Häyry, P., Ahonen, J., Von Willebrand, E., Eklund, B., Höckekstedt, K., Kauste, A., Taskinen, E., Lautenschlager, I., Lalla, M., and Sarelin, H.
Twenty cadaveric kidney allograft recipients were prerandomized into two groups. Ten patients (control group) were treated postoperatively with azathioprine (AZA) plus methylprednisolone (MP): the other ten received cyclosporin A (CyA) as the only immunosuppressive agent. Both groups received MP during rejection. One patient was excluded from the CyA group because of an early postoperative cardiac infarction and death. All transplants were monitored by alternate-day tine-needle aspiration biopsy and transplant aspiration cytology. Some patients treated with CyA had a significant initial decrease in urine output, reaching control values approximately 1 week postoperatively. The mechanism behind this deteriorated renal function is not clear, but it seemed to have been caused by injuries to the kidney tubular component, since a distinct monocytic-lymphocytic inflammation and severe cytological changes resembling pronounced acute tubular necrosis were observed concomitantly in transplant aspiration cytology. The CyA-treated patients had normal levels of blood leucocytes, thrombocyte and lymphocytes but displayed a strong early blood eosinophilia that was absent in the control subjects. During the first 30 days after transplantation 15 in situ episodes of inflammation were recorded in the nine transplants treated with CyA, whereas only 6 episodes were found in the 10 transplants receiving AZA + MP(P < 0.01). The first inflammatory episode in the CyA-treated transplants peaked between days 5 and 8 after transplantation and was followed by another distinct inflammatory episode between days 23 and 26. In the AZA- plus MP-treated transplants, only one inflammation episode was observed, with a peak on day 14 postoperatively. The inflammatory cell types most prominently present in the CyA-treated transplants were lymphocytes, B plasmablasts and monocytes. The early inflammatory episodes in the CyA-treated transplants may have been related to the fact that during the initial intramuscular administration, therapeutic CyA concentrations in patient serum were not achieved until the fourth postoperative day during peroral administration. The onset of transplant function had no impact on the in situ inflammatory response of rejection in the CyA-treated transplants or on the concentration of CyA in patient serum. This indicates that CyA may also be used in initially nonfunctioning transplants, Confirming our earlier results, we were unable to demonstrate the major histocompatibility complex (MHC) antigens on the healthy grafts treated with AZA plus MP. However, in healthy allografts treated with CyA, both classes of MHC antigens were nearly invariably demonstrable on the graft endothelial cell surface. Approximately 60% allograft survivals were recorded in both groups at 6 months, and all patients with functioning grafts were able to work [ABSTRACT FROM AUTHOR]