心脏移植术后早期他克莫司浓度及代谢率与预后的关系

Correlation of tacrolimus concentration and metabolic rate with prognosis in the early stage after heart transplantation

目的评估心脏移植术后早期他克莫司谷浓度(C_(0))、代谢率、变异度与预后的相关性。方法收集2018年4月至2022年12月心脏移植术后30 d内受者的他克莫司谷浓度和服药剂量,计算C_(0)平均值、代谢率(C_(0)/D)及二者变异度,随访受者术后感染、排斥及死亡结局,分析他克莫司早期暴露情况与预后的相关性。结果最终纳入172例心脏移植受者,他克莫司C_(0)平均值、峰值与预后无相关性(均P>0.05)。C_(0)未达治疗目标(<10 ng/mL)组和达标组(10~15 ng/mL)受者在术后感染、排斥及死亡方面差异均无统计学意义(P>0.05)。总体感染、住院感染及因感染再住院的受者C_(0)/D值均明显高于未发生感染的受者,差异有统计学意义(Z=2.720、2.013、2.377,P=0.007、0.044、0.017)。发生住院感染、感染再住院或总体感染的受者C_(0)/D的标准差(SD)值明显高于未发生感染者(Z=2.044、2.432、2.816,P=0.041、0.015、0.005),死亡受者C_(0)/D的SD值也高于存活受者(Z=2.255,P=0.024)。结论他克莫司C_(0)与排斥、总体感染和死亡结局之间未发现统计学相关性;他克莫司慢代谢者较快代谢者更容易出现术后感染;他克莫司代谢率的变异度与不良结局的发生具有相关性。

Objective To evaluate the correlation of tacrolimus trough concentration,metabolic rate and their variability with postoperative infection,rejection and death in the early stage of heart transplantation.Methods The information of recipients who underwent heart transplantation in our hospitalwas reviewed,and the tacrolimus trough concentration(C_(0))monitoring value and tacrolimus dose were collected within 30 days after surgery.The mean C_(0)value,metabolic rate(C_(0)/D)and their variability were calculated.The postoperative infection,rejection and death of recipients were followed up,and the correlation between early exposure of tacrolimus and these prognosis was analyzed.Results A total of 172 heart transplant recipients were finally included as research subjects.The mean and peak value of tacrolimus C_(0)had no statistical correlation with prognosis(all P>0.05).The C_(0)/D values of recipients with overall infection,hospitalized infection and rehospitalization due to infection were significantly higher than those without infection,and the differences were statistically significant(2.044,2.432 and 2.816,P=0.007、0.044 and 0.017,respectively).In terms of rejection and death,there was no statistical difference in C_(0)/D value(P>0.05).The subjects were divided into concentration<10 ng/mL group(n=132),10~15 ng/mL group(n=34)and>15 ng/mL group(n=6),there was no significant difference in postoperative infection,rejection and death(all P>0.05).The SD values of C_(0)/D in recipients with hospitalized infection,infection rehospitalization or overall infection were significantly higher than those without infection(Z=2.044,2.432 and 2.816,P=0.041,0.015 and 0.005,respectively).The SD value of C_(0)/D in death recipients was also higher than that in survival recipients(Z=2.255,P=0.024).Conclusion Tacrolimus C_(0)is not significantly associated with rejection,overall infection,and death;tacrolimus slow metabolizers are more prone to postoperative infection than fast metabolizers;the variability of tacrolimus metabolic rate is related to the incidence of postoperative infection,and the higher variability of meta⁃bolic rate of tacrolimus is a risk factor for poor prognosis after heart transplantation.