Rejection after simultaneous pancreas–kidney transplantation
1 Department of Surgery, 2 Department of Medicine, Diabetology Center, University of Munich, Munich, Germany and 3 Department of Kidney and Pancreas Transplantation and Organ Procurement, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
Correspondence and offprint requests to: Dr Jacques Malaise, Department of Kidney and Pancreas Transplantation and Organ Procurement, Cliniques Universitaires St Luc, Université Catholique de Louvain, avenue Hippocrate, 10/2207, B-1200 Brussels, Belgium. Email: jacques.malaise{at}chir.ucl.ac.be or Dr Helmut Arbogast, Transplant Centre, Department of Surgery, University of Munich, Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany. Email: helmut.arbogast{at}med.uni-muenchen.de
Background. Simultaneous pancreas–kidney (SPK) transplantation is an 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.
Keywords: cyclosporin microemulsion; kidney–pancreas transplantation; rejection; tacrolimus