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Abstract：
Focal segmental glomerulosclerosis (FSGS) defines a distinct histologic pattern observed in kidney tissue that is linked to several distinct underlying causes, all converging on the common factor of podocyte injury. It presents a considerable challenge in terms of classification because of its varied underlying causes and the limited correlation between histopathology and clinical outcomes. Critically, precise nomenclature is key to describe and delineate the pathogenesis, subsequently guiding the selection of suitable and precision therapies. A proposed pathomechanism-based approach has been suggested for FSGS classification. This approach differentiates among primary, secondary, genetic, and undetermined causes, aiming to provide clarity. Genetic FSGS from monogenic mutations can emerge during childhood or adulthood, and it is advisable to conduct genetic testing in cases in which there is a family history of chronic kidney disease, nephrotic syndrome, or resistance to treatment. Genome-wide association studies have identified several genetic risk variants, such as those in apolipoprotein L1 (APOL1), that play a role in the development of FSGS. Currently, no specific treatments have been approved to treat genetic FSGS; however, interventions targeting underlying cofactor deficiencies have shown potential in some cases. Furthermore, encouraging results have emerged from a phase 2 trial investigating inaxaplin, a novel small molecule APOL1 channel inhibitor, in APOL1-associated FSGS.
摘要：
局灶节段肾小球硬化（FSGS）定义了在肾脏组织中观察到的独特组织学模式，该模式与几种不同的潜在原因有关。都集中在足细胞损伤的共同因素上。由于其不同的潜在原因以及组织病理学和临床结果之间的有限相关性，因此在分类方面提出了相当大的挑战。严重的,精确的命名是描述和描绘发病机理的关键，随后指导选择合适和精确的疗法。提出了一种基于病理机制的FSGS分类方法。这种方法区分了初级，次要,遗传,和不确定的原因，旨在提供清晰度。来自单基因突变的遗传FSGS可以在儿童或成年期出现，建议在有慢性肾病家族史的情况下进行基因检测，肾病综合征,或抵抗治疗。全基因组关联研究已经确定了几种遗传风险变异，例如载脂蛋白L1（APOL1），在FSGS的发展中发挥作用。目前,尚未批准治疗遗传性FSGS的特定治疗方法;然而，在某些情况下，针对潜在辅因子缺陷的干预措施显示出潜力。此外，令人鼓舞的结果已经出现从2期试验调查inaxaplin，一种新型小分子APOL1通道抑制剂，在APOL1相关的FSGS中。
