Tacrolimus and Mycophenolic Acid Blood Concentration and Cellular Rejection After Heart Transplantation in First Endomyocardial Biopsy

Transplant Proc. 2020 Sep;52(7):2094-2097. doi: 10.1016/j.transproceed.2020.03.006. Epub 2020 Jun 20.

Abstract

Background: Tacrolimus and mycophenolic acid (MPA) are the most important immunosuppressive drugs in modern heart transplantation. The pharmacokinetics of tacrolimus are best described by a 2-compartment model. MPA has very variable pharmacokinetics. The aim of this research was to compare kinetics of the immunosuppressants' blood levels in a group of patients with and without graft rejection.

Materials and methods: The study was a retrospective analysis of 39 consecutive adult orthotopic heart transplantations (OHT): 10 (9 men and 1 woman) in group R had graft rejection (ISHLT >2) in the first biopsy and 29 (22 men and 7 women) in group C were without rejection. Ischemic cardiomyopathy occurred in 2 of 7 and nonischemic cardiomyopathy in 8 of 22 (group R and group C, respectively).

Results: Patients did not differ between groups except diabetes, which occurred more often in group R. Immunosuppressive drug levels were: group R and group C, respectively, 2.13 ± 0.49 and 2.11 ± 0.72 μg/mL; P = .93 for mycophenolate mofetil (MMF) and 9.42 ± 1.76 and 9.63 ± 2.30 ng/mL; P = .75 for tacrolimus. ICU stay was 14 ± 11 vs 15 ± 15 days; P = .76. There were 2 of 6 primary graft failures, 1 of 1 neurologic complications, and 0 of 6 reoperations (P < .05) in group R and group C, respectively. One patient died from group C in 30 days. During the hospital stay the incidence of graft rejection was diagnosed in 20 patients (16men and 4 women) (ISHLT >2 in endomyocardial biopsy) in the study population.

Conclusions: Monitoring of tacrolimus concentration in the early post--heart transplant period does not identify patients with rejection in the authors' study. Monitoring concentration of MMF does not identify patients with rejection. Further investigation is needed to evaluate factors responsible for post--heart transplant rejection in the early phase.

MeSH terms

  • Adult
  • Female
  • Graft Rejection / epidemiology*
  • Graft Rejection / prevention & control
  • Heart Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / blood*
  • Immunosuppressive Agents / pharmacokinetics
  • Incidence
  • Male
  • Middle Aged
  • Mycophenolic Acid / blood*
  • Mycophenolic Acid / pharmacokinetics
  • Retrospective Studies
  • Tacrolimus / blood*
  • Tacrolimus / pharmacokinetics

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus