Mesangial structure and function in the remnant kidney.

The pathogenetic significance of changes in mesangial structure and function were studied in hypertensive (HT) (BP +/- SD = 173 +/- 23 mm Hg, N = 13) and normotensive (NT) (130 +/- 17 mm Hg, N = 12) WKY rats with 5/6 nephrectomy and compared to sham-operated controls (SHAM) (121 +/- 11 mm Hg, N = 12). Rats were fed a 24% protein diet and studied six to eight week after surgery. Acute glomerular necrosis was present in 6/13 HT, 1/12 NT, and 0/12 SHAM, and glomerular sclerosis was seen in 7/13 HT, 4/12 NT, and 0/12 SHAM. HT and NT had glomerular and tubular hypertrophy compared to SHAM (mean glomerular diameter +/- SD. HT = 174 +/- 17 mu and NT = 171 +/- 12 cf. SHAM = 142 +/- 11, P = 0.0012, ANOVA). The fractional mesangial volumes, determined by ultrastructural morphometry, were similar in all groups, but the absolute volumes were increased in the HT and NT (HT = 323 +/- 103 mu3 x 10(-3) and NT = 335 +/- 75 cf. SHAM = 164 +/- 20, P = 0.01, ANOVA). Mesangial clearance of aggregated rat IgG (AgRalgG) was studied in serial biopsies by immunofluorescence microscopy. Following i.v. injection, mesangial AgRalgG appeared increased in HT and NT over SHAM for four hours, but after 24 hours, the label had disappeared from the mesangium in all groups. We conclude that neither increased mesangial volume nor abnormalities of mesangial clearance of macromolecules plays a role in the pathogenesis of the acute, necrotizing glomerular lesion which was mainly seen in HT rats. On the other hand glomerular sclerosis, seen in both NT and HT rats but not sham controls, may result from more than one mechanism. In the HT rats scarring may result from healing of the acute glomerular lesions. Although we have excluded the mesangial clearance function as a factor in the pathogenesis of glomerular sclerosis, the presence of glomerular scarring in NT rats suggests that the lesions may result from dysfunction of other glomerular cells or unmeasured mesangial cell functions.