Improvement of renal function in pediatric heart transplant recipients treated with low-dose calcineurin inhibitor and mycophenolate mofetil.
BACKGROUND
Renal dysfunction is a major complication in heart transplant recipients treated with calcineurin inhibitors. The goal of the study was to investigate the effect of a reduction of calcineurin inhibitor dosage with the concomitant introduction of mycophenolate mofetil on both renal function and cardiac allograft function.


METHODS
Fourteen of 52 consecutive pediatric cardiac allograft recipients experienced a progressive decrease of renal function. A renal biopsy was performed before the dose of calcineurin inhibitors was reduced by 50% and azathioprine was replaced by mycophenolate mofetil. Renal function was evaluated by inulin clearance and maximal urinary osmolality before and yearly after the therapeutic changes. Acute rejection was monitored clinically, by echocardiography and endomyocardial biopsies.


RESULTS
Inulin clearance in the fourteen children decreased from 84.2 mL/min/1.73 m at one year posttransplantation to 46.5+/-9.6 mL/min/1.73 m at the time of the change in immunosuppressive therapy. Significant renal lesions were observed in the renal biopsies performed before the change. At 1 year, inulin clearance had increased by 67%. In six patients who had a second determination 2 years after the switch, inulin clearance was not significantly different from the value at 1 year. There were three reversible acute rejection episodes in three patients. The incidence of rejection episodes was not different from a control group of patients whose treatment was not changed.


CONCLUSIONS
The reduction of calcineurin inhibitor dosage and replacement of azathioprine by mycophenolate mofetil is a safe way to improve renal function in children with heart transplants and calcineurin inhibitor induced nephrotoxicity.
Boyer
Olivia
O
Service de Néphrologie Pédiatrique, Hôpital Necker Enfants Malades, Paris, France.
Le Bidois
Jérôme
J
Dechaux
Michèle
M
Gubler
Marie-Claire
MC
Niaudet
Patrick
P
D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011446:Prospective Studies; D019233:Retreatment; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus