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

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 immunosuppre...

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Published in:	Transplantation Vol. 87; no. 5; pp. 726 - 733
Main Authors:	GROETZNER, Jan, KACZMAREK, Ingo, SOHN, Hae-Young, WAGNER, Florian, MEISER, Bruno, REICHART, Bruno, TENDERICH, Gero, STEMPFLE, Hans-Ulrich, MUELLER-EHMSEN, Jochen, SCHMID, Christof, VOGESER, Michael, KOCH, Karri Christian, SCHULZ, Uwe, REICHENSPURNER, Hermann, DAEBRITZ, Sabine, STEGEMANN, Emilia, KAISER, Kristina, WITTWER, Thorsten, SCHIRMER, Johannes, VOSS, Meinolf, STRAUCH, Justus, WAHLERS, Thorsten
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 15-03-2009
Subjects:	Adult Aged Biological and medical sciences Calcineurin Inhibitors Female Fundamental and applied biological sciences. Psychology Fundamental immunology Heart Transplantation - immunology Humans Immunosuppressive Agents - therapeutic use Kidney - drug effects Kidney - immunology Kidney Failure, Chronic - complications Kidney Failure, Chronic - immunology Kidney Function Tests Male Medical sciences Middle Aged Mycophenolic Acid - analogs & derivatives Mycophenolic Acid - therapeutic use Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Patient Selection Renal failure Sirolimus - therapeutic use Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tissue, organ and graft immunology Antineoplastic agent Heart Mycophenolic acid Renal function Calcineurin inhibitor Chronic renal failure Sirolimus Transplantation Homotransplantation Macrocycle Improvement Reduction Surgery Antiviral Graft Protein synthesis inhibitor Kidney disease Late Urinary system disease Lactone Macrolide Graft failure Immunomodulator Antibiotic Immunosuppression Treatment Circulatory system Immunosuppressive agent Antibacterial agent
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Summary:	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. 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). 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. 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.
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ISSN:	0041-1337 1534-6080
DOI:	10.1097/TP.0b013e3181963371