Protein aggregates in extracorporally perfused rabbit kidneys

Eighteen rabbit kidneys were perfused ex vivo for 1 h with allogeneic blood, and in 16 a solution of xenogeneic aggregate-free, aggregated or antibody-complexed protein was added to the perfusate 5 min after the start (human immunoglobulins or serum albumin, partly cationized, were used). The kidneys were examined by light and electron microscopy and the human and rabbit immunoglobulin (or albumin) precipitates were detected by direct immunofluorescence and ultrastructural immunohistochemistry. In 13 kidneys the perfusion produced small segmental glomerular endocapillary aggregates of platelets, leukocytes, and granular precipitates reactive with both anti-rabbit and anti-human antibodies. No typical deposits were seen in mesangium or in periphery of glomerular capillaries but rabbit Ig penetrated to the inter- and subepithelial spaces of proximal convoluted tubules. Three kidneys perfused by cationized aggregated human Ig (or by cationized albumin-antialbumin complexes) exhibited a destructive lesion with rapid breakdown of blood flow and massive global endocapillary plugs of similar ultrastructure but with focal endothelial sloughing. Pericapillary granular precipitates of human and rabbit Ig were seen in these kidneys. When the blood with cationized Ig aggregates was used for perfusion of two further kidneys extensive endocapillary aggregates with endothelial damage reappeared but the extracapillary penetration and precipitation were lacking and the blood flow largely improved. Membrane polyanion of podocytes stained by colloidal iron was preserved even in close proximity of cationized complex precipitates. Thus, in the ex-vivo perfusion model the preformed neutral aggregates did not penetrate through the glomerular capillary wall and were not phagocytized by mesangial cells. The cationized aggregates induced rapid circulatory failure with massive platelet clumping and granular pericapillary "humps" ultrastructurally different from the deposits of human and experimental immune complex glomerulonephritis.