Pharmacology of Cyclosporine in an Ovine Model of Kidney Allograft Rejection.: Abstract# A82

Objective: We sought to develop a clinically relevant large animal model of kidney rejection that responds to the application and withdrawal of immunosuppressant drugs in a predictable manner. Methods: 2 year old sheep were MHC mismatched and underwent a kidney transplant and bilateral nephrectomy. The donor kidney was placed under a skin flap on the neck and anastomosed to the jugular and carotid artery while the ureter was externalized through the skin flap. The sheep was then dosed with cyclosporine for 7 days with the drug being withdrawn on day 8. Blood samples were taken daily and biopsies of the kidney performed every second day. Angiograms of the transplanted kidney were also carried out allowing for visualisation of the blood vessels. Results: Serum creatinine and urea stayed at an acceptable level for the first 7 days post transplantation, upon withdrawal of immunosuppression there was a rapid increase in both serum creatinine and urea consistent with a failing kidney. Likewise, Banff scores from the biopsies were stable for the first 7 days and saw a rapid spike upon withdrawal of cyclosporine as the kidney underwent rejection. Conclusions: The sheep kidney transplant model is a useful large animal model for kidney allograft rejection due to its ability to be MHC mismatched, the ability to use clinically relevant pharmaceutical intervention, and the predictable and pronounced rejection that is able to be easily monitored by renal allograft biopsy. Several imaging techniques, such as MRI to track cells, are also available to use in this model giving it a wide scope for future research.