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基于药物基因组学的个性化用药及儿童IgA血管炎肾炎的治疗进展

Individualized medication based on pharmacogenomics and treatment progress in children with IgAV nephritis.

作者信息

Yang Xuerong, Li Qi, He Yuanyuan, Zhu Yulian, Yang Rou, Zhu Xiaoshi, Zheng Xi, Xiong Wei, Yang Yong

机构信息

Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

出版信息

Front Pharmacol. 2022 Jul 22;13:956397. doi: 10.3389/fphar.2022.956397. eCollection 2022.

Abstract

Immunoglobulin A vasculitis (IgAV) nephritis, also known as Henoch-Schönlein purpura nephritis (HSPN), is a condition in which small blood vessel inflammation and perivascular IgA deposition in the kidney caused by neutrophil activation, which more often leads to chronic kidney disease and accounts for 1%-2% of children with end-stage renal disease (ESRD). The treatment principles recommended by the current management guidelines include general drug treatment, support measures and prevention of sequelae, among which the therapeutic drugs include corticosteroids, immunosuppressive agents and angiotensin system inhibitors. However, the concentration range of immunosuppressive therapy is narrow and the individualized difference is large, and the use of corticosteroids does not seem to improve the persistent nephropathy and prognosis of children with IgAV. Therefore, individualized maintenance treatment of the disease and stable renal prognosis are still difficult problems. Genetic information helps to predict drug response in advance. It has been proved that most gene polymorphisms of cytochrome oxidase P450 and drug transporter can affect drug efficacy and adverse reactions (ADR). Drug therapy based on genetics and pharmacogenomics is beneficial to providing safer and more effective treatment for children. Based on the pathogenesis of IgAV, this paper summarizes the current therapeutic drugs, explores potential therapeutic drugs, and focuses on the therapeutic significance of corticosteroids and immunosuppressants in children with IgAV nephritis at the level of pharmacogenomics. In addition, the individualized application of corticosteroids and immunosuppressants in children with different genotypes was analyzed, in order to provide a more comprehensive reference for the individualized treatment of IgAV nephritis in children.

摘要

免疫球蛋白A血管炎(IgAV)肾炎,也称为过敏性紫癜肾炎(HSPN),是一种由中性粒细胞活化引起的肾脏小血管炎症和血管周围IgA沉积的疾病,这种疾病更常导致慢性肾脏病,占终末期肾病(ESRD)儿童的1%-2%。当前管理指南推荐的治疗原则包括一般药物治疗、支持措施和后遗症预防,其中治疗药物包括糖皮质激素、免疫抑制剂和血管紧张素系统抑制剂。然而,免疫抑制治疗的浓度范围狭窄且个体差异大,使用糖皮质激素似乎并不能改善IgAV儿童的持续性肾病和预后。因此,该疾病的个体化维持治疗和稳定的肾脏预后仍然是难题。基因信息有助于提前预测药物反应。已证明细胞色素氧化酶P450和药物转运体的大多数基因多态性会影响药物疗效和不良反应(ADR)。基于遗传学和药物基因组学的药物治疗有利于为儿童提供更安全、有效的治疗。本文基于IgAV的发病机制,总结了当前的治疗药物,探索潜在的治疗药物,并从药物基因组学层面重点探讨糖皮质激素和免疫抑制剂在IgAV肾炎儿童中的治疗意义。此外,分析了不同基因型IgAV儿童中糖皮质激素和免疫抑制剂的个体化应用,以便为IgAV肾炎儿童的个体化治疗提供更全面的参考。

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本文引用的文献

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The Efficacy of Glycosides Combined with LMWH in Treatment of HSPN in Children.糖苷联合低分子肝素治疗儿童过敏性紫癜性肾炎的疗效
Evid Based Complement Alternat Med. 2021 Oct 21;2021:7223613. doi: 10.1155/2021/7223613. eCollection 2021.

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