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A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation.
Shuker, Nauras; Shuker, Lamis; van Rosmalen, Joost; Roodnat, Joke I; Borra, Lennaert C P; Weimar, Willem; Hesselink, Dennis A; van Gelder, Teun.
Afiliação
  • Shuker N; Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. n.shuker@erasmusmc.nl.
  • Shuker L; Department of Hospital Pharmacy, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. n.shuker@erasmusmc.nl.
  • van Rosmalen J; Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
  • Roodnat JI; Department of Biostatistics, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
  • Borra LC; Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
  • Weimar W; Department of Hospital Pharmacy, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
  • Hesselink DA; Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
  • van Gelder T; Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
Transpl Int ; 29(11): 1158-1167, 2016 Nov.
Article em En | MEDLINE | ID: mdl-27188932
Tacrolimus is a critical dose drug with a considerable intrapatient variability (IPV) in its pharmacokinetics. We investigated whether a high IPV in tacrolimus exposure is associated with adverse long-term renal transplantation outcomes. Tacrolimus IPV was calculated from predose concentrations measured between 6 and 12 months post-transplantation of 808 renal transplant recipients (RTRs) transplanted between 2000 and 2010. One hundred and eighty-eight (23.3%) patients reached the composite end point consisting of graft loss, late biopsy-proven rejection, transplant glomerulopathy, or doubling of serum creatinine concentration between month 12 and the last follow-up. The cumulative incidence of the composite end point was significantly higher in patients with high IPV than in patients with low IPV (hazard ratio: 1.41, 95% CI: 1.06-1.89; P = 0.019). After the adjustment for several factors, the higher incidence of the composite end point for RTRs with a high IPV remained statistically significant (hazard ratio: 1.42, 95% CI: 1.06-1.90; P = 0.019). Younger recipient age at transplantation, previous transplantation, worse graft function (at month 6 post-transplantation), and low mean tacrolimus concentration at 1 year post-transplantation were additional predictors for worse long-term transplant outcome. A high tacrolimus IPV is an independent risk factor for adverse kidney transplant outcomes that can be used as an easy monitoring tool to help identify high-risk RTRs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Tacrolimo / Insuficiência Renal Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Transpl Int Assunto da revista: TRANSPLANTE Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Rim / Tacrolimo / Insuficiência Renal Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Transpl Int Assunto da revista: TRANSPLANTE Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Holanda