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

• 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
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/TP.0b013e3181963371

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.