Tacrolimus trough levels higher than 6 ng/mL might not be required after a year in stable kidney transplant recipients

PLoS One. 2020 Jul 2;15(7):e0235418. doi: 10.1371/journal.pone.0235418. eCollection 2020.

Abstract

Background: Little is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs.

Methods: KTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections.

Results: A total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups.

Conclusions: TAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.

Publication types

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

MeSH terms

  • Adult
  • Cardiovascular Diseases / chemically induced
  • Cohort Studies
  • Cytomegalovirus Infections / chemically induced
  • Female
  • Graft Rejection / chemically induced
  • Humans
  • Immunosuppression Therapy / adverse effects*
  • Immunosuppressive Agents* / administration & dosage
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / blood
  • Kidney Transplantation / rehabilitation*
  • Male
  • Middle Aged
  • Opportunistic Infections / chemically induced
  • Polyomavirus Infections / chemically induced
  • Renal Insufficiency / chemically induced
  • Republic of Korea
  • Tacrolimus* / administration & dosage
  • Tacrolimus* / adverse effects
  • Tacrolimus* / blood

Substances

  • Immunosuppressive Agents
  • Tacrolimus

Grants and funding

This research was supported by the Research Program funded by the Korea Centers for Disease Control and Prevention (No. 2012E3301100, 2013E3301600, 2013E3301601, 2013E3301602, 2016E3300200, 2016E3300201, 2016E3300202, and 2019E320100) to CA and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, which is funded by the Ministry of Health & Welfare, Republic of Korea (No. HI13C1232) to CDK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.