Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: A lesson learned from DeKAF Genomics

Ajay K. Israni, Samy M. Riad, Robert Leduc, William S. Oetting, Weihua Guan, David Schladt, Arthur J. Matas, Pamala A. Jacobson

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Most calcineurin inhibitor (CNI)-based protocols reduce blood trough goals approximately 2-3 months post-transplant in clinically stable kidney transplant recipients. The CNI target trough level to prevent rejection, after reduction, is unknown. Using a multivariate Cox proportional hazards model, we determined the association of time-varying tacrolimus (TAC) trough levels with acute rejection (AR) occurring in the first 6 months post-transplant, but specifically we assessed this association after 3 months. A total of 1930 patients received TAC-based immunosuppression prior to AR in a prospective study. Of the 151 (7.8%) who developed AR, 47 developed AR after 3 months post-transplant. In an adjusted time-varying multivariate model, each 1 ng/ml decrease in TAC trough levels was associated with a 7.2% increased risk of AR [hazards ratio (HR) = 1.07, 95% confidence interval (CI) (1.01, 1.14) P = 0.03] in the first 6 months. There was an additional 23% increased risk of AR with each 1 ng/ml decrease in the TAC trough levels in months 3-6 [HR = 1.23, 95% CI (1.06, 1.43) P = 0.008]. In conclusion, lower TAC trough levels were significantly associated with increased risk of AR in the first 6 months post-transplant with additional risk of AR between months 3 and 6 post-transplant. The timing and practice of TAC dose reduction should be personalized based on the individual's risk factors.

Original languageEnglish (US)
Pages (from-to)982-989
Number of pages8
JournalTransplant International
Volume26
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • acute rejection
  • kidney transplant
  • tacrolimus reduction
  • trough levels

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