Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution

• Published in: Clinical transplantation Vol. 22; no. 5; pp. 587 - 593
• Main Authors: Groetzner, Jan, Kaczmarek, Ingo, Schirmer, Johannes, Überfuhr, Peter, Gulbins, Helmut, Daebritz, Sabine, Meiser, Bruno, Reichart, Bruno
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2008; Blackwell
• Subjects: Biological and medical sciences; Calcineurin Inhibitors; cardiac transplantation; Cyclosporine - adverse effects; Drug Therapy, Combination; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glomerular Filtration Rate; Heart Transplantation - adverse effects; Humans; immunosuppression; Immunosuppressive Agents - therapeutic use; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - prevention & control; Male; Medical sciences; Middle Aged; mycophenolate mofetil; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Prospective Studies; Renal failure; Steroids - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tacrolimus - adverse effects; Tissue, organ and graft immunology; Heart; Mofetil; Steroid; Mycophenolic acid; Calcineurin inhibitor; Chronic renal failure; cardiac transplantation; Transplantation; Homotransplantation; Surgery; Treatment withdrawal; Antiviral; Graft; Kidney disease; Corticosteroid; Urinary system disease; Enzyme inhibitor; Conversion; Graft failure; calcineurin inhibitors; Immunomodulator; Medicine; Drug conversion; Antibiotic; Immunosuppression; Treatment; Renal failure; Circulatory system; Immunosuppressive agent; Mycophenolate mofetil
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/j.1399-0012.2008.00828.x

:  Background:  Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)‐based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function.
Methods:  Since 1999, 12 HTx recipients (10 men; 58 ± 3.6 yr of age; 8.7 ± 4.2 yr after HTx) with CNI‐based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2–4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter.
Results:  After a mean follow‐up of 20 ± 16 months, CreaCl improved significantly: pre‐conversion vs. post‐conversion: 32.8 ± 12.2 mg/dL vs. 42.8 ± 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients.
Conclusions:  Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection.