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Proteasuria—The impact of active urinary proteases on sodium retention in nephrotic syndrome
Author(s) -
Artunc Ferruh,
Wörn Matthias,
Schork Anja,
Bohnert Bernhard N.
Publication year - 2019
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13249
Subject(s) - proteases , nephrotic syndrome , epithelial sodium channel , kallikrein , serine , sodium , chemistry , serine protease , urinary retention , aprotinin , medicine , protease , endocrinology , pharmacology , biochemistry , enzyme , urology , organic chemistry
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.