Guo Hong-Li, Li Ling, Xu Ze-Yue, Jing Xia, Xia Ying, Qiu Jin-Chun, Ji Xing, Chen Feng, Xu Jing, Zhao Fei
Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing 210008, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Curr Pharm Des. 2021;27(2):319-329. doi: 10.2174/1381612826666201102104412.
Steroid-resistant nephrotic syndrome (SRNS) constitutes the second most frequent cause of chronic kidney disease in childhood. The etiology of SRNS remains largely unknown and no standardized treatment exists. Recent advances in genomics have helped to build understanding of the molecular mechanisms and pathogenesis of the disease. The genetic polymorphisms in genes encoding proteins which are involved in the pharmacokinetics and pharmacodynamics of glucocorticoids (GCs) partially account for the different responses between patients with nephrotic syndrome. More importantly, single-gene causation in podocytes-associated proteins was found in approximately 30% of SRNS patients. Some potential biomarkers have been tested for their abilities to discriminate against pediatric patients who are sensitive to GCs treatment and patients who are resistant to the same therapy. This article reviews the recent findings on genetic mechanisms, predictive biomarkers and current therapies for SRNS with the goal to improve the management of children with this syndrome.
类固醇抵抗性肾病综合征（SRNS）是儿童慢性肾脏病的第二大常见病因。SRNS的病因在很大程度上仍不清楚，且尚无标准化治疗方法。基因组学的最新进展有助于增进对该疾病分子机制和发病机制的理解。编码参与糖皮质激素（GCs）药代动力学和药效动力学的蛋白质的基因中的遗传多态性，部分解释了肾病综合征患者之间的不同反应。更重要的是，在约30%的SRNS患者中发现了足细胞相关蛋白的单基因病因。一些潜在的生物标志物已被测试其区分对GCs治疗敏感的儿科患者和对相同治疗耐药的患者的能力。本文综述了SRNS的遗传机制、预测性生物标志物和当前治疗的最新研究结果，旨在改善对患有该综合征儿童的管理。
