INTRODUCTION AND OBJECTIVES: Chronic allograft injury is a multi-factorial process based on immunologic and non-immunologic factors. Patients with the CYP3A5*3/*3 genotype (non-expressers) require a lower daily tacrolimus dose than those with the CYP3A5*1 allele (expressers) in order to maintain target trough levels. Recently, we reported that IF from 0-hour to 1-year post-transplantation increased more in non-expressers than in expressers with a higher target trough strategy of tacrolimus. Unexpected highly tacrolimus levels in non-expressers might influence the development of IF, despite therapeutic drug monitoring. The present study investigated the increase in IF from 0-hour to 1-year post-transplantation and calculated the risk of developing IF based on clinical characteristics under a lower target strategy of tacrolimus.
METHODS: 96 adult patients receiving living allograft underwent protocol biopsies at 0-hour and 1-year post-transplantation. The blood trough target level of tacrolimus was 15-20 ng/ml within the first, and tapered to less than 8 ng/ml after the fourth week. Quantitative analysis of renal cortical IF was performed using computer-assisted analysis of tissue sections stained with Masson-trichrome. The percentage of IF (%IF) in the allograft cortical region at 0-hour was defined as the baseline, and we calculated the increases in %IF at 1 year. Characteristics of the donor and recipient, clinical events, target trough levels of tacrolimus, CYP3A5 polymorphism, and laboratory data were calculated as risk factors.
RESULTS: The mean %IF at 0-hour and 1-year was 11.8±5.3 % and 14.6±6.1 %, respectively. The mean increase in %IF from 0-hour to 1-year was 1.38±0.74. The %IF at 0-hour and 1-year was significantly higher in donors over 60 year-old. The %IF at 0-hour was also higher in donors with eGFR less than 88 ml/min/1.73m2. Although trough levels of tacrolimus were higher in non-expressers than expressers in the study period, we failed to find any clinical and CYP3A5 genomic factors influenced increased %IF.
CONCLUSIONS: The results suggested a lower target trough level of tacrolimus would not influence the development of IF regardless of CYP3A5 polymorphism and graft survival.
To cite this abstract in AMA style:Komine N, Satoh S, Numakura K, Saito M, Inoue T, Narita S, Miura Y, Tsuchiya N, Kagaya H, Miura M, Habuchi T. Lack of Clinical Factors Increasing Quantitative Interstitial Fibrosis after Renal Transplantation under a Lower Target Trough Strategy of Tacrolimus [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/lack-of-clinical-factors-increasing-quantitative-interstitial-fibrosis-after-renal-transplantation-under-a-lower-target-trough-strategy-of-tacrolimus/. Accessed January 16, 2018.
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