Glomerular hemodynamic effects of late pregnancy in rats with experimental membranous glomerulonephropathy

Abstract

In these studies, the Fx1A model of accelerated, passive Heymann nephritis was used to produce membranous glomerulonephropathy. Female rats were studied at 7 wk after the administration of the Fx1A antibody either in the virgin state or in late pregnancy. The goals of these experiments were to determine whether preexisting membranous glomerulonephropathy compromises the pregnancy and whether the pregnancy acutely worsens the renal function. Virgin rats with membranous glomerulonephropathy developed massive proteinuria and exhibited glomerular capillary hypertension but without declines in GFR. In late pregnancy, there was no worsening of the proteinuria and glomerular blood pressure fell to normal values. Both afferent and efferent arteriolar resistances increased in pregnant rats with membranous glomerulonephropathy compared with virgins, leading to falls in glomerular plasma flow and single-nephron GFR. There were no histologic abnormalities in the glomeruli of either virgin or late pregnant rats with membranous glomerulonephropathy, and both groups exhibited similar immunoglobulin G and complement deposits. Up to Day 19 (term is 22 days), the pregnancy in rats with membranous glomerulonephropathy appeared uneventful. Thus, this study indicates that the Fx1A model of membranous glomerulonephropathy does not compromise the course of the pregnancy, at least until close to term. Pregnancy lowers glomerular blood pressure in rats with membranous glomerulonephropathy because of both a fall in systemic blood pressure and the atypical renal vasoconstriction, which leads to declines in single-nephron GFR.