THE MESANGIUM IN THE LONG-TERM REMNANT KIDNEY MODEL

Hypertension, which develops during the course of the remnant kidney m odel (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, bu t a separate role for mesangial injury has not been demonstrated in th e absence of systemic hypertension. We studied glomerular injury and m esangial structure and function in a long-term (26 weeks) normotensive rat RK by using morphologic and morphometric studies and mesangial cl earance of aggregated rate IgG (AggRalgG). After right nephrectomy and infarction of two thirds of the left kidney (RK), the rats gained wei ght and developed mild but stable elevations of serum creatinine and u rinary protein excretion as compared with the sham-operated controls ( SHAM) over the course of the study. Systolic blood pressure was only m ildly elevated (129 +/- 9 mm Hg versus 114 +/- 8 mm Hg, p less than or equal to 0.05). Virtually all of the RK rats developed glomerular sca rring, 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 glo meruli in SHAM rats (glomerular diameter 199.3 +/- 15.2 mu m versus 16 0.5 +/- 4.4 mu m, p less than or equal to 0.05), and the accompanying increase in capillary volume was caused by an increase in capillary le ngth without a significant increase in diameter. Despite the glomerula r hypertrophy and increased initial uptake in RK, the mesangial cleara nce of AggRalgG was similar between RK and SHAM rats. We conclude that WKY rats with RK develop a progressive glomerulopathy characterized b y segmental glomerulosclerosis, proteinuria, and mild hypertension. Th e normal mesangial clearance function and the absence of mesangial pat hology in the hypertrophic remnant glomeruli mitigate against a role f or mesangial injury in this form of experimental renal disease.