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dc.contributor.author
Riva, Natalia
dc.contributor.author
Dip, Marcelo
dc.contributor.author
Halac, Esteban
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Guido, Paulo Cáceres
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Woillard, Jean B.
dc.contributor.author
Licciardone, Nieves
dc.contributor.author
Chan, Debora
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Buendía, Jefferson
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Borgnia, Daniela
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Bosaleh, Andrea
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de Davila, María T.
dc.contributor.author
Imventarza, Oscar Cesar
dc.contributor.author
Schaiquevich, Paula Susana
dc.date.available
2020-11-04T15:28:13Z
dc.date.issued
2018-08
dc.identifier.citation
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
dc.identifier.issn
0163-4356
dc.identifier.uri
http://hdl.handle.net/11336/117606
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Lippincott Williams
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ACUTE REJECTION
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ADVERSE DRUG REACTIONS
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MULTIVARIATE ANALYSIS
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PEDIATRIC LIVER TRANSPLANT
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TACROLIMUS
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Otras Ciencias de la Salud
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Ciencias de la Salud
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Survival time to biopsy-proven acute rejection and tacrolimus adverse drug reactions in pediatric liver transplantation
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-02T17:06:12Z
dc.journal.volume
40
dc.journal.number
4
dc.journal.pagination
401-410
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Philadelphia
dc.description.fil
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
dc.description.fil
Fil: Dip, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
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Fil: Halac, Esteban. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Guido, Paulo Cáceres. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Woillard, Jean B.. No especifíca;
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Fil: Licciardone, Nieves. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Chan, Debora. Universidad Tecnológica Nacional; Argentina
dc.description.fil
Fil: Buendía, Jefferson. Universidad de Buenos Aires; Argentina
dc.description.fil
Fil: Borgnia, Daniela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Bosaleh, Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: de Davila, María T.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
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
dc.description.fil
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
dc.journal.title
Therapeutic Drug Monitoring
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://insights.ovid.com/crossref?an=00007691-201808000-00005
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1097/FTD.0000000000000517
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