Pathogenesis of glomerular injury in the fawn-hooded rat: Early glomerular capillary hypertension predicts glomerular sclerosis

Fawn-hooded rats spontaneously develop focal and segmental glomerular sclerosis, systemic hypertension, and proteinuria at a young age. Micropuncture and morphological studies were performed in two inbred strains of fawn-hooded rats, FHH and FHL, with different susceptibilities to develop chronic renal failure. FHH rats have higher values for systolic blood pressure and proteinuria and more rapid development of focal and segmental glomerular sclerosis and subsequent chronic renal failure as compared with genetically closely related FHL rats. FHH and FHL strains and a Wistar control strain, WAG, were matched for age and were studied at 16 wk. FHH, FHL, and WAG-old (WAG-O) strains were matched for weight, and the last group was studied at 22 wk. WAG were also matched for weight to a young group of FHH rats (FHH-Y), and these were studied at 8 wk. In comparison with WAG and WAG-O rats, FHH and FHH-Y rats exhibited an increase in mean glomerular capillary hydraulic pressure (WAG, 52 ± 1 mm Hg; WAG-O, 47 ± 2 mm Hg; FHH, 60 ± 2 mm Hg; FHH-Y, 65 ± 1 mm Hg), whereas values in FHL animals were intermediate (56 ± 2 mm Hg). No significant differences in glomerular volume were found among groups. Moderate focal and segmental glomerular sclerosis developed in FHH and FHH-Y rats, with values for older FHH rats being significantly greater than those for WAG, WAG-O, and FHL animals. Thus, the genetically determined sensitivity to develop proteinuria, focal and segmental glomerular sclerosis, and chronic renal failure in fawn-hooded rats correlated with early evidence of glomerular capillary hypertension. By contrast, glomerular hypertrophy was not associated with and was not a prerequisite for early glomerular injury in fawn-hooded rats.