Drug design, development and therapy · 2025
Impact of High Tacrolimus Exposure on Graft Function and Development of a Prediction Model in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.
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Yang Wenyu, Xia Renfei, Zhao Peijin, Du Juanhua, Liu Rumin, Zeng Wenli, Chen Yan, Luo Xin, Zheng Ping, Li Yilei, Mo Liqian
Аннотация
PURPOSE: To evaluate the association between early supratherapeutic tacrolimus exposure (trough concentration >20 ng/mL within the first postoperative week) and graft outcomes in kidney transplant recipients, and to develop a prediction model for this early high exposure.
PATIENTS AND METHODS: This single-center retrospective cohort study included 210 kidney transplant recipients (105 exposed, 105 non-exposed) after propensity score matching. Renal function (eGFR, cystatin C) and infection rates over the first year were compared using linear mixed-effects models with multiple imputation. A Cox proportional hazards model with LASSO variable selection was developed to predict the risk of high exposure.
RESULTS: The exposed group had significantly lower eGFR at 7 days, 1, and 3 months (adjusted mean differences: -11.32, -10.20, -10.75 mL/min/1.73 m2) and higher cystatin C (0.83, 0.36, 0.36 mg/L). At 1 year, eGFR remained lower (-7.54 mL/min/1.73 m2, P=0.038) and cystatin C higher (0.40 mg/L, P=0.043) in the exposed group. The 1-year infection rate was higher in the exposed group (80.0% vs 52.3%; adjusted OR=4.27, P<0.001). The prediction model identified CYP3A5 *3/*3 genotype (HR=2.19), elevated C-reactive protein on day 1 (HR=1.27), and higher weight-adjusted tacrolimus dose (HR=1.58) as key predictors (C-index=0.716; optimism-corrected C-index=0.728).
CONCLUSION: Early high tacrolimus exposure is associated with impaired renal function and increased infection risk in the first year after transplantation. A prediction model incorporating genetic, inflammatory, and dosing factors could aid in early risk stratification.
PATIENTS AND METHODS: This single-center retrospective cohort study included 210 kidney transplant recipients (105 exposed, 105 non-exposed) after propensity score matching. Renal function (eGFR, cystatin C) and infection rates over the first year were compared using linear mixed-effects models with multiple imputation. A Cox proportional hazards model with LASSO variable selection was developed to predict the risk of high exposure.
RESULTS: The exposed group had significantly lower eGFR at 7 days, 1, and 3 months (adjusted mean differences: -11.32, -10.20, -10.75 mL/min/1.73 m2) and higher cystatin C (0.83, 0.36, 0.36 mg/L). At 1 year, eGFR remained lower (-7.54 mL/min/1.73 m2, P=0.038) and cystatin C higher (0.40 mg/L, P=0.043) in the exposed group. The 1-year infection rate was higher in the exposed group (80.0% vs 52.3%; adjusted OR=4.27, P<0.001). The prediction model identified CYP3A5 *3/*3 genotype (HR=2.19), elevated C-reactive protein on day 1 (HR=1.27), and higher weight-adjusted tacrolimus dose (HR=1.58) as key predictors (C-index=0.716; optimism-corrected C-index=0.728).
CONCLUSION: Early high tacrolimus exposure is associated with impaired renal function and increased infection risk in the first year after transplantation. A prediction model incorporating genetic, inflammatory, and dosing factors could aid in early risk stratification.