Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients

Robert W. Loar, David J. Driscoll, Sudhir S. Kushwaha, Carl H. Cramer, Patrick W. O'Leary, Richard C. Daly, Daniel A. Mauriello, Jonathan N. Johnson

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)794-799
Number of pages6
JournalPediatric Transplantation
Volume17
Issue number8
DOIs
StatePublished - Dec 2013

Fingerprint

Sirolimus
Heart Transplantation
Immunosuppression
Pediatrics
Transplants
Kidney
Calcineurin Inhibitors
Immunosuppressive Agents
Heart Diseases

Keywords

  • heart transplantation
  • immunosuppression
  • pediatric
  • sirolimus

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Transplantation

Cite this

Loar, R. W., Driscoll, D. J., Kushwaha, S. S., Cramer, C. H., O'Leary, P. W., Daly, R. C., ... Johnson, J. N. (2013). Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients. Pediatric Transplantation, 17(8), 794-799. https://doi.org/10.1111/petr.12163

Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients. / Loar, Robert W.; Driscoll, David J.; Kushwaha, Sudhir S.; Cramer, Carl H.; O'Leary, Patrick W.; Daly, Richard C.; Mauriello, Daniel A.; Johnson, Jonathan N.

In: Pediatric Transplantation, Vol. 17, No. 8, 12.2013, p. 794-799.

Research output: Contribution to journalArticle

Loar, RW, Driscoll, DJ, Kushwaha, SS, Cramer, CH, O'Leary, PW, Daly, RC, Mauriello, DA & Johnson, JN 2013, 'Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients', Pediatric Transplantation, vol. 17, no. 8, pp. 794-799. https://doi.org/10.1111/petr.12163
Loar, Robert W. ; Driscoll, David J. ; Kushwaha, Sudhir S. ; Cramer, Carl H. ; O'Leary, Patrick W. ; Daly, Richard C. ; Mauriello, Daniel A. ; Johnson, Jonathan N. / Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients. In: Pediatric Transplantation. 2013 ; Vol. 17, No. 8. pp. 794-799.
@article{76cc09f528f5494bb725f8edef79b24c,
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.",
keywords = "heart transplantation, immunosuppression, pediatric, sirolimus",
author = "Loar, {Robert W.} and Driscoll, {David J.} and Kushwaha, {Sudhir S.} and Cramer, {Carl H.} and O'Leary, {Patrick W.} and Daly, {Richard C.} and Mauriello, {Daniel A.} and Johnson, {Jonathan N.}",
year = "2013",
month = "12",
doi = "10.1111/petr.12163",
language = "English (US)",
volume = "17",
pages = "794--799",
journal = "Pediatric Transplantation",
issn = "1397-3142",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients

AU - Loar, Robert W.

AU - Driscoll, David J.

AU - Kushwaha, Sudhir S.

AU - Cramer, Carl H.

AU - O'Leary, Patrick W.

AU - Daly, Richard C.

AU - Mauriello, Daniel A.

AU - Johnson, Jonathan N.

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

KW - heart transplantation

KW - immunosuppression

KW - pediatric

KW - sirolimus

UR - http://www.scopus.com/inward/record.url?scp=84886860837&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886860837&partnerID=8YFLogxK

U2 - 10.1111/petr.12163

DO - 10.1111/petr.12163

M3 - Article

C2 - 24164828

AN - SCOPUS:84886860837

VL - 17

SP - 794

EP - 799

JO - Pediatric Transplantation

JF - Pediatric Transplantation

SN - 1397-3142

IS - 8

ER -