Mycophenolate mofetil and sirolimus as calcineurin inhibitor-free immunosuppression for late cardiac-transplant recipients with chronic renal failure

• Published in: Transplantation Vol. 77; no. 4; pp. 568 - 574
• Main Authors: GROETZNER, Jan, MEISER, Bruno, LANDWEHR, Peter, BUEHSE, Lucia, MUELLER, Markus, KACZMAREK, Ingo, VOGESER, Michael, DAEBRITZ, Sabine, UEBERFUHR, Peter, REICHAET, Bruno
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 27-02-2004
• Subjects: Adult; Biological and medical sciences; Calcineurin Inhibitors; Cardiovascular System - physiopathology; Dose-Response Relationship, Drug; Female; Heart - physiopathology; Heart Transplantation; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Kidney - physiopathology; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - physiopathology; Male; Medical sciences; Middle Aged; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - adverse effects; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - blood; Mycophenolic Acid - therapeutic use; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Renal failure; Sirolimus - administration & dosage; Sirolimus - adverse effects; Sirolimus - therapeutic use; Time Factors; Heart; Mofetil; Graft(material); Mycophenolic acid; Calcineurin inhibitor; Sirolimus; Calcineurin; Transplantation; Homotransplantation; Surgery; Graft; Failure; Kidney disease; Late; Urinary system disease; Recipient; Antibiotic; Chronic; Immunosuppression; Treatment; Urinary system; Renal failure; Inhibitor; Circulatory system; Immunosuppressive agent; Mycophenolate mofetil; Antibacterial agent
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/01.TP.0000103740.98095.14

Calcineurin-inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this study was to introduce a CNI-free immunosuppressive regimen to HTx recipients with late posttransplant renal impairment and to evaluate the impact of conversion to this new immunosuppression (mycophenolate mofetil [MMF] and sirolimus [Sir]) treatment on renal function.
Thirty-one HTx patients (25 men, 6 women; 0.2-14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine greater than 1.9 mg/dL were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Mean patient age was 50+/-14 (range 19-74) years. Conversion was started with 6 mg Sir, continued with 2 mg, and the dose was adjusted to achieve target trough levels between 8 and 14 ng/mL. MMF was continued with trough level adjusted (1.5-4 microg/mL). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up (first and every 3 months after conversion) included endomyocardial biopsies, echocardiography, and laboratory studies. Survival was 90% after a mean follow-up of 13+/-95 months. No acute rejection episode was detected during the study period. Renal function improved significantly after conversion: creatinine preconversion vs. postconversion: 3.14+/-0.76 mg/dL vs. 2.14+/-0.83 mg/dL, P =0.001. Cystatin preconversion vs. postconversion: 2.95+/-1.06 mg/L vs. 2.02+/-1.1 mg/L, P =0.01. In three patients, hemodialysis therapy was stopped completely after conversion. Graft function remained stable. Fractional shortening preconversion vs. postconversion: 36.9+/-6% vs. 36.4+/-6%. There were no serious adverse events. One patient had to be excluded because of noncompliance.
Conversion from CNI-based immunosuppression to MMF and Sir in HTx patients with chronic renal failure was safe, preserved graft function, and improved renal function.