European journal of pharmacology · 2025
The impact of high intrapatient variability of tacrolimus in peripheral blood mononuclear cells on the outcomes of kidney transplantation.
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Xu Huan, Dai Xinhua, Wang Xueqiao, Yue Jiaxi, Gong Xingxin, Bai Yangjuan, Yan Lin, Li Yamei, Li Yi
Аннотация
BACKGROUND: Tacrolimus (TAC) is a key immunosuppressive agent for kidney transplantation, but its narrow therapeutic window and high intra-patient variability (IPV) complicate therapeutic drug monitoring. The clinical significance of PBMC-based IPV in predicting graft rejection and infection remains unclear.
METHODS: A total of 47 renal transplant recipients were enrolled. Intracellular TAC concentrations were analyzed and quantified using liquid chromatography-tandem mass spectrometry. The primary endpoint was the occurrence of the first adverse event, including acute rejection or infection of any etiology. The IPV of peripheral blood mononuclear cells (IPVPBMC) and whole blood (IPVWB) was calculated as the coefficient of variation of dose-corrected concentrations from day 14 to month 12 post-transplantation. A Cox proportional hazards model was employed to identify risk factors associated with kidney transplant outcomes.
RESULTS: Within the first year post-transplantation, the incidence of acute rejection was significantly higher in the High-IPVWB group compared to the Low-IPVWB group (P = 0.024). Moreover, the IPVWB in the rejection group was significantly higher than in the stable group (P = 0.034), and High-IPVWB and extended post-operative hospital stay served as independent predictors of rejection within the first year. Additionally, High-IPVPBMC, deceased donors, and longer hospital stay were the main risk factors for early infection following transplantation.
CONCLUSIONS: Both IPVPBMC and IPVWB are significantly associated with graft rejection and infection. Monitoring IPVPBMC and IPVWB within the first six months post-transplantation could help identify high-risk patients and improve clinical management strategies.
METHODS: A total of 47 renal transplant recipients were enrolled. Intracellular TAC concentrations were analyzed and quantified using liquid chromatography-tandem mass spectrometry. The primary endpoint was the occurrence of the first adverse event, including acute rejection or infection of any etiology. The IPV of peripheral blood mononuclear cells (IPVPBMC) and whole blood (IPVWB) was calculated as the coefficient of variation of dose-corrected concentrations from day 14 to month 12 post-transplantation. A Cox proportional hazards model was employed to identify risk factors associated with kidney transplant outcomes.
RESULTS: Within the first year post-transplantation, the incidence of acute rejection was significantly higher in the High-IPVWB group compared to the Low-IPVWB group (P = 0.024). Moreover, the IPVWB in the rejection group was significantly higher than in the stable group (P = 0.034), and High-IPVWB and extended post-operative hospital stay served as independent predictors of rejection within the first year. Additionally, High-IPVPBMC, deceased donors, and longer hospital stay were the main risk factors for early infection following transplantation.
CONCLUSIONS: Both IPVPBMC and IPVWB are significantly associated with graft rejection and infection. Monitoring IPVPBMC and IPVWB within the first six months post-transplantation could help identify high-risk patients and improve clinical management strategies.