Immunosuppression switch in pediatric heart transplant recipients: cyclosporine to FK 506.
OBJECTIVE
We studied rejection, allograft function and side effects, such as hypertension, renal dysfunction and hypercholesterolemia, in seven patients switched from cyclosporine-based triple-drug immunosuppression to FK 506.


BACKGROUND
A subset of pediatric heart transplant recipients treated with triple-drug immunosuppression consisting of cyclosporine, azathioprine and prednisone experience either persistent rejection when attempts are made to taper corticosteroids or morbidity from cyclosporine and corticosteroids. Experience with the new immunosuppressive agent FK 506 has demonstrated its effectiveness as a single agent in heart transplant recipients, and anecdotal evidence has shown that side effects such as hypertension and hypercholesterolemia may be lower.


METHODS
Seven patients whom we deemed corticosteroid dependent were switched to FK 506-based therapy. Allograft function, episodes of rejection, need for corticosteroids and incidence of side effects from FK 506 were monitored. The switch to FK 506 was performed using an established protocol. Follow-up time has ranged from 15 to 41 months. Serial right heart catheterizations and endomyocardial biopsies were performed after each reduction of corticosteroid dosing.


RESULTS
Catheterization data showed no significant change in pulmonary wedge pressure, mean right atrial pressure or cardiac index, indicating no decline in allograft function. Serial echocardiographic variables of allograft function were also stable. At present, all seven patients are free of the corticosteroid portion of their immune suppression. There have been only two episodes of significant acute rejection requiring treatment with intravenous corticosteroids. Antihypertensive medications have been discontinued in five of six patients previously treated with these drugs. Plasma cholesterol, low density lipoprotein and triglyceride levels were decreased, and renal function was stable.


CONCLUSIONS
Preliminary studies suggest that FK 506 may be an alternative immunosuppressive agent for pediatric and adolescent patients experiencing ongoing rejection or significant morbidity from cyclosporine and corticosteroids and in those patients dependent on corticosteroids for immune suppression.
Swenson
J M
JM
Department of Pediatric Cardiology and Cardiac Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh, Pennsylvania 15213.
Fricker
F J
FJ
Armitage
J M
JM
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D006328:Cardiac Catheterization; D002648:Child; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007165:Immunosuppression Therapy; D007674:Kidney Diseases / Q000139:chemically induced; D008232:Lymphoproliferative Disorders / Q000139:chemically induced; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D000959:Antihypertensive Agents; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone; D016559:Tacrolimus