The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation

Shelly Lichtenberg, Ruth Rahamimov, Hefziba Green, Benjamin D. Fox, Eytan Mor, Uzi Gafter, Avry Chagnac, Benaya Rozen-Zvi

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case–control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. Methods: We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. Results: Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1–9) and 11.7 (95% CI = 1.3–106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3–20.5) and 14.1 (95% CI = 1.5–134.3), respectively, for cancer diagnosed more than 3 years after transplantation. Conclusion: Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

Original languageEnglish
Pages (from-to)819-826
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume73
Issue number7
DOIs
StatePublished - 1 Jul 2017

Keywords

  • Immunosuppressive drugs
  • Malignancy
  • Tacrolimus
  • Transplantation

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