Absence of glomerular injury or nephron loss in a normotensive rat remnant kidney model

Abstract

Severe reduction in renal mass (>50%) in the rat uniformly results in progressive glomerular injury and loss of remnant nephrons postulated to be due to increases in glomerular function (hyperfiltration) and/or size (hypertrophy). Reduction in renal mass in the rat also leads to the development of systemic and/or glomerular hypertension. To examine the independent contributions of systemic hypertension and glomerular hyperfiltration and/or hypertrophy to progressive glomerular injury, a normotensive rat remnant kidney model was developed in the Wistar-Kyoto (WKY) strain. Of the 34 WKY rats that underwent 5/6 nephrectomy, 25 remained normotensive and without evidence of morphologic glomerular injury and/or nephron loss for up to 14 to 16 weeks, despite glomerular hyperfiltration and hypertrophy comparable to that previously observed in other rat strains. Micropuncture studies at ∼six weeks after reduction in renal mass demonstrated markedly increased SNGFR in remnant nephrons of normotensive rats as compared to controls (66 ± 7 vs. 25 ± 4 nl/min, P < 0.01), but glomerular capillary pressures (PGC) estimated from stop flow pressures were only slightly increased (52.7 ± 1 vs. 47.3 ± 1 mm Hg, P < 0.01). These data indicate that compensatory glomerular hyperfiltration and hypertrophy after 5/6 nephrectomy may not lead to progressive glomerular injury provided hypertension does not develop. These data further suggest that in the absence of systemic hypertension, increases in PGC required for adaptive hyperfiltration, may not be sufficient to initiate progressive glomerular injury and nephron loss.