Intrauterine Growth Restriction following Ligation of the Uterine Arteries Leads to More Severe Glomerulosclerosis after Mesangioproliferative Glomerulonephritis in the Offspring

Background: Low birth weight is a risk factor for the development of a more severe course of secondary renal diseases. We tested the hypothesis that experimental mesangioproliferative glomerulonephritis (GN) shows an aggravated course in rats inflicted with experimental uteroplacental insufficiency during gestation. Methods: Intrauterine growth restriction (IUGR) was induced by ligation of both uterine arteries on day 19 in pregnant Wistar rat dams. GN was induced in male offspring at the age of 9 weeks by intravenous injection of an anti-Thy-1.1 antibody. At day 14 of GN, kidneys were taken and analyzed for glomerular morphometry, markers of inflammation, glomerulosclerosis and tubulointerstitial fibrosis. Results: Despite a similar extent of mesangiolysis, former IUGR animals presented with a higher level of glomerulosclerosis and increased deposition of glomerular collagens I and IV compared to nephritic control animals. Arterial blood pressure, renal function, and proteinuria after 14 days of GN were not influenced by former IUGR. Conclusion: Ligation of the uterine arteries in the rat leads to more pronounced sclerotic changes in the glomerulus in the offspring suffering from acute GN. This finding supports the hypothesis that former IUGR increases the susceptibility for a more severe course of secondary renal diseases. Copyright (C) 2010 S. Karger AG, Basel