[Rejection nephropathy before and after therapeutic administration of cyclosporin A]

During 1983 to 1986 41 patients were treated with Cyclosporin A (CyA) following kidney allotransplantation (TPL). 31 received the first (29 extra- and 2 intrafamilial) graft; in 10 there was second TPL, in 9 cases under high-risk conditions, where the first graft had been destroyed by (hyper)acute rejection or by rapidly progressive rejection with early vascular lesion. 21 needle biopsies and 5 excised grafts which had been collected 5 days to 18 months after TPL were examined by light microscopy and in addition 6 of the former also underwent electron and immunofluorescence microscopic study. The glomeruli showed discrete, inconstant segmental lesions but the ultrastructure also revealed severe general endothelial swelling. The tubular system had nonspecific degenerative changes of varying extent. In 11 patients focal cytoplasmic microvacuoles appeared in proximal tubular epithelia; there were also inconstant hyaline droplets, microcalcifications, and intratubular crystals. Electron microscopy revealed multiple round dense intramitochondrial inclusions in proximal tubules. The ultrastructure of the microvacuoles resembled that of "osmotic nephropathy". The rejection infiltrate and interstitial fibrosis of various degree did not essentially differ from those of conventionally treated grafts. In 7 patients cortical arterioles and small arteries exhibited a stenosing lesion (toxic?). In 3 cases metachromatic "mucoid" thickening of intima was prominent. Ultrastructure studies showed swollen endothelial cells with numerous globular dense bodies and a severe defect in the leiomyofibrils of muscle cells of the media. Hyperplasia of juxtaglomerular apparatus was apparent in 7 patients. Immunofluorescent microscopy of two biopsies from subsequently excised grafts visualized IgM, C3, and fibrinogen in small arteries and some glomerular capillary loops. Three early nephrectomies were caused by infarct-like necrosis. The discussion deals with differences between CyA- and conventionally treated grafts, diagnostic features, interpretation of findings, and measures following biopsy. In our patients with continual CyA-treatment no case of clinically and morphologically typical obliterative arterio-arteriolopathy (OA) and rapidly progressive irreversible rejection has as yet been noted.