A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation

Nauras Shuker*, Lamis Shuker, Joost van Rosmalen, Joke I. Roodnat, Lennaert C.P. Borra, Willem Weimar, Dennis A. Hesselink, Teun van Gelder

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

108 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1158-1167
Number of pages10
JournalTransplant International
Volume29
Issue number11
DOIs
Publication statusPublished - Nov 2016

Bibliographical note

Funding
This study was supported by an unrestricted grant from
Chiesi Pharmaceuticals

Publisher Copyright:
© 2016 Steunstichting ESOT

Research programs

  • EMC MM-04-39-05
  • EMC NIHES-01-66-01
  • EMC OR-01-34-01

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