completely reversible by transplantation in Brown Norway (BN) rats, while anatomic RCH is not. To determine the nephron element(s) responsible for persistent anatomic RCH, we performed morphometric analysis on perfusion fixed rat kidneys following renal function studies. In this model the function of renal transplants is not different from contralateral and unmanipulated control kidneys, and there is no histological evidence of rejection. Rats uninephrectomized for three or six weeks had larger glomeruli than controls, and after transplantation of a previously hypertrophied kidney into a rat with a normal or a solitary hypertrophied kidney, glomerular size returned to control levels. Increased glomerular capillary volume (CV(CP)) in kidneys with RCH was due to increased capillary length (L(CP); 13.1 ± 1.0 mm cf. 10.3 ± 0.9, P < 0.01) without increase in capillary radius (R(CP); 3.26 ± 0.33 μM cf. 3.28 ± 0.24). In contrast, return of CV(CP) to control levels in kidneys undergoing regression was associated with persistently elevated L(CP) (13.0 ± 2.9 mm; native previously hypertrophied kidney; 12.2 ± 0.9; transplanted previously hypertrophied kidney vs. 10.3 ± 0.9, P < 0.01) and decreased R(CP) (2.79 ± 0.10 μM and 2.73 ± 0.09 cf 3.28 ± 0.24, P < 0.01). RCH was associated with proportional increases in glomerular, tubular, and vascular-interstitial volumes while only elevated tubular volume persisted during regression. Altered glomerular capillary dimensions and increased tubular volumes acquired during renal RCH induced by unilateral nephrectomy persisted during complete functional regression. Since CV(CP) increase in RCH is not associated with an increase of R(CP), a pathogenetic role for LaPlace forces based on more extensive models of nephron ablation may not be applicable to the uninephrectomy model.