The mesangium in the long-term remnant kidney model

Hypertension, which develops during the course of the remnant kidney model (RK), plays a major role in the pathogenesis of glomerular injury. Morphologic studies have implicated mesangial injury and dysfunction in the pathogenesis of glomerular scarring in the hypertensive RK, but a separate role for mesangial injury has not been demonstrated in the absence of systemic hypertension. We studied glomerular injury and mesangial structure and function in a long-term (26 weeks) normotensive rat RK by using morphologic and morphometric studies and mesangial clearance of aggregated rate IgG (AggRaIgG). After right nephrectomy and infarction of two thirds of the left kidney (RK), the rats gained weight and developed mild but stable elevations of serum creatinine and urinary protein excretion as compared with the sham-operated controls (SHAM) over the course of the study. Systolic blood pressure was only mildly elevated (129 +/- 9 mm Hg versus 114 +/- 8 mm Hg, p < or = 0.05). Virtually all of the RK rats developed glomerular scarring, with segmental sclerosis in 8% +/- 8% and global sclerosis in 2% +/- 2% of the glomeruli, whereas the SHAM animals had no glomerular scarring, but we found limited morphologic evidence of mesangial cell injury in RK. The RK glomeruli were hypertrophied as compared with glomeruli in SHAM rats (glomerular diameter 199.3 +/- 15.2 microns versus 160.5 +/- 4.4 microns, p < or = 0.05), and the accompanying increase in capillary volume was caused by an increase in capillary length without a significant increase in diameter. Despite the glomerular hypertrophy and increased initial uptake in RK, the mesangial clearance of AggRaIgG was similar between RK and SHAM rats. We conclude that WKY rats with RK develop a progressive glomerulopathy characterized by segmental glomerulosclerosis, proteinuria, and mild hypertension. The normal mesangial clearance function and the absence of mesangial pathology in the hypertrophic remnant glomeruli mitigate against a role for mesangial injury in this form of experimental renal disease.