Tacrolimus exposure in the real world: an analysis from the Mycophenolic acid Observational REnal transplant study

Clin Transplant. 2014 Jul;28(7):768-75. doi: 10.1111/ctr.12377. Epub 2014 May 21.

Abstract

Tacrolimus exposure and renal function data to 36 months post-transplant were analyzed from the prospective, observational Mycophenolic acid Observational REnal transplant (MORE) registry in which de novo kidney transplant patients were managed according to local practice. Tacrolimus trough (C0 ) concentration at month 12 was stratified as low (<6 ng/mL), moderate (6-8 ng/mL), or high (>8 ng/mL) in 724 patients. Estimated glomerular filtration rate (eGFR) was stratified as low (<60 mL/min/1.73 m(2) ) or high (≥60 mL/min/1.73 m(2) ). High tacrolimus C0 (>8 ng/mL) was observed in 47.7%, 34.1%, 26.8%, and 26.7% of patients at baseline and months 12, 24, and 36, respectively. Biopsy-proven acute rejection was similar to month 36 regardless of tacrolimus C0 category at month 12. Tacrolimus C0 >8 ng/mL vs. <6 ng/mL at month 12 was predictive of low eGFR at month 24 (p = 0.023) with a nonsignificant trend at month 36 (p = 0.085). Infections (p < 0.013) and BK virus infection (p < 0.001) were most frequent in the low tacrolimus C0 cohort. Neutropenia was most frequent in the high tacrolimus C0 category (p = 0.010). In conclusion, over a quarter of patients were exposed to high tacrolimus C0 to 36 months post-transplant. Tacrolimus exposure did not affect rejection risk, but tacrolimus C0 >8 ng/mL at month 12 was predictive of subsequent low eGFR compared to C0 <6 ng/mL.

Keywords: Mycophenolic acid Observational REnal transplant; clinical; dose; evolution; exposure; kidney transplantation; reduction; tacrolimus.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Postoperative Complications / drug therapy
  • Postoperative Complications / etiology
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Tacrolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus