Higher tacrolimus trough levels and time in the therapeutic range are associated with the risk of acute rejection in the first month after renal transplantation

Thi Van Anh Nguyen; Huu Duy Nguyen; Thi Lien Huong Nguyen; Viet Thang Le; Xuan Kien Nguyen; Viet Tien Tran; Dinh Tuan Le; Ba Thang Ta

doi:10.1186/s12882-023-03188-0

Higher tacrolimus trough levels and time in the therapeutic range are associated with the risk of acute rejection in the first month after renal transplantation

BMC Nephrol. 2023 May 8;24(1):131. doi: 10.1186/s12882-023-03188-0.

Authors

Thi Van Anh Nguyen¹, Huu Duy Nguyen², Thi Lien Huong Nguyen², Viet Thang Le³, Xuan Kien Nguyen⁴, Viet Tien Tran⁵, Dinh Tuan Le⁶, Ba Thang Ta⁷

Affiliations

¹ Department of Pharmacy, 103 Military hospital, 261 Phung Hung, Ha Dong, Hanoi, Vietnam.
² Department of Clinical Pharmacy, Hanoi University of Pharmacy, 13-15 Le Thanh Tong Street, Hanoi, Vietnam.
³ Department of Renal and Haemodialysis, 103 Military hospital, 261 Phung Hung, Ha Dong, Hanoi, Vietnam.
⁴ Department of Military Medical Command and Organization, Vietnam Military Medical University, Hanoi, 10000, Vietnam.
⁵ Department of Infectious Diseases, 103 Military Hospital, 261 Phung Hung, Ha Dong, Hanoi, Vietnam.
⁶ Department of Rheumatology and Endocrinology, 103 Military Hospital, 261 Phung Hung, Ha Dong, Hanoi, Vietnam.
⁷ Respiratory Center, 103 Military hospital, 103 Military Hospital, 261 Phung Hung, Ha Dong, Hanoi, Vietnam.

Abstract

Background: Tacrolimus trough levels (C₀) are used in most transplant centres for therapeutic drug monitoring (TDM) of tacrolimus (Tac). The target range of Tac C₀ has been remarkably changed, with a target as low as 3-7 ng/ml in the 2009 European consensus conference and a target of 4-12 ng/ml (preferably to 7-12 ng/ml) following the second consensus report in 2019. Our aim was to investigate whether reaching early Tac therapeutic targets and maintaining time in the therapeutic range (TTR) according to the new recommendations may be necessary for preventing acute rejection (AR) during the first month after transplantation.

Methods: A retrospective study including 160 adult renal transplant patients (113 men and 47 women) with a median age of 36.3 (20-44) years was conducted between January 2018 and December 2019 at 103 Military Hospital (Vietnam). Tac trough levels were recorded in the first month, and episodes of AR were confirmed by kidney biopsy. Tac TTR was calculated as the percentage of time within the target range of 7-12 ng/ml, according to the 2019 second consensus report. Multivariate Cox analysis was performed to identify the correlation between the Tac target range and TTR with AR.

Results: In the first month after RT, 14 (8.8%) patients experienced AR. There was a significant difference in the incidence of AR between the Tac level groups of < 4, 4-7 and > 7 ng/ml (p = 0.0096). In the multivariate Cox analysis, after adjusting for related factors, a mean Tac level > 7 ng/ml was associated with an 86% decreased risk of AR compared with that of 4-7 ng/ml in the first month (HR, 0.14; 95% CI, 0.03-0.66; p = 0.0131). Every 10% increase in TTR was associated with a 28% lower risk of AR (HR, 0.72; 95% CI, 0.55-0.94; p = 0.014).

Conclusion: Gaining and maintaining Tac C₀ according to the 2019 second consensus report might reduce the risk of AR in the first month following transplantation.

Keywords: Acute rejection; Renal transplantation; Tacrolimus; Therapeutic drug monitoring; Time in therapeutic range; Vietnam.

MeSH terms

Adult
Consensus
Female
Humans
Kidney Transplantation* / adverse effects
Male
Multivariate Analysis
Retrospective Studies
Tacrolimus* / therapeutic use

Substances

Tacrolimus