Analysis of reference range and influencing factors of tacrolimus blood concentration in children with Henoch-Schonlein purpura nephritis

LI Huiying; LI Fashuang; LI Linbo; ZHANG Lilin

doi:10.6039/j.issn.1001-0408.2025.08.15

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Analysis of reference range and influencing factors of tacrolimus blood concentration in children with Henoch-Schonlein purpura nephritis

更新时间：2025-09-23

- Analysis of reference range and influencing factors of tacrolimus blood concentration in children with Henoch-Schonlein purpura nephritis
- ZHONGGUO YAOFANG Vol. 36, Issue 8, Pages: 975-980(2025)
- 作者机构：
  
  昆明医科大学附属儿童医院药学部，昆明　650228
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.08.15
  CLC： R985;R692.3+4
- Received：04 November 2024，
  
  Revised：2025-03-02，
  
  Accepted：28 March 2025，
  
  Published：30 April 2025
- 稿件说明：
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李惠英,李发双,黎林波,等.过敏性紫癜性肾炎患儿他克莫司血药浓度参考范围及影响因素分析 [J].中国药房,2025,36(08):975-980.

LI Huiying,LI Fashuang,LI Linbo,et al.Analysis of reference range and influencing factors of tacrolimus blood concentration in children with Henoch-Schonlein purpura nephritis[J].ZHONGGUO YAOFANG,2025,36(08):975-980.
李惠英,李发双,黎林波,等.过敏性紫癜性肾炎患儿他克莫司血药浓度参考范围及影响因素分析 [J].中国药房,2025,36(08):975-980. DOI： 10.6039/j.issn.1001-0408.2025.08.15.

LI Huiying,LI Fashuang,LI Linbo,et al.Analysis of reference range and influencing factors of tacrolimus blood concentration in children with Henoch-Schonlein purpura nephritis[J].ZHONGGUO YAOFANG,2025,36(08):975-980. DOI： 10.6039/j.issn.1001-0408.2025.08.15.

摘要

目的

探讨他克莫司在过敏性紫癜性肾炎（HSPN）患儿中的血药浓度参考范围，并分析他克莫司血药浓度的影响因素，为临床合理使用该药提供参考。

方法

回顾性收集2018年1月至2024年1月就诊于昆明医科大学附属儿童医院使用他克莫司治疗并定期进行血药浓度监测的HSPN患儿的临床资料，通过受试者工作特征曲线确定他克莫司血药浓度的有效临界值，对比他克莫司不同浓度的临床疗效和不良反应发生率以确定他克莫司血药浓度参考范围。采用单因素和多元线性回归分析他克莫司血药浓度的影响因素。

结果

纳入97例患儿，共监测他克莫司血药浓度203次，测得血药浓度为4.26（2.47，6.34）ng/mL。受试者工作特征曲线下面积为0.723（95%CI为0.596～0.850，

＜0.01），对应的血药浓度有效临界值为2.19 ng/mL。他克莫司血药浓度3～＜5 ng/mL、5～＜10 ng/mL、≥10 ng/mL组患儿的临床疗效均显著高于＜3 ng/mL组（

＜0.05），5～＜10 ng/mL、≥10 ng/mL组患儿总不良反应发生率均显著高于＜3 ng/mL、3～＜5 ng/mL组（

＜0.05）。体重指数和

CYP3A5

基因型对他克莫司血药浓度的影响具有统计学意义（

＜0.05）。

结论

临床应用他克莫司治疗HSPN患儿时，血药浓度参考范围为3～5 ng/mL；体重指数和

CYP3A5

基因型是他克莫司血药浓度的影响因素。

Abstract

OBJECTIVE

To investigate the reference range of tacrolimus blood concentration in children with Henoch-Schonlein purpura nephritis （HSPN） and analyze the factors affecting the blood concentration， in order to provide a reference for rational use of the drug in clinic.

METHODS

Clinical data of children with HSPN who were treated with tacrolimus and regularly monitored for blood concentration at the Children’s Hospital Affiliated to Kunming Medical University were retrospectively collected from January 2018 to January 2024. The threshold of effective concentration of tacrolimus was determined by the receiver operating characteristic curve of the subjects. The clinical efficacy of tacrolimus in different concentrations and the incidence of adverse drug reaction （ADR） were compared to determine the reference range of tacrolimus blood concentration. The factors influencing the blood concentration were analyzed by one-way and multiple linear regression.

RESULTS

A total of 97 pediatric patients were included， and their tacrolimus blood concentrations were monitored 203 times， the blood concentration was 4.26 （2.47， 6.34） ng/mL. The area under the receiver operating characteristic curve of the subjects was 0.723 （95%CI：0.596-0.850，

＜0.01）， which corresponded to an effective threshold of 2.19 ng/mL. The clinical efficacy in pediatric patients with tacrolimus blood concentrations of 3-＜5 ng/mL， 5-＜10 ng/mL， and ≥10 ng/mL was significantly higher than that of children with concentrations ＜3 ng/mL （

＜0.05）. Additionally， the overall incidence of ADR in children with concentrations of 5-＜10 ng/mL and ≥10 ng/mL was significantly higher than that in children with concentrations ＜3 ng/mL and 3-＜5 ng/mL （

＜0.05）. The impact of body mass index and

CYP3A5

genotype on the blood concentration of tacrolimus was statistically significant （

＜0.05）.

CONCLUSIONS

When using tacrolimus to treat HSPN in children clinically， the reference range for blood concentration is 3 to 5 ng/mL； body mass index and

CYP3A5

genotype are factors that influence the blood concentration of tacrolimus.

关键词

Keywords

references

TANG Y ， CHEN W T ， LI J P ， et al . A disease-targeted picture book for children with Henoch-Schonlein purpura nephritis：a quasi-experimental study [J ] . J Ren Care ， 2023 ， 49 （ 4 ）： 243 - 252 .

SU Q X ， JIANG L J ， CHAI J ， et al . Changes of peripheral blood lymphocyte subsets and immune function in children with Henoch-Schonlein purpura nephritis [J ] . Iran J Immunol ， 2021 ， 18 （ 3 ）： 259 - 267 .

CATTRAN D C ， FEEHALLY J ， COOK H T ， et al . Kidney Disease：Improving Global Outcomes（KDIGO） glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis [J ] . Kidney Int ， 2012 ， 2 （ 2 ）： 139 - 274 .

GAN Y H ， CHEN J H ， WANG M ， et al . The efficacy and safety of tacrolimus in treating refractory IgA vasculitis nephritis：a single-center retrospective study on 16 cases [J ] . Clin Kidney J ， 2024 ， 17 （ 5 ）： sfae115 .

WU D Y ， MA R ， WANG X M ， et al . Efficacy and safety of tacrolimus in the treatment of pediatric Henoch-Schönlein purpura nephritis [J ] . Paediatr Drugs ， 2022 ， 24 （ 4 ）： 389 - 401 .

VIVARELLI M ， SAMUEL S ， COPPO R ， et al . IPNA clinical practice recommendations for the diagnosis and management of children with IgA nephropathy and IgA vasculitis nephritis [J ] . Pediatr Nephrol ， 2025 ， 40 （ 2 ）： 533 - 569 .

ZHANG Y D ， SHEN B W ， LI Y ， et al . Drug-drug interaction between tacrolimus and caspofungin in Chinese kidney transplant patients with different CYP3A5 genotypes [J ] . Ther Adv Drug Saf ， 2024 ， 15 ： 20420986241243165 .

NGUYEN T V A ， LE B H ， NGUYEN M T ， et al . Pharmacogenomic analysis of CYP3A5*3 and tacrolimus trough concentrations in Vietnamese renal transplant outcomes [J ] . Pharmgenomics Pers Med ， 2024 ， 17 ： 53 - 64 .

DU Y ， ZHANG Y D ， YANG Z Y ， et al . Artificial neural network analysis of determinants of tacrolimus pharmacokinetics in liver transplant recipients [J ] . Ann Pharmacother ， 2024 ， 58 （ 5 ）： 469 - 479 .

杨帆，蒋小云 . 儿童激素敏感、复发/依赖肾病综合征诊治循证指南（2016）解读 [J ] . 中华儿科杂志， 2017 ， 55 （ 10 ）： 738 - 742 .

李发双，黎林波，李惠英，等 . 他克莫司血药浓度监测超高效液相色谱法的建立及个体化临床分析应用 [J ] . 中国医院药学杂志， 2024 ， 44 （ 22 ）： 2581 - 2585 .

中华医学会儿科学分会肾脏病学组 . 儿童常见肾脏疾病诊治循证指南（二）：紫癜性肾炎的诊治循证指南（试行） [J ] . 中华儿科杂志， 2009 ， 47 （ 12 ）： 911 - 913 .

ABU-ZAID M H ， SALAH S ， LOTFY H M ， et al . Consensus evidence-based recommendations for treat-to-target management of immunoglobulin A vasculitis [J ] . Ther Adv Musculoskelet Dis ， 2021 ， 13 ： 1759720 X 211059610 .

WANG J J ， MAO J H ， CHEN J Y ， et al . Evaluation of mycophenolate mofetil or tacrolimus in children with steroid sensitive but frequently relapsing or steroid-dependent nephrotic syndrome [J ] . Nephrology（Carlton）， 2016 ， 21 （ 1 ）： 21 - 27 .

BASU B ， SANDER A ， ROY B ， et al . Efficacy of ritu-ximab vs tacrolimus in pediatric corticosteroid-dependent nephrotic syndrome：a randomized clinical trial [J ] . JAMA Pediatr ， 2018 ， 172 （ 8 ）： 757 - 764 .

黄松明 . 儿童健康好帮手：儿童泌尿系统疾病分册 [M ] ．北京：人民卫生出版社， 2013 ： 327 - 328 ．

WANG H ， LIU M C ， WANG X W ， et al . Optimal trough concentration of tacrolimus in pediatric patients with primary nephrotic syndrome [J ] . Clin Pharmacol Ther ， 2025 ， 117 （ 2 ）： 436 - 444 .

ZHAO W ， ZHANG D F ， HAO G X ， et al . Off-label use of tacrolimus in children with Henoch-Schonlein purpura nephritis：efficacy and safety [J ] . Arch Dis Child ， 2017 ， 102 （ 10 ）： 47 - 49 .

WU Z S ， MENG Q Y ， XIA Y X ， et al . A retrospective analysis of the safety and efficacy of low dose tacrolimus（FK506）for living donor liver transplant recipients [J ] . J Biomed Res ， 2013 ， 27 （ 4 ）： 305 - 309 .

GUO H L ， XU J ， SUN J Y ， et al . Tacrolimus treatment in childhood refractory nephrotic syndrome：a retrospective study on efficacy，therapeutic drug monitoring，and contributing factors to variable blood tacrolimus levels [J ] . Int Immunopharmacol ， 2020 ， 81 ： 106290 .

CHEN H X ， CHENG Q ， LI F ， et al . Efficacy and safety of tacrolimus and low-dose prednisone in Chinese children with steroid-resistant nephrotic syndrome [J ] . World J Pediatr ， 2020 ， 16 （ 2 ）： 159 - 167 .

TRAUTMANN A ， VIVARELLI M ， SAMUEL S ， et al . IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome [J ] . Pediatr Nephrol ， 2020 ， 35 （ 8 ）： 1529 - 1561 .

ZHANG D F ， HAO G X ， LI C Z ， et al . Off-label use of tacrolimus in children with Henoch-Schönlein purpura nephritis：a pilot study [J ] . Arch Dis Child ， 2018 ， 103 （ 8 ）： 772 - 775 .

CHAUHAN P M ， HEMANI R J ， SOLANKI N D ， et al . A systematic review and meta-analysis recite the efficacy of tacrolimus treatment in renal transplant patients in association with genetic variants of CYP3A5 gene [J ] . Am J Clin Exp Urol ， 2023 ， 11 （ 4 ）： 275 - 292 .

LARGEAU B ， GUELLEC C B ， LONGUET H ， et al . Comparison of tacrolimus starting doses based on CYP3A5 phenotype or genotype in kidney transplant recipients [J ] . Prog Transplant ， 2019 ， 29 （ 4 ）： 300 - 308 .

KHAMLEK K ， KOMENKUL V ， SRIBOONRUANG T ， et al . Population pharmacokinetic models of tacrolimus in pediatric solid organ transplant recipients：a systematic review [J ] . Br J Clin Pharmacol ， 2024 ， 90 （ 2 ）： 406 - 426 .

MARUYAMA Y ， MAEJIMA Y ， HIRABAYASHI K ， et al . Factors affecting day-to-day variations in tacrolimus concentration among children and young adults undergoing allogeneic hematopoietic stem cell transplantation [J ] . Transplant Cell Ther ， 2023 ， 29 （ 4 ）： 270.e1 - 270.e8 .

PASTERNAK A L ， PARK J M ， PAI M P . Predictive capa-city of population pharmacokinetic models for the tacrolimus dose requirements of pediatric solid organ transplant recipients [J ] . Ther Drug Monit ， 2023 ， 45 （ 1 ）： 95 - 101 .

周艳，周波，吕凤俊，等 . 儿童肾病综合征患者他克莫司血药浓度影响因素分析 [J ] . 中国新药杂志， 2019 ， 28 （ 18 ）： 2299 - 2304 .

朱丽丽，王轶睿，韩罡，等 . 104例不同民族肾病综合征患者他克莫司血药浓度的影响因素分析 [J ] . 中国药房， 2019 ， 30 （ 15 ）： 2110 - 2114 .

SURESH P K ， VENKATACHALAPATHY Y ， EKAMBARAM S ， et al . Cytochrome P450 3A gene family and medication in childhood nephrotic syndrome：an update [J ] . Glob Med Genet ， 2024 ， 12 （ 1 ）： 100009 .

RANČIĆ N ， DRAGOJEVIĆ-SIMIĆ V ， VAVIĆ N ， et al . Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy：the influence of gender and comedication [J ] . Vojnosanit Pregl ， 2015 ， 72 （ 9 ）： 813 - 822 .

HUANG S Q ， SONG W ， JIANG S M ， et al . Pharmacokinetic interactions between tacrolimus and Wuzhi capsule in liver transplant recipients：genetic polymorphisms affect the drug interaction [J ] . Chem Biol Interact ， 2024 ， 391 ： 110906 .

QU J L ， BIAN R R ， LIU B G ， et al . The pharmacokinetic study of tacrolimus and Wuzhi capsule in Chinese liver transplant patients [J ] . Front Pharmacol ， 2022 ， 13 ： 956166 .

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