The effects of chronic mesangial immune injury on glomerular function
Michels, L.D.; Davidman, M.; Keane, W.F.
Journal of Laboratory and Clinical Medicine 96(3): 396-407
1980
ISSN/ISBN: 0022-2143 PMID: 6447182 Document Number: 166984
The mesangium occupies an intercapillary position in the glomerulus and is a common site of immune complex deposition in human and experimental renal disease. Chronic mesangial injury has been associated with slowly progressive renal insufficiency. In rats, the i.p. administration of ferritin, 8 mg/100 g body wt, daily for 6 wk, results in a reproducible model of mesangial immune complex disease. Whole-kidney and single-nephron function evaluated in 9 experimental and 12 control animals within 1 wk after completion of ferritin immunization. In 7 of 9 experimental animals, circulating antiferritin antibodies were present; the glomerular lesion was characterized by intense mesangial immunofluorescent staining for IgG and C3 were reduced. The glomerular capillary pressure was significantly decreased to 46.3 .+-. 0.8 mm Hg from a control value of 54.8 .+-. 0.9. This fall in glomerular capillary pressure was due to 93% increase in the afferent arteriolar resistance, which rose to 6.2 .+-. 0.5 .times. 1010 dyn .cntdot. s .cntdot. cm-5 from control levels of 3.2 .+-. 0.3, while the efferent arteriolar resistance rose by only 57% from 2.4 .+-. 0.2 to 3.8 .+-. 0.4. Although mean ultrafiltration pressure fell by 66% of control values, SNGFR was reduced by only 40%, indicating that the ultrafiltration coefficient increased in ferritin-treated animals. In the 2 animals that received ferritin for 6 wk and failed to develop an antibody response or demonstrate IgG and C3 in the glomerular mesangium, GFR, SNGFR, SNGPF, glomerular capillary pressure, mean ultrafiltration pressure and the afferent and efferent arteriolar resistances were normal. Mesangial localization of IgG and C3 apparently alters glomerular function primarily as a result of increased afferent and efferent arteriolar resistance.