Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany.
Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University Tübingen, Tübingen, Germany.
Acta Physiol (Oxf). 2019 Apr;225(4):e13249. doi: 10.1111/apha.13249. Epub 2019 Jan 18.
Sodium retention and extracellular volume expansion are typical features of patients with nephrotic syndrome. In recent years, from in vitro data, endoluminal activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases has been proposed as an underlying mechanism. Recently, this concept was supported in vivo in nephrotic mice that were protected from proteolytic ENaC activation and sodium retention by the use of aprotinin for the pharmacological inhibition of urinary serine protease activity. These and other findings from studies in both rodents and humans highlight the impact of active proteases in the urine, or proteasuria, on ENaC-mediated sodium retention and edema formation in nephrotic syndrome. Targeting proteasuria could become a therapeutic approach to treat patients with nephrotic syndrome. However, pathophysiologically relevant proteases remain to be identified. In this review, we introduce the concept of proteasuria to explain tubular sodium avidity and conclude that proteasuria can be considered as a key mechanism of sodium retention in patients with nephrotic syndrome.
钠潴留和细胞外液体积扩张是肾病综合征患者的典型特征。近年来，从体外数据来看，异常滤过的丝氨酸蛋白酶对腔内上皮钠通道（ENaC）的激活被认为是一种潜在的机制。最近，这一概念在肾病小鼠体内得到了支持，这些小鼠通过使用抑肽酶抑制尿丝氨酸蛋白酶活性来防止蛋白水解 ENaC 激活和钠潴留。这些以及在啮齿动物和人类中进行的其他研究发现强调了尿液中或尿蛋白酶活性中活性蛋白酶对肾病综合征中 ENaC 介导的钠潴留和水肿形成的影响。针对尿蛋白酶可能成为治疗肾病综合征患者的一种治疗方法。然而，仍然需要确定与病理生理相关的蛋白酶。在这篇综述中，我们引入了尿蛋白酶的概念来解释管状钠吸收，并得出结论，尿蛋白酶可被视为肾病综合征患者钠潴留的关键机制。
