Intrapatient Variability in Tacrolimus Trough Levels Over 2 Years Affects Long-Term Allograft Outcomes of Kidney Transplantation

• Published in: Frontiers in immunology 2021-09, Vol.12, p.746013-746013
• Main Authors: Park, Yohan, Lee, Hanbi, Eum, Sang Hun, Kim, Hyung Duk, Ko, Eun Jeong, Yang, Chul Woo, Chung, Byung Ha
• Format: Article
• Language: English
• Subjects: Adult; allograft; Allografts; Biological Variation, Individual; Biopsy; Female; Follow-Up Studies; Graft Rejection - epidemiology; Graft Rejection - prevention & control; graft survival; Graft Survival - drug effects; Humans; Immunology; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Kaplan-Meier Estimate; Kidney Transplantation; Male; Middle Aged; Proportional Hazards Models; rejection; Retrospective Studies; tacrolimus; Tacrolimus - blood; Tacrolimus - pharmacokinetics; Tacrolimus - therapeutic use; transplant; Treatment Outcome
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.746013

This study aimed to determine the impact of tacrolimus (TAC) trough level (C0) intrapatient variability (IPV) over a period of 2 years after kidney transplantation (KT) on allograft outcomes. In total, 1,143 patients with low immunologic risk were enrolled. The time-weighted coefficient variability (TWCV) of TAC-C0 was calculated, and patients were divided into tertile groups (T1: < 24.6%, T2: 24.6%-33.7%, T3: ≥ 33.7%) according to TAC-C0-TWCV up to post-transplant 1 year. They were classified into the low/low, low/high, high/low, and high/high groups based on a TAC-C0-TWCV value of 33.7% during post-transplant 0-1 and 1 -2 years. The allograft outcomes among the three tertile and four TAC-C0-TWCV groups were compared. The T3 group had the highest rate of death-censored allograft loss (DCGL), and T3 was considered an independent risk factor for DCGL. The low/low group had the lowest and the high/high group had the highest risk for DCGL. Moreover, patients with a mean TAC-C0 of ≥5 ng/ml in the high/high group were at the highest risk for DCGL. Thus, TAC-IPV can significantly affect allograft outcomes even with a high mean TAC-C0. Furthermore, to improve allograft outcomes, a low TAC-IPV should be maintained even after the first year of KT.