Malaga-Dieguez Laura, Bouhassira Diana, Gipson Debbie, Trachtman Howard
Division of Nephrology, Department of Pediatrics, CS Mott Children's Hospital; and NYU Langone Medical Center, New York, NY.
Division of Nephrology, Department of Pediatrics, CS Mott Children's Hospital; and NYU Langone Medical Center, New York, NY.
Adv Chronic Kidney Dis. 2015 Mar;22(2):e1-6. doi: 10.1053/j.ackd.2014.10.001.
Focal segmental glomerulosclerosis (FSGS) is a rare but important cause of end-stage kidney disease in children and adults. Current therapy, consisting of corticosteroids and calcineurin inhibitors, fails to achieve a sustained remission in most patients. Therefore, there is a pressing need to develop new treatments for this glomerulopathy. Traditional approaches have focused on agents that modulate the immune system. In this review, we summarize preclinical and clinical data with newer agents that may ameliorate FSGS. We focus on drugs that inhibit immune injury or inflammation, such as abatacept, rituximab, adalimumab, and stem cells. The potential of agents that block the glomerular action of circulating permeability factors such as soluble urokinase receptor is reviewed. Finally, because fibrosis represents the final common pathway of glomerular damage in FSGS, the experience with a wide range of antifibrotic agents is presented. Despite extensive research on the podocyte dysfunction in the pathogenesis of FSGS, there are few agents that directly target podocyte structure or viability. We conclude that FSGS is a heterogeneous disorder and that intensified translational research is vital to improve our understanding of distinct subtypes that have a defined prognosis and predictable response to targeted therapeutic interventions.
局灶节段性肾小球硬化（FSGS）是儿童和成人终末期肾病的一种罕见但重要的病因。目前由皮质类固醇和钙调神经磷酸酶抑制剂组成的治疗方法，在大多数患者中未能实现持续缓解。因此，迫切需要为这种肾小球病开发新的治疗方法。传统方法主要集中在调节免疫系统的药物上。在本综述中，我们总结了使用可能改善FSGS的新型药物的临床前和临床数据。我们重点关注抑制免疫损伤或炎症的药物，如阿巴西普、利妥昔单抗、阿达木单抗和干细胞。还综述了阻断循环通透性因子（如可溶性尿激酶受体）肾小球作用的药物的潜力。最后，由于纤维化是FSGS中肾小球损伤的最终共同途径，本文介绍了广泛的抗纤维化药物的使用经验。尽管对FSGS发病机制中的足细胞功能障碍进行了广泛研究，但直接针对足细胞结构或活力的药物很少。我们得出结论，FSGS是一种异质性疾病，加强转化研究对于提高我们对具有明确预后和对靶向治疗干预有可预测反应的不同亚型的理解至关重要。
