Secondary effects of immunosuppressive drugs after simultaneous pancreas–kidney transplantation
1 Department of Nephrology and Renal Transplantation and 3 Department of Abdominal Transplantation Surgery, University Hospitals Leuven, Leuven and 2 Kidney and Pancreas Transplantation Unit, 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
Background. This report examines the early and late secondary effects of tacrolimus, cyclosporin microemulsion (ME), mycophenolate mofetil (MMF) and rabbit anti-thymocyte globulin (rATG) in simultaneous pancreas–kidney (SPK) recipients.
Methods. Of the 205 patients participating in the Euro-SPK 001 study, 103 were randomized to tacrolimus (0.2 mg/kg) and 102 to cyclosporin-ME (7 mg/kg). All patients received rATG for 4 days [ATG-Fresenius (ATG-F) 4 mg/kg/day or Thymoglobulin (Thymo-S) 1.25 mg/kg/day] plus MMF and short-term corticosteroids.
Results. Thymo-S induction therapy was associated with a lower white cell count in the first 3 months than was seen with ATG-F, while ATG-F caused a lower initial nadir in platelet count. Both polyclonal preparations were well tolerated and no clinically relevant differences were observed with respect to side effects such as infections and malignancies. High cyclosporin-ME trough levels were associated with pancreas graft thrombosis, and concentrations >150 ng/ml were associated with poor renal allograft function. Treatment discontinuation was higher with cyclosporin-ME (57.8%) than with tacrolimus-based therapy (36.9%) due to more frequent toxicity, graft loss and lack of efficacy requiring a switch to tacrolimus. The main reason for withdrawal in the tacrolimus group was MMF discontinuation; MMF-related side effects resulted in more frequent dose reductions to <2 g/day and discontinuations in the tacrolimus group, and indirectly indicate a higher dose-corrected exposure to mycophenolic acid, as previously observed in kidney transplant patients.
Conclusions. Short-term induction therapy is effective and well tolerated in patients undergoing SPK transplantation. Tacrolimus was the preferred immunosuppressive agent, resulting in fewer cases of pancreas graft loss and drug discontinuation compared with cyclosporin-ME.
Keywords: ATG; cyclosporin microemulsion; kidney–pancreas transplantation; MMF; multicentre study; tacrolimus