NDT Advance Access published online on September 22, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp468
Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation
1 Klinik fuer Visceral, Transplantations, Thorax und Gefaesschirurgie, Universitaetsklinikum Leipzig, Liebigstr. 20, 04103 Leipzig 2 Klinikum Merheim, Medizinische Klinik I, Ostmerheimer Str. 200, 51109 Koeln, Germany 3 Department of Nephrology and Hypertension, Bern University Hospital, Inselspital, CH-3010 Bern, Switzerland 4 Medizinische Klinik—Nephrologie Klinikum Coburg, Ketschendorfer Str. 33, 96450 Coburg 5 Klinik und Poliklinik für Allgemein, Viszeral und Tumorchirurgie, Universitaetsklinikum Koeln, Kerpener Str. 62, 50937 Koeln, Germany 6 Universitaetsklinik für Visceral, Transplantations und Thoraxchirurgie, Universitaetsklinikum Innsbruck, Anichstr. 35, 6020 Innsbruck 7 Allgemeines Krankenhaus Wien Abteilung Nephrologie, Waehringer Guertel 18-20, 1090 Wien, Austria 8 Faculté de Medecine 1, Université de Geneve, Rue Michel-Servet, CH-1211 Geneve 4, Switzerland 9 Klinikum Merheim, Medizinische Klinik, Ostmerheimer Str. 200, 51109 Koeln 10 Department of Nephrology Charité, Universitatsmedizin Berlin, Charitéplatz 1, 10017 Berlin 11 Universitaetsklinikum Aachen, Medizinische Klinik II—Nephrologie Pauwelsstr. 30, 52074 Aachen 12 Klinik IV fuer Innere Medizin, Nephrologie Universitaetsklinikum Koeln, Kerpener Str. 62, 50937 Koeln, Germany
Correspondence and offprint requests to: Josef Fangmann; E-mail: Josef.Fangmann{at}Karl-Olga-Krankenhaus.de
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Abstract |
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Background. Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA.
Methods. We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months.
Results. Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 ± 17) than standard patients (29 ± 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017).
Conclusion. We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions.
Keywords: cyclosporine; daclizumab; immunosuppression; kidney; transplantation
Received for publication: 15. 2.09
Accepted in revised form: 17. 8.09