PATHOGENESIS OF MEMBRANOUS GLOMERULONEPHROPATHY

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The objective of this research proposal is to understand more about the pathogeneses of the autologous immune-complex nephropathy of rats (AIC) and of the idiopathic membranous glomerulonephropathy (MGN) in humans. Specifically: 1) we will test the hypothesis that the susceptibility of a species of an animal to develop AIC or of a human to develop MGN is related to the excretion of a brush border antigen (BBAg) in the urine of that species or the individual, 2) develop a more specific radioimmunoassay for measuring BBAg and study in depth the pathogenesis of AIC, 3) determine the ultrastructural location of BBAg in kidney, 4) determine if BBAg is produced by the cultured proximal renal tubules, 5) study the effect of an artifically produced physical-barrier in the glomerular basement membrane induced by the oral administration of silver nitrate on the immune-complex localization in the subepithelial position and 6) study the effect of exogenously given antigen excess as a therapeutic maneuver on the course of AIC. The methods will include immunofluorescence, horseradish peroxidase labelled specific antibodies to BBAg and electron microscopy, culturing of proximal renal tubular cells, radioimmunoassay and column chromatography, etc. Data collected from these experiments will: 1) enhance our knowledge about the pathogenesis of AIC of rats and possibly of MGN in humans, 2) may provide methods to identify individuals susceptible to develop MGN, 3) may lead to methods to treat AIC and possibly MGN and 4) produce information on the role of a physical barrier on the immune-complex deposition in glomerulonephritis.