Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation

Autores
Riva, Natalia; Dip, Marcelo; Halac, Esteban; Guido, Paulo Cáceres; Woillard, Jean B.; Licciardone, Nieves; Chan, Debora; Buendía, Jefferson; Borgnia, Daniela; Bosaleh, Andrea; de Davila, María T.; Imventarza, Oscar Cesar; Schaiquevich, Paula Susana
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients. Methods: We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity. ADR- and AR-free survival rates were calculated using the Kaplan–Meier method, and risk factors were identified by multivariate Cox regression models. Results: Cox-proportional hazard models identified that high tortuosity in tacrolimus C0 was associated with an 80% increased risk of AR [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.01–3.22; P, 0.05], whereas steroid in maintenance doses decreased this risk (HR, 0.56; 95% CI, 0.31–0.99; P, 0.05). Forty-six patients experienced at least one ADR including hypomagnesemia, nephrotoxicity, hypertension, malignancies, and tremor as a first event. Multivariate analysis showed that C0 values 10 days before the event (HR, 1.25; 95% CI, 1.21–1.39; P, 0.0001) and CYP3A5 expresser recipients (HR, 2.05; 95% CI, 1.03–4.06; P, 0.05) were independent predictors of ADR. Conclusions: Tacrolimus C0 values, its variability, and CYP3A5 polymorphisms were identified as risk factors of AR and tacrolimus ADR. This knowledge may help to control and reduce their incidence in pediatric liver transplant patients. Prospective studies are important to validate these results.
Fil: Riva, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dip, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Halac, Esteban. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Guido, Paulo Cáceres. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Woillard, Jean B.. No especifíca;
Fil: Licciardone, Nieves. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Chan, Debora. Universidad Tecnológica Nacional; Argentina
Fil: Buendía, Jefferson. Universidad de Buenos Aires; Argentina
Fil: Borgnia, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Bosaleh, Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: de Davila, María T.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Imventarza, Oscar Cesar. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Materia
ACUTE REJECTION
ADVERSE DRUG REACTIONS
MULTIVARIATE ANALYSIS
PEDIATRIC LIVER TRANSPLANT
TACROLIMUS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/117606
Acceder
id CONICETDig_54b76d147a13784e84501402ac0dd0fe
oai_identifier_str oai:ri.conicet.gov.ar:11336/117606
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantationRiva, NataliaDip, MarceloHalac, EstebanGuido, Paulo CáceresWoillard, Jean B.Licciardone, NievesChan, DeboraBuendía, JeffersonBorgnia, DanielaBosaleh, Andreade Davila, María T.Imventarza, Oscar CesarSchaiquevich, Paula SusanaACUTE REJECTIONADVERSE DRUG REACTIONSMULTIVARIATE ANALYSISPEDIATRIC LIVER TRANSPLANTTACROLIMUShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients. Methods: We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity. ADR- and AR-free survival rates were calculated using the Kaplan–Meier method, and risk factors were identified by multivariate Cox regression models. Results: Cox-proportional hazard models identified that high tortuosity in tacrolimus C0 was associated with an 80% increased risk of AR [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.01–3.22; P, 0.05], whereas steroid in maintenance doses decreased this risk (HR, 0.56; 95% CI, 0.31–0.99; P, 0.05). Forty-six patients experienced at least one ADR including hypomagnesemia, nephrotoxicity, hypertension, malignancies, and tremor as a first event. Multivariate analysis showed that C0 values 10 days before the event (HR, 1.25; 95% CI, 1.21–1.39; P, 0.0001) and CYP3A5 expresser recipients (HR, 2.05; 95% CI, 1.03–4.06; P, 0.05) were independent predictors of ADR. Conclusions: Tacrolimus C0 values, its variability, and CYP3A5 polymorphisms were identified as risk factors of AR and tacrolimus ADR. This knowledge may help to control and reduce their incidence in pediatric liver transplant patients. Prospective studies are important to validate these results.Fil: Riva, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dip, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Halac, Esteban. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Guido, Paulo Cáceres. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Woillard, Jean B.. No especifíca;Fil: Licciardone, Nieves. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Chan, Debora. Universidad Tecnológica Nacional; ArgentinaFil: Buendía, Jefferson. Universidad de Buenos Aires; ArgentinaFil: Borgnia, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Bosaleh, Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: de Davila, María T.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Imventarza, Oscar Cesar. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaLippincott Williams2018-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/117606Riva, Natalia; Dip, Marcelo; Halac, Esteban; Guido, Paulo Cáceres; Woillard, Jean B.; et al.; Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation; Lippincott Williams; Therapeutic Drug Monitoring; 40; 4; 8-2018; 401-4100163-4356CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/crossref?an=00007691-201808000-00005info:eu-repo/semantics/altIdentifier/doi/10.1097/FTD.0000000000000517info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:48Zoai:ri.conicet.gov.ar:11336/117606instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:48.307CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
title Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
spellingShingle Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
Riva, Natalia
ACUTE REJECTION
ADVERSE DRUG REACTIONS
MULTIVARIATE ANALYSIS
PEDIATRIC LIVER TRANSPLANT
TACROLIMUS
title_short Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
title_full Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
title_fullStr Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
title_full_unstemmed Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
title_sort Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
dc.creator.none.fl_str_mv Riva, Natalia
Dip, Marcelo
Halac, Esteban
Guido, Paulo Cáceres
Woillard, Jean B.
Licciardone, Nieves
Chan, Debora
Buendía, Jefferson
Borgnia, Daniela
Bosaleh, Andrea
de Davila, María T.
Imventarza, Oscar Cesar
Schaiquevich, Paula Susana
author Riva, Natalia
author_facet Riva, Natalia
Dip, Marcelo
Halac, Esteban
Guido, Paulo Cáceres
Woillard, Jean B.
Licciardone, Nieves
Chan, Debora
Buendía, Jefferson
Borgnia, Daniela
Bosaleh, Andrea
de Davila, María T.
Imventarza, Oscar Cesar
Schaiquevich, Paula Susana
author_role author
author2 Dip, Marcelo
Halac, Esteban
Guido, Paulo Cáceres
Woillard, Jean B.
Licciardone, Nieves
Chan, Debora
Buendía, Jefferson
Borgnia, Daniela
Bosaleh, Andrea
de Davila, María T.
Imventarza, Oscar Cesar
Schaiquevich, Paula Susana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACUTE REJECTION
ADVERSE DRUG REACTIONS
MULTIVARIATE ANALYSIS
PEDIATRIC LIVER TRANSPLANT
TACROLIMUS
topic ACUTE REJECTION
ADVERSE DRUG REACTIONS
MULTIVARIATE ANALYSIS
PEDIATRIC LIVER TRANSPLANT
TACROLIMUS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients. Methods: We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity. ADR- and AR-free survival rates were calculated using the Kaplan–Meier method, and risk factors were identified by multivariate Cox regression models. Results: Cox-proportional hazard models identified that high tortuosity in tacrolimus C0 was associated with an 80% increased risk of AR [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.01–3.22; P, 0.05], whereas steroid in maintenance doses decreased this risk (HR, 0.56; 95% CI, 0.31–0.99; P, 0.05). Forty-six patients experienced at least one ADR including hypomagnesemia, nephrotoxicity, hypertension, malignancies, and tremor as a first event. Multivariate analysis showed that C0 values 10 days before the event (HR, 1.25; 95% CI, 1.21–1.39; P, 0.0001) and CYP3A5 expresser recipients (HR, 2.05; 95% CI, 1.03–4.06; P, 0.05) were independent predictors of ADR. Conclusions: Tacrolimus C0 values, its variability, and CYP3A5 polymorphisms were identified as risk factors of AR and tacrolimus ADR. This knowledge may help to control and reduce their incidence in pediatric liver transplant patients. Prospective studies are important to validate these results.
Fil: Riva, Natalia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Dip, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Halac, Esteban. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Guido, Paulo Cáceres. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Woillard, Jean B.. No especifíca;
Fil: Licciardone, Nieves. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Chan, Debora. Universidad Tecnológica Nacional; Argentina
Fil: Buendía, Jefferson. Universidad de Buenos Aires; Argentina
Fil: Borgnia, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Bosaleh, Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: de Davila, María T.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Imventarza, Oscar Cesar. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
description Background: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients. Methods: We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity. ADR- and AR-free survival rates were calculated using the Kaplan–Meier method, and risk factors were identified by multivariate Cox regression models. Results: Cox-proportional hazard models identified that high tortuosity in tacrolimus C0 was associated with an 80% increased risk of AR [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.01–3.22; P, 0.05], whereas steroid in maintenance doses decreased this risk (HR, 0.56; 95% CI, 0.31–0.99; P, 0.05). Forty-six patients experienced at least one ADR including hypomagnesemia, nephrotoxicity, hypertension, malignancies, and tremor as a first event. Multivariate analysis showed that C0 values 10 days before the event (HR, 1.25; 95% CI, 1.21–1.39; P, 0.0001) and CYP3A5 expresser recipients (HR, 2.05; 95% CI, 1.03–4.06; P, 0.05) were independent predictors of ADR. Conclusions: Tacrolimus C0 values, its variability, and CYP3A5 polymorphisms were identified as risk factors of AR and tacrolimus ADR. This knowledge may help to control and reduce their incidence in pediatric liver transplant patients. Prospective studies are important to validate these results.
publishDate 2018
dc.date.none.fl_str_mv 2018-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/117606
Riva, Natalia; Dip, Marcelo; Halac, Esteban; Guido, Paulo Cáceres; Woillard, Jean B.; et al.; Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation; Lippincott Williams; Therapeutic Drug Monitoring; 40; 4; 8-2018; 401-410
0163-4356
CONICET Digital
CONICET
url http://hdl.handle.net/11336/117606
identifier_str_mv Riva, Natalia; Dip, Marcelo; Halac, Esteban; Guido, Paulo Cáceres; Woillard, Jean B.; et al.; Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation; Lippincott Williams; Therapeutic Drug Monitoring; 40; 4; 8-2018; 401-410
0163-4356
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/crossref?an=00007691-201808000-00005
info:eu-repo/semantics/altIdentifier/doi/10.1097/FTD.0000000000000517
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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