AUTHOR=Song Turun , Yin Saifu , Jiang Yamei , Huang Zhongli , Liu Jinpeng , Wang Zhiling , Li Linde , Zeng Jun , Fan Yu , Wang Xianding , Li Xingxing , Lin Tao 

TITLE=Increasing Time in Therapeutic Range of Tacrolimus in the First Year Predicts Better Outcomes in Living-Donor Kidney Transplantation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02912

DOI=10.3389/fimmu.2019.02912

ISSN=1664-3224

ABSTRACT=Background
The aim of the present study is to investigate the impact of time in therapeutic range TTR on long-term outcomes of living kidney transplants.
Methods
We included 1241 living kidney transplants and randomized them into development and validation cohort with a ratio of 2:1. The tacrolimus TTR percentage was calculated by linear interpolation with target range (5-10 ng/ml months 0-3, 4-8 ng/ml months 4-12). The optimal TTR cutoff was estimated by the receiver operating characteristic curve analysis on the basis of 12 months acute rejection (AR) in development cohort. Outcomes were analyzed between patients with high TTR and low TTR in the development and validation cohort. TTR was also compared with other tacrolimus measures.
Results 
The optimal TTR cutoff value was 78%. In the development cohort, patients with TTR>78% had a significantly higher rejection- and infection-free survival. TTR<78% was an independent risk factor for AR (OR:2.97, 95%CI:1.82-4.84) and infection (OR:1.55, 95%CI:1.08-2.22). Patient and graft survival were significantly higher in those with TTR>78%, and TTR<78% was associated with graft loss (OR:3.2, 95%CI:1.38-7.42) and patient death (OR:6.54, 95%CI:1.34-31.77). These findings were confirmed in the validation cohort. Furthermore, we divided all included patients into high and low TTR group. TTR was more strongly associated with patient and graft survival than mean level, standard deviation and intrapatient variability (IPV).   
Conclusions
Increasing TTR of tacrolimus in the first year was associated with improved long-term outcomes in living kidney transplants, and TTR may be a novel valuable strategy to monitor tacrolimus exposure.