| 摘要: |
| 目的:探讨他克莫司治疗儿童肾病综合征的血药谷浓度(C0 ),分析基因多态性及临床指标对他克莫司体内暴露水平的
影响,为临床个体化用药提供依据。方法:回顾性纳入2021 年1 月至2023 年11 月我院收治的64 例首次接受他克莫司治疗的
肾病综合征患儿,收集患儿临床资料、他克莫司血药浓度、CYP3A5∗3 和ABCB1 3435C>T 基因型检测结果及疗效数据。采用受
试者工作特征(ROC)曲线确定最佳疗效C0 阈值,并通过单因素和多元线性回归分析筛选影响他克莫司标准化血药浓度(C0 / D)
的独立因素。结果:治疗1 个月后患儿总缓解率84.9%,初始C0 达标率仅15.63%,剂量调整后升至62.07%。8 例未缓解患儿的初始
C0 均未达标,1 个月后仅1 例达标。ROC 曲线分析显示,他克莫司C0 最佳疗效阈值为4.55 ng/ mL(AUC=0.719, P=0.048)。CYP3A5∗
3/ ∗3 型、ABCB1 3435C>T TT 型患儿的C0 / D 高于其他分型(P<0. 01)。多元回归分析证实体质量是影响C0 / D 的独立因素
(β =1. 986,P<0. 001),体质量越大,C0 / D 越高。结论:他克莫司治疗儿童肾病综合征疗效确切,C0 达到4. 55 ng/ mL 可作为实
现临床缓解的参考阈值。CYP3A5∗3、ABCB1 3435C>T 基因多态性及体质量是影响他克莫司血药浓度的重要因素,临床可结合
上述指标制定个体化初始剂量并动态监测血药浓度。 |
| 关键词: 他克莫司 儿童 肾病综合征 血药浓度 基因多态性 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2026.11.007 |
|
| 基金项目:基金项目:河南省医学科技攻关计划联合共建项目,编号LHGJ20250589。 |
|
| Influencing Factors of Tacrolimus Blood Concentration in Children with Nephrotic Syndrome and RelevantEfficacy Thresholds |
| Chang Zhao, Zhou Yuxue, Zhang Shengnan, Lyu Meng |
| (Children’ s Hospital Affiliated to Zhengzhou University, Henan
Children’s Hospital Zhengzhou Children’s Hospital, Zhengzhou 450018, China) |
| Abstract: |
| Objective: To probe into blood trough concentration (C0 ) of tacrolimus in children with nephrotic syndrome, and to analyze
the effects of genetic polymorphisms and clinical indicators on the intracellular exposure level of tacrolimus, so as to provide basis for
individualized medication in clinical practice. Methods: A retrospective study was performed on 64 children with nephrotic syndrome
receiving initial Tac from Jan. 2021 to Nov. 2023. Clinical data, C0 of tacrolimus, CYP3A5∗3 and ABCB1 3435C>T genotypes, and
efficacy were collected. The optimal C0 threshold was determined by receiver operating characteristic (ROC) curve, and independent
factors affecting standardized concentration (C0 / D) were screened by multivariate linear regression. Results: The one-month total
remission rate was 84. 9%. Initial C0 target attainment rate was 15. 63%, rising to 62. 07% after dose adjustment. The initial C0 for 8
children who were not in remission did not meet the standard, only one achieved the standard after one month. The ROC curve analysis
revealed that optimal C0 threshold was 4. 55 ng/ mL (AUC = 0. 719, P = 0. 048). The C0 / D of children with CYP3A5∗3/ ∗3 and
ABCB1 3435C>T TT genotypes were higher than those of other genotypes (P<0. 01). Multivariate regression analysis confirmed that
body weight was an independent factor affecting C0 / D (β =1. 986, P<0. 001), and the greater the body weight, the higher the C0 / D.
Conclusion: Tacrolimus is effective in the treatment of children with nephrotic syndrome, and C0 of 4. 55 ng/ mL can be used as a
reference threshold for clinical remission. The CYP3A5 ∗3/ ∗3 and ABCB1 3435C > T gene polymorphisms and body weight are
important factors influencing the blood concentration of tacrolimus. Clinically, individualized initial doses can be determined based on
these indicators, and the blood concentration can be dynamically monitored. |
| Key words: tacrolimus children nephrotic syndrome blood concentration gene polymorphism |
