Rejection after simultaneous pancreas-kidney transplantation

Background. Simultaneous pancreas-kidney (SPK) transplantation is.-in accepted therapy for type 1 diabetic patients with end-stage renal disease. This study analyses the occurrence of rejection episodes in patients undergoing SPK. Methods. The study population was obtained from 205 patients enrolled in the Euro-SPK 001 study and randomized to receive tacrolimus- (n = 103) or cyclosporin microemulsion (ME)-based (n = 102) immunosuppressive therapy. All patients received concomitant antibody induction therapy, mycophenolate mofetil and short-term corticosteroids. Results. After 3 years of follow-up, rejection episodes occurred in 41 patients receiving tacrolimus and in 51 patients receiving, cyclosporin-ME. The majority of first rejection episodes in both groups occurred during the first 6 months (93 and 90%, respectively) and in most cases were treated with corticosteroids alone (88 vs 90%). Actuarial rejection-free kidney and/or pancreas graft survival was similar for tacrolimus (54%) and cyclosporin-ME (44%). Human leukocyte antigen (HLA) compatibility (P=0.003) and graft vessel extension (P=0.000001) had a significant influence on rejection-Free graft survival. Also, rejection influenced pancreas graft survival (P=0.01), and pancreas graft loss due to rejection influenced patient survival (P=0.02). In the intent-to-treat analysis of early rejection, significantly fewer tacrolimus- than cyclosporin-ME-treated patients had (i) more than one rejection episode (11 out of 40 vs 24 out of 47; P=0.03); (ii) first moderate to severe rejection (one out of 40 vs 12 out of 47; P=0.004); and (iii) refractory rejection (two out of 40 vs 10 out of 47; P=0.03). Pancreas survival was lower in late rejectors (53%) than non-rejectors (86%; P=0.002). Also, serum creatinine was highest in late rejectors. Conclusion. Tacrolimus-based immunosuppressive therapy demonstrates significant advantages over cyclosporin-ME in terms of the severity of acute rejection in SPK transplant patients.