mTOR inhibitors in pediatric liver transplant recipients.
Adolescent
Child
Child, Preschool
Cyclosporine
Everolimus
/ administration & dosage
Female
Humans
Immunosuppressive Agents
/ administration & dosage
Infant
Liver
Male
Retrospective Studies
Sirolimus
/ administration & dosage
Steroids
/ therapeutic use
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Tacrolimus
/ therapeutic use
Transplant Recipients
liver transplantation
mTOR inhibitor
outcome
pediatric
Journal
Clinics and research in hepatology and gastroenterology
ISSN: 2210-741X
Titre abrégé: Clin Res Hepatol Gastroenterol
Pays: France
ID NLM: 101553659
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
27
06
2018
revised:
05
11
2018
accepted:
09
11
2018
pubmed:
12
12
2018
medline:
7
7
2020
entrez:
12
12
2018
Statut:
ppublish
Résumé
During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). The aim of the present study was to describe the use of mTORi in pediatric LT recipients. All pediatric LT recipients who received mTORi before December 2017 from 4 European pediatric LT centers were included and analyzed. The present retrospective study included 30 patients; 21 were male (70%), median age was 9.3 years (range: 1.2-17.1 years) at mTORi introduction. Main indications for mTORi introduction were pre-existing liver malignancy (43.3%), calcineurin inhibitor (CNI) nephrotoxicity (26.7%), or rejection (23.4%). At last follow-up, mTORi CNIs were withdrawn in 10 patients (10/29, 34.5%). The median dose of mTORi was 1.8 mg/day (range: 0.3-5.0) or 0.058 mg/kg/day (range: 0.01-0.26), and the median trough level was 5.1 μg/L (range: 1.0-15.5). After a median follow-up of 2.8 years (range: 0.2-10.0), 50.0% of the patients presented with at least one adverse event. The main adverse events included hyperlipidemia, proteinuria, dermatitis, and mucitis. Overall mTORi discontinuation rate was 23.3% (10.0% because of adverse event). Introduction of mTORi had no significant impact on renal function. Our results suggest that mTORi can be used in pediatric LT recipients in different clinical situations, both to reinforce immunosuppressive therapy, and to reduce CNI and related toxicity.
Sections du résumé
BACKGROUND
During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). The aim of the present study was to describe the use of mTORi in pediatric LT recipients.
METHODS
All pediatric LT recipients who received mTORi before December 2017 from 4 European pediatric LT centers were included and analyzed.
RESULTS
The present retrospective study included 30 patients; 21 were male (70%), median age was 9.3 years (range: 1.2-17.1 years) at mTORi introduction. Main indications for mTORi introduction were pre-existing liver malignancy (43.3%), calcineurin inhibitor (CNI) nephrotoxicity (26.7%), or rejection (23.4%). At last follow-up, mTORi CNIs were withdrawn in 10 patients (10/29, 34.5%). The median dose of mTORi was 1.8 mg/day (range: 0.3-5.0) or 0.058 mg/kg/day (range: 0.01-0.26), and the median trough level was 5.1 μg/L (range: 1.0-15.5). After a median follow-up of 2.8 years (range: 0.2-10.0), 50.0% of the patients presented with at least one adverse event. The main adverse events included hyperlipidemia, proteinuria, dermatitis, and mucitis. Overall mTORi discontinuation rate was 23.3% (10.0% because of adverse event). Introduction of mTORi had no significant impact on renal function.
CONCLUSION
Our results suggest that mTORi can be used in pediatric LT recipients in different clinical situations, both to reinforce immunosuppressive therapy, and to reduce CNI and related toxicity.
Identifiants
pubmed: 30528864
pii: S2210-7401(18)30267-5
doi: 10.1016/j.clinre.2018.11.010
pii:
doi:
Substances chimiques
Immunosuppressive Agents
0
Steroids
0
Cyclosporine
83HN0GTJ6D
Everolimus
9HW64Q8G6G
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Tacrolimus
WM0HAQ4WNM
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
403-409Informations de copyright
Copyright © 2018 Elsevier Masson SAS. All rights reserved.