Podocytopathies.
Podocytopathies.
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DOI：
10.1038/s41572-020-0196-7
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发表时间：
2020-08-13
期刊：
影响因子：
--
通讯作者：
Romagnani P
中科院分区：
文献类型：
--
作者：
Kopp JB;Anders HJ;Susztak K;Podestà MA;Remuzzi G;Hildebrandt F;Romagnani P
足细胞病变是指直接或间接足细胞损伤导致蛋白尿或肾病综合征的肾脏疾病。在儿童和年轻人中，足细胞表达基因、综合症非足细胞特异性基因和带有其他潜在遗传异常的表型变异会导致与类固醇抵抗型肾病综合征或严重蛋白尿相关的足细胞病变。各种基因变异可能会导致疾病的发展。在非孟德尔遗传的基因中，APOL1的变异具有最大的效应大小。除了遗传变异外，环境因素，如免疫相关、感染相关、毒性和血液动力学因素以及肥胖也是足细胞损伤的重要原因，并经常结合在一起导致儿童和成人不同程度的蛋白尿。肾活检的典型表现为微小病变和局灶节段性肾小球硬化病变。对表现为局灶节段性肾小球硬化性损害的原发足细胞病变的标准治疗包括糖皮质激素和其他免疫抑制药物；对蛋白尿无反应的患者肾脏预后较差。肾素-血管紧张素系统拮抗剂有助于控制蛋白尿，减缓纤维化的进展。对症治疗可能包括使用利尿剂、他汀类药物、预防感染和抗凝。这本入门读物讨论了从基于肾活检结果的患者分层到基于临床、形态和遗传数据以及病理生理理解的个性化管理的范式的转变。
Podocytopathies are kidney diseases in which direct or indirect podocyte injury drives proteinuria or nephrotic syndrome. In children and young adults, genetic variants in >50 podocyte-expressed genes, syndromal non-podocyte-specific genes and phenocopies with other underlying genetic abnormalities cause podocytopathies associated with steroid-resistant nephrotic syndrome or severe proteinuria. A variety of genetic variants likely contribute to disease development. Among genes with non-Mendelian inheritance, variants in APOL1 have the largest effect size. In addition to genetic variants, environmental triggers such as immune-related, infection-related, toxic and haemodynamic factors and obesity are also important causes of podocyte injury and frequently combine to cause various degrees of proteinuria in children and adults. Typical manifestations on kidney biopsy are minimal change lesions and focal segmental glomerulosclerosis lesions. Standard treatment for primary podocytopathies manifesting with focal segmental glomerulosclerosis lesions includes glucocorticoids and other immunosuppressive drugs; individuals not responding with a resolution of proteinuria have a poor renal prognosis. Renin–angiotensin system antagonists help to control proteinuria and slow the progression of fibrosis. Symptomatic management may include the use of diuretics, statins, infection prophylaxis and anticoagulation. This Primer discusses a shift in paradigm from patient stratification based on kidney biopsy findings towards personalized management based on clinical, morphological and genetic data as well as pathophysiological understanding.
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