Department of Pediatrics, Division of Nephrology, NYU Langone Health , New York, NY, USA.
Expert Opin Emerg Drugs. 2020 Sep;25(3):367-375. doi: 10.1080/14728214.2020.1803276. Epub 2020 Aug 12.
Glomerulosclerosis represents the final stage of glomerular injury during the course of kidney disease and can result from a primary disturbance in disorders like focal segmental glomerulosclerosis or a secondary response to tubulointerstitial disease. Overall, primary focal glomerulosclerosis (FSGS), the focus of this review, accounts for 10-20% of patients of all ages who progress to end stage kidney disease. There are no FDA approved therapeutic options that effectively prevent or delay the onset of kidney failure.
Current immunosuppressive therapy and conservative management including inhibitors of the renin-angiotensin-aldosterone axis and sodium-glucose cotransporter are reviewed. FSGS is now recognized to represent a heterogeneous entity with multiple underlying disease mechanisms. Therefore, novel approaches targeting the podocyte cytoskeleton, immunological, inflammatory, hemodynamic and metabolic pathways are highlighted.
A number of factors are driving the development of drugs to treat focal segmental glomerulosclerosis in particular and glomerulosclerosis in general including growing awareness of the burden of chronic kidney disease, improved scientific understanding of the mechanism of injury, and the development of noninvasive profiles to identify subgroups of patients with discrete mechanisms of glomerular injury.
肾小球硬化症是肾脏疾病过程中肾小球损伤的终末阶段，可由局灶节段性肾小球硬化症等原发性疾病紊乱引起，也可继发于肾小管间质疾病。总的来说，本综述的重点是原发性局灶节段性肾小球硬化症（FSGS），在所有年龄段进展为终末期肾病的患者中占 10-20%。目前尚无获得 FDA 批准的治疗方法可有效预防或延缓肾衰竭的发生。
本文综述了当前的免疫抑制治疗和保守治疗，包括肾素-血管紧张素-醛固酮轴抑制剂和钠-葡萄糖共转运蛋白抑制剂。FSGS 现在被认为是一种具有多种潜在疾病机制的异质性实体。因此，针对足细胞细胞骨架、免疫、炎症、血液动力学和代谢途径的新型方法被强调。
许多因素正在推动治疗局灶节段性肾小球硬化症，特别是肾小球硬化症药物的开发，包括对慢性肾脏病负担的认识不断提高、对损伤机制的科学理解不断提高，以及开发非侵入性谱来识别具有不同肾小球损伤机制的患者亚组。
