EHS nephropathy. A long-term morphological and immunohistochemical study.

Abstract

Rats immunized with an emulsion of Engelbreth-Holm-Swarm (EHS) tumour and Freund's complete adjuvant (FCA) excreted large amounts of urinary protein from the 14th week after the initial immunization. The amount of urinary protein increased progressively and, after 1 year, reached over 1 g/day. Kidneys removed from immunized rats at 10 weeks, 24 weeks and 1 year after the initial immunization were examined by immunofluorescence, light and electron microscopy. By immunofluorescence microscopy, granular deposits of rat immunoglobulins (Igs) were observed along the glomerular capillary walls from the 10th week until the end of the observation period. Glomerular membranous transformation was observed from the 24th week by light microscopy. The glomerular capillary walls were thickened and argyrophilic spikes and vacuolations were detected. At 1 year the severity of these changes was increased. Electron microscopic examination showed only a few electron-dense deposits after 10 weeks, but after 24 weeks numerous electron-dense deposits were detected in all glomeruli, the glomerular basement membrane was thickened and irregular and podocyte foot processes were effaced. At 1 year, dense deposits were located intramembranously and their density decreased from the circumference to the centre. Lesions characteristic of human membranous nephritis were observed in this model, the appearances at 10 weeks, 24 weeks and 1 year corresponding to stages I, II and III, respectively, of the classification of Ehrenreich and Churg (1968). Comparison of the immunohistochemical abnormalities in this model and in Heymann nephritis revealed antigenic cross-reactivity; there appears to be common antigenicity between the immune deposits in the glomeruli in both models, cell surface antigens in the EHS tumour and those located in the cell surface antigens in the brush borders of proximal convoluted tubules. Although the antigens responsible have not yet been clearly identified, in this paper I describe a new model of membranous nephritis, tentatively termed EHS nephropathy.