Clement Lionel C, Macé Camille, Del Nogal Avila Maria, Marshall Caroline B, Chugh Sumant S
Glomerular Disease Therapeutics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Glomerular Disease Therapeutics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama.
Transl Res. 2015 Apr;165(4):499-504. doi: 10.1016/j.trsl.2014.06.004. Epub 2014 Jun 18.
The development of new and specific treatment options for kidney disease in general and glomerular diseases in specific has lagged behind other fields like heart disease and cancer. As a result, nephrologists have had to test and adapt therapeutics developed for other indications to treat glomerular diseases. One of the major factors contributing to this inertia has been the poor understanding of disease mechanisms. One way to elucidate these disease mechanisms is to study the association between the cardinal manifestations of glomerular diseases. Because many of these patients develop nephrotic syndrome, understanding the relationship of proteinuria, the primary driver in this syndrome, with hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, edema, and lipiduria could provide valuable insight. The recent unraveling of the relationship between proteinuria and hypertriglyceridemia mediated by free fatty acids, albumin, and the secreted glycoprotein angiopoietin-like 4 (Angptl4) offers a unique opportunity to develop novel therapeutics for glomerular diseases. In this review, the therapeutic potential of mutant forms of Angptl4 in reducing proteinuria and, as a consequence, alleviating the other manifestations of nephrotic syndrome is discussed.
总体而言，针对肾脏疾病尤其是肾小球疾病的新型特异性治疗方案的开发落后于心脏病和癌症等其他领域。因此，肾病学家不得不测试并调整针对其他适应症开发的疗法来治疗肾小球疾病。造成这种惰性的主要因素之一是对疾病机制的了解不足。阐明这些疾病机制的一种方法是研究肾小球疾病主要表现之间的关联。由于这些患者中有许多会发展为肾病综合征，了解蛋白尿（该综合征的主要驱动因素）与低白蛋白血症、高胆固醇血症、高甘油三酯血症、水肿和脂尿之间的关系可能会提供有价值的见解。最近对由游离脂肪酸、白蛋白和分泌型糖蛋白血管生成素样4（Angptl4）介导的蛋白尿与高甘油三酯血症之间关系的揭示，为开发针对肾小球疾病的新型疗法提供了独特的机会。在这篇综述中，讨论了Angptl4突变形式在减少蛋白尿以及由此减轻肾病综合征其他表现方面的治疗潜力。
