Mycophenolate and Sirolimus as Calcineurin Inhibitor-Free Immunosuppression Improves Renal Function Better Than Calcineurin Inhibitor-Reduction in Late Cardiac Transplant Recipients With Chronic Renal Failure
| Autor: | VENINAHTx-Investigators, Justus T. Strauch, Meinolf Voss, Karrl Christian Koch, Emilia Stegemann, Bruno Meiser, Hermann Reichenspurner, Uwe Schulz, Thorsten Wahlers, Sabine Daebritz, Johannes Schirmer, Christof Schmid, Kristina Kaiser, Ingo Kaczmarek, Jan Groetzner, Jochen Mueller-Ehmsen, Florian Wagner, Hans-Ulrich Stempfle, Hae-Young Sohn, Michael Vogeser, Gero Tenderich, Bruno Reichart, Thorsten Wittwer |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Calcineurin Inhibitors Urology Renal function Kidney Kidney Function Tests Mycophenolic acid medicine Humans Aged Sirolimus Transplantation business.industry Patient Selection Immunosuppression Middle Aged Mycophenolic Acid medicine.disease Surgery Heart Transplantation Kidney Failure Chronic Trough level Female Hemodialysis business Immunosuppressive Agents medicine.drug Kidney disease |
| Zdroj: | Transplantation. 87:726-733 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/tp.0b013e3181963371 |
| Popis: | Background Calcineurin-inhibitor-(CNI)-induced renal failure is one major cause of morbidity in cardiac transplantation (HTx). In this prospective, randomized, multicenter trial, the impact of immunosuppressive conversion toward CNI-free (mycophenolate mofetil [MMF] and sirolimus) or a CNI-reduced immunosuppressive regimen on renal function, efficacy, and safety was evaluated. Methods Since 2004, 63 HTx-patients (0.5-18.4 years after HTx) with CNI-based immunosuppression and reduced creatinine clearance less than 60 mL/min (39+/-15 mL/min) were included in this trial. Patients in the CNI-free-Group (group 1) were converted to sirolimus that was started with 2 mg/day until target trough levels (8-14 ng/mL) were achieved. Subsequently, CNIs were withdrawn. In CNI-reduction-Group (group 2), CNI target trough levels were reduced by 40%. In both groups MMF was continued and trough level adjusted (1.5-4 microg/mL). Results Patients demographics and survival (mean follow-up time: 16.7+/-9 months) was equal (100%). Renal function improved significantly after complete CNI withdrawal while remaining unchanged with CNI-reduction (Creatinine clearance after 12 months: 53+/-24 mg/dL [group 1] vs. 38+/-20 mg/dL [group 2], P=0.01). End-stage renal failure (hemodialysis) was avoided by CNI-withdrawal and occurred only after CNI reduction (n=6; P=0.01). Acute rejection episodes were more common in group 2 (4 vs. 2). Graft function remained stable (echocardiography) within both groups. Adverse events were more common in group 1 (65%) than in group 2 (n=40%) and were responsible for discontinuation in 4 and 0 cases, respectively. Conclusions Conversion toward a CNI-free immunosuppression (Mycophenolate, sirolimus) is superior to CNI-reduced immunosuppression in improving renal failure in late HTx-recipients. However, this benefit is relativized by the increased incidence and severity of sirolimus/MMF-associated side effects. |
| Databáze: | OpenAIRE |
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