Laboratory Investigation

Kidney International (1987) 31, 1267–1278; doi:10.1038/ki.1987.140

An evaluation of the development of experimental membranous nephropathy

Francis B Gabbai, Leslie C Gushwa, Curtis B Wilson and Roland C Blantz

Department of Medicine, University of California, San Diego, School of Medicine and Veterans Administration Medical Center, San Diego, and Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California, USA

Correspondence: Roland C Blantz MD, Veterans Administration Medical Center, 111H, 3350 La Jolla Village Drive, San Diego, California 92161, USA.

Received 4 March 1986; Revised 12 August 1986.

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Abstract

An evaluation of the development of experimental membranous nephropathy. Heymann nephritis is a rat model of glomerulonephritis with morphologic manifestations of human membranous nephropathy. This model is generated by immunizing rats with Fx1A antigen. Passive Heymann's nephritis (PHN) can be produced by the administration of anti-Fx1A antibody (anti-Fx1A Ab) (with abnormal proteinuria appearing in 5 days). Studies were designed to examine the evolution of temporal changes in protein excretion, the glomerular ultrafiltration coefficient (LpA) and morphology of glomerular capillary three and five days after induction of PHN. Glomerular hemodynamic evaluation by micropuncture in euvolemic rats with PHN revealed normal values for nephron filtration rate (SNGFR), LpA and the glomerular hydrostatic pressure gradient (DeltaP) at day three, but by day five the whole kidney GFR and SNGFR were decreased, DeltaP increased and LpA significantly reduced. Glomerular binding of anti-Fx1A Ab increased from 38 microg/7.6 times 104 glomeruli on day three to 52 microg on day five. Immune complex deposits evaluated by immunofluorescence and electron microscopy appeared larger and were better defined on day five than on day three. Epithelial foot process fusion was more extensive on day five than day three. The onset of increased proteinuria correlated temporally with a reduction in LpA on day five, which in turn correlated with increased antibody binding, immune deposit accumulation and fusion of epithelial cell foot processes.

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