title: Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients.
abstract: Sirolimus is used in heart transplant patients with CAV and CNI-induced nephropathy. However, little is known regarding the tolerability, rejection rate, and effect on renal function when used empirically in children. We describe our experience with the empiric use of a sirolimus-based immunosuppressive regimen in pediatric heart transplantation recipients. We reviewed records of patients in whom conversion was attempted to a CNI-free sirolimus-based regimen. Rejection episodes and measures of renal function were recorded. We attempted to convert 20 patients, of which 16 were successful. In total, six of 20 patients (30%) experienced adverse effects. Of the 16 converted, four patients converted to sirolimus due to CNI-induced disease (three nephropathy, one CAV), while 12 patients (mean age 5.5 yr, range 0.1-21 yr; 33% female; 33% with a history of congenital heart disease) were empirically switched to sirolimus at a mean of 2.3 yr after transplant. Follow-up was available for a mean of 2.5 yr after conversion (range 0.5-8.3 yr). The rate of rejection while taking CNIs was 0.18 rejection episodes per patient-year (total of five episodes), compared with 0.03 rejection episodes per patient-year (total of one episode) while on sirolimus. Renal function, in terms of GFR, significantly improved after sirolimus conversion at latest follow-up (from 86 ± 37 mL/min to 130 ± 49 mL/min, p = 0.02). Here, we demonstrate the potential benefit of empiric use of sirolimus in pediatric heart transplant patients in a CNI-free regimen. Larger and longer studies are needed to further clarify risks of rejection and adverse effect profiles.
authors.affiliation: Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Loar
authors.forename: David J
authors.initials: DJ
authors.lastname: Driscoll
authors.forename: Sudhir S
authors.initials: SS
authors.lastname: Kushwaha
authors.forename: Carl H
authors.initials: CH
authors.lastname: Cramer
authors.forename: Patrick W
authors.initials: PW
authors.lastname: O'Leary
authors.forename: Richard C
authors.initials: RC
authors.lastname: Daly
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Mauriello
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D065095:Calcineurin Inhibitors; D002648:Child; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006333:Heart Failure / Q000151:congenital / Q000628:therapy*; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000473:pathology; D008297:Male; D016347:Medical Records Systems, Computerized; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: heart transplantation; immunosuppression; pediatric; sirolimus