Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution.
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 Subsequently, CNIs were completely withdrawn.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.
Groetzner
Jan
J
Department of Cardiac Surgery, Ludwig Maximilians University Hospital Grosshadern, Munich, Germany. jgroetzner@t-online.de
Kaczmarek
Ingo
I
Schirmer
Johannes
J
Uberfuhr
Peter
P
Gulbins
Helmut
H
Daebritz
Sabine
S
Meiser
Bruno
B
Reichart
Bruno
B
D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D013256:Steroids / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus