Renal recovery after conversion to a calcineurin inhibitor-free immunosuppression in late cardiac transplant recipients.
OBJECTIVE
Calcineurin inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this prospective study was to evaluate the safety and efficacy of a completely CNI-free immunosuppressive regimen [mycophenolate mofetil (MMF) and sirolimus (Sir)] in HTx-recipients with late post-transplant renal impairment.


METHODS
Since 2001, 30 HTx-patients (25 men, 6 women; 0.2-14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine >1.9 mg/dl were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Conversion was started with 6 mg Sir or 500 mg MMF according to the pre-existing regimen and was continued with the dose adjusted to achieve target trough levels between 8 and 14 ng/ml (Sir) or 1.5 and 4 microg/ml (mycophenolate). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up included endomyocardial biopsies, echocardiography and laboratory studies. Additionally, every HTx-patient treated at our centre between 1996 and 2001 due to chronic renal failure without immunosuppressive conversion and fulfilling the inclusion criteria were retrospectively analysed and acted as control group.


RESULTS
Patient demographics and 1-year survival [93 (conversion) vs 90% (control)] were compared. No acute rejection episode was detected in either group. Renal function improved significantly in the conversion group (creatinine: 3.18+/-0.71 vs 2.22+/-0.79 mg/dl, P=0.001; cystatin pre- vs post-conversion: 2.95+/-1.06 vs 2.02+/-1.1 mg/l, P=0.01). In three patients haemodialysis therapy was stopped completely after conversion. In the control group renal impairment was deteriorating, creatinine increased from 2.44+/-0.8 to 3.28+/-1 mg/dl (P=0.01). In 10 out of 33 patients chronic haemodialysis had to be initiated within 1 year. Although side effects of CNI-free immunosuppression were common (76%), no patient had to be excluded due to adverse effects.


CONCLUSIONS
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.
Groetzner
Jan
J
Department of Cardiac Surgery, Ludwig Maximilians University Hospital Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany. jan.groetzner@med.uni-muenchen.de
Kaczmarek
Ingo
I
Landwehr
Peter
P
Mueller
Markus
M
Daebritz
Sabine
S
Lamm
Peter
P
Meiser
Bruno
B
Reichart
Bruno
B
D001794:Blood Pressure / Q000187:drug effects; D065095:Calcineurin Inhibitors; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000139:chemically induced / Q000517:prevention & control; D011446:Prospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus