NDT Advance Access originally published online on March 1, 2005
Nephrology Dialysis Transplantation 2005 20(5):968-973; doi:10.1093/ndt/gfh739
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Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2 year follow-up results
1 Klinik und Poliklinik für Innere Medizin II – Nephrologie, University of Regensburg, Germany, 2 Division of Nephrology and Dialysis, Ospedale Maggiore di Milano IRCCS, Milan, Italy, 3 Hospital Reina Sofía, Córdoba, Spain, 4 Landeskrankenhaus, University of Innsbruck, Austria, 5 KfH Nierenzentrum, Jena, Germany, 6 Katharinenhospital, Stuttgart, Germany, 7 Hospital Ramón y Cajal, Madrid, Spain, 8 Universitätsklinik des Saarlandes, Homburg, Germany, 9 Medizin Klinik IV, University of Erlangen, Germany, 10 KH Elisabethinen, Linz, Austria, 11 Hospital Clínico Universitario, Salamanca, Spain, 12 Allgemeines Krankenhaus Wien, University of Vienna, Austria, 13 Hospital Puerta del Mar, Cádiz, Spain and 14 Hospital Marqués de Valdecilla, Santander, Spain
Correspondence and offprint requests to: Prof. Dr Bernhard Krämer, Klinik und Poliklinik für Innere Medizin II – Nephrologie, Klinikum der Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Email: bernhard.kraemer{at}klinik.uni-regensburg.de.
Background. Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and, in some studies, also improves long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection, graft and patient survival and graft function.
Methods. The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a randomized, comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids. The intent-to-treat population (ITT) consisted of 286 patients in the tacrolimus arm and 271 in the CsA microemulsion (CsA-ME) arm. Whereas whole blood level targets were 10–20 and 5–15 ng/ml for tacrolimus and 100–400 and 100–200 ng/ml for CsA during months 0–3 and 4–6, respectively, during the investigator-driven follow-up after termination of the main study (months 7–24) no specific calcineurin inhibitor target levels were required. Follow-up data were collected at 2 years post-transplantation from 237 (82.9% of the ITT population) patients who received tacrolimus and 222 (81.9% of the ITT population) patients who received CsA-ME.
Results. Calculated on ITT populations, mortality (2.0% vs 3.3%; P<0.05 in Kaplan–Meier analysis) was lower, but rate of graft loss (9.3% vs 11.2%; P = 0.12 in Kaplan–Meier analysis) was not significantly different after 2 years with tacrolimus- vs CsA-ME-based immunosuppression. Biopsy-proven acute rejection was significantly lower (19.6%) with tacrolimus than with CsA-ME (37.3%) during months 0–6 (P<0.0001), but was not significantly different during months 7–12 and 13–24 of follow-up (1.7% and 0.8% with tacrolimus and 4.7% and 0.9% with CsA-ME, respectively). A composite endpoint consisting of graft loss, patient death and biopsy-proven acute rejection occurred significantly more frequently in CsA-ME patients than in tacrolimus patients (42.8% vs 25.9%; P<0.001) during 24 months follow-up. Renal function 2 years post-transplant, measured by serum creatinine concentrations, was significantly better in tacrolimus-based compared with CsA-ME-based immunosuppression (136.9 vs 161.6 µmol/l; P<0.01). Cornerstone immunosuppression remained unchanged in 82.5% and 66.2% of patients treated with tacrolimus and CsA-ME, respectively. At 2 years, more patients in the tacrolimus arm were off steroids and received calcineurin inhibitor monotherapy, and fewer tacrolimus patients remained on a triple immunosuppressive regimen. The cardiovascular risk profile was affected favourably in the tacrolimus arm, with lower cholesterol and triglyceride concentrations (despite less use of cholesterol-lowering drugs); no significant difference in requirement for antidiabetic medication was noted.
Conclusions. The 2 year study results confirm that tacrolimus is a highly efficacious cornerstone immunosuppressant in kidney transplantation. Tacrolimus-based immunosuppression may induce long-term benefits with regard to graft function and graft survival. The overall side-effect profile is considered to be favourable.
Keywords: acute rejection; cyclosporin A microemulsion; long-term follow-up; renal function; renal transplantation; tacrolimus
The principal investigators for the Study Group are listed in the ‘Acknowledgements’.
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