Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution
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Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution. / Groetzner, Jan; Kaczmarek, Ingo; Schirmer, Johannes; Uberfuhr, Peter; Gulbins, Helmut; Daebritz, Sabine; Meiser, Bruno; Reichart, Bruno.
In: CLIN TRANSPLANT, Vol. 22, No. 5, 08.05.2008, p. 587-593.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution
AU - Groetzner, Jan
AU - Kaczmarek, Ingo
AU - Schirmer, Johannes
AU - Uberfuhr, Peter
AU - Gulbins, Helmut
AU - Daebritz, Sabine
AU - Meiser, Bruno
AU - Reichart, Bruno
PY - 2008/5/8
Y1 - 2008/5/8
N2 - 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 Subsequently, CNIs were completely withdrawn.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.
AB - 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.
KW - Calcineurin Inhibitors
KW - Cyclosporine/adverse effects
KW - Drug Therapy, Combination
KW - Female
KW - Glomerular Filtration Rate
KW - Heart Transplantation/adverse effects
KW - Humans
KW - Immunosuppressive Agents/therapeutic use
KW - Kidney Failure, Chronic/chemically induced
KW - Male
KW - Middle Aged
KW - Mycophenolic Acid/analogs & derivatives
KW - Prospective Studies
KW - Steroids/therapeutic use
KW - Tacrolimus/adverse effects
U2 - 10.1111/j.1399-0012.2008.00828.x
DO - 10.1111/j.1399-0012.2008.00828.x
M3 - SCORING: Journal article
C2 - 18460000
VL - 22
SP - 587
EP - 593
JO - CLIN TRANSPLANT
JF - CLIN TRANSPLANT
SN - 0902-0063
IS - 5
ER -