奈玛特韦/利托那韦治疗下肾移植受者他克莫司谷浓度个体内变异度及其对血清肌酐的影响

Intrapatient variability of tacrolimus trough concentrations and its effect on serum creatinine level in kidney transplant recipients treated with nematvir/ritonavir

目的探讨奈玛特韦/利托那韦治疗下肾移植受者他克莫司谷浓度个体内变异度(IPV)情况及其对血清肌酐(Scr)的影响。方法收集41例使用奈玛特韦/利托那韦治疗新型冠状病毒感染的肾移植受者的临床资料,总结奈玛特韦/利托那韦与他克莫司使用情况,分析他克莫司谷浓度分布情况及目标浓度达标率,以及他克莫司谷浓度的IPV分布及其与Scr变化的相关性。结果41例肾移植受者中,足量和低剂量使用奈玛特韦/利托那韦的各占46%(19/41),高剂量使用奈玛特韦/利托那韦的占7%(3/41)。95%(39/41)的患者在使用奈玛特韦/利托那韦前24 h停用他克莫司,5%(2/41)的患者在使用奈玛特韦/利托那韦后24 h停用他克莫司;所有患者在奈玛特韦/利托那韦5 d疗程结束至少3 d后开始重新启用他克莫司。服药前、服药期间、停药1周、停药2周、停药1个月他克莫司谷浓度达标率分别为73%(30/41)、30%(3/10)、48%(15/31)、35%(11/31)、53%(16/30)。IPV中位数为35%(23%,51%),Spearman相关性分析结果显示,受者的Scr升高倍数与IPV呈正相关(rs=0.4007,P=0.0282)。结论奈玛特韦/利托那韦治疗下肾移植受者他克莫司谷浓度达标率降低,他克莫司谷浓度的IPV升高,且IPV较高的受者更容易引起Scr升高。

Objective To investigate the intra-patient variability(IPV)of tacrolimus trough concentrations and its effect on serum creatinine(Scr)level in kidney transplant recipients treated with nematvir/ritonavir.Methods Clinical data of 41 kidney transplant recipients infected by SARS-CoV-2 and treated with nematvir/ritonavir were collected.The usage of nematvir/ritonavir and tacrolimus was summarized.The distribution of tacrolimus trough concentrations and the attainment rate of target concentration were analyzed.The correlation between the IPV distribution of tacrolimus trough concentrations and the changes of Scr level was determined.Results Among 41 kidney transplant recipients,46%(19/41)were given with full-and low-dose nematvir/ritonavir,and 7%(3/41)were given with high-dose nematvir/ritonavir.Use of tacrolimus was discontinued at 24 h before nematvir/ritonavir treatment in 95%(39/41)patients,and at 24 h after use of nematvir/ritonavir in 5%(2/41)patients.Tacrolimus was given at least 3 d after the 5-d course of nematvir/ritonavir in all patients.The attainment rate of tacrolimus trough concentration was 73%(30/41),30%(3/10),48%(15/31),35%(11/31)and 53%(16/30)before,during,1 week,2 weeks and 1 month after use of nematvir/ritonavir,respectively.The median IPV was 35%(23%,51%).Spearman correlation analysis showed that the increase of Scr level was positively correlated with IPV(rs=0.4007,P=0.0282).Conclusions The attainment rate of tacrolimus trough concentration is declined in kidney transplant recipients treated with nematvir/ritonavir.The IPV of tacrolimus trough concentrations is elevated.The recipients with higher IPV are prone to an elevation in Scr level.