Cyclosporine A and azathioprine are equipotent in chronic kidney allograft rejection

Chronic rejection is the major cause of graft loss after kidney transplantation. Various immunosuppressive protocols have been used to ameliorate this process. We investigated whether cyclosporin A- (CyA) or azathioprine- (Aza) based immunosuppression is better able to slow the progression of chronic rejection. Fisher kidneys were transplanted into bilaterally nephrectomized Lewis rats. Recipients received CyA (1.5 mg/kg/day, s.c.) for 10 days, and were treated from day II with either CyA (1.5 mg/kg)+pred (0.15 mg/kg) (C+P), Aza (2 mg/kg) +pred (A+P), vehicle+pred (P), or vehicle alone (controls) (n=8/group). Proteinuria was regularly assessed and grafts were harvested for morphological, immunohistological, and molecular biological analysis at week 24. By week 12 proteinuria had increased to significant levels. At week 24, proteinuria was significantly lower and creatinine clearance was significantly higher in CSP and A+P, than in P or controls. Morphological analysis supported these functional results: at week 24, glomerulopathy, tubular atrophy and intimal proliferation (as assessed according to the BANFF score) were less pronounced in CSP and A+P, as compared with P or controls. These morphological parameters were accompanied by a reduced infiltration of ED-1 + macrophages and CD-5 + T lymphocytes. In P or controls the synthesis of IL-2R alpha mRNB was markedly elevated at this time. In parallel to the reduced cellular infiltration, IL-2R alpha mRNA expression was markedly inhibited, both, in C+P and A+P. There were no significant differences between CSP and A+P regarding the parameters studied. In conclusion, both C+P and A+P reduced the infiltration of activated T lymphocytes, and the pace of chronic kidney allograft rejection. The outcome of C+P and A+P based therapy did not differ significantly.