AN EXPERIMENTAL-MODEL OF CHRONIC RENAL-ALLOGRAFT REJECTION IN THE RATUSING TRIPLE-DRUG IMMUNOSUPPRESSION

Background. Chronic rejection is a major problem in renal transplantat ion. Various experimental models have been developed to study vasculop athy of chronic rejection, However, animal models resembling the clini cal situation of renal transplantation with combination therapy of bas ic immunosuppression are not available, The aim of this study was to f ind an experimental model of a donor-recipient rat strain combination that, under triple drug immunosuppressive treatment (methylprednisolon e, cyclosporine, and azathioprine), would develop chronic rejection wi thin a few weeks, Methods. Renal transplantations were performed in st rain combinations of DA-->AO, PVG-->BN, and DA-->BN. In each group, 5- 8 animals received triple drug treatment of methylprednisolone (2 mg/k g), azathioprine (2 mg/kg), and cyclosporine (5 mg/kg) daily, 5-10 ani mals were left without treatment, and 6 syn genic transplantations wer e performed. The grafts were monitored with ultrasound-guided fine nee dle aspiration biopsies to quantify the inflammation in the graft, Gra ft histology was performed in parallel and quantified by using the chr onic allograft damage index (CADI). Results. In nonimmunosuppressed an imals, irreversible acute rejection with a high peak of inflammation a ppeared in every strain combination within 5-8 days, In triple drug-tr eated rats, the DA-->AO combination demonstrated a prolonged acute rej ection but no characteristic chronic changes, and the PVG-->BN combina tion showed practically no inflammation and did not develop any signs of chronic rejection within 60 days (CADI: 2.7 +/- 2.1), but the DA--> BN combination showed an early, mild inflammatory response 5 - 7 days after transplantation and developed chronic rejection within 40 - 60 d ays after transplantation (CADI: 7.9 +/- 3.1). Syngenic animals showed no inflammation or histological alterations (CADI: 1.7 +/- 2.0), Conc lusions, In conclusion, in the DA-->BN combination with triple drug tr eatment, early mild inflammation was followed by the development of ch ronic rejection and can be used as an experimental model that resemble s the clinical situation in renal transplantation.