ecallantide and Nephrotic-Syndrome

Recent work has demonstrated that activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases causes sodium retention in nephrotic syndrome. The aim of this study was to elucidate a potential role of plasma kallikrein (PKLK) as a candidate serine protease in this context.. We analysed PKLK in the urine of patients with chronic kidney disease (CKD, n = 171) and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in PKLK-deficient mice (klkb1. In patients with CKD, we found that PKLK is excreted in the urine up to a concentration of 2 μg mL. Plasma kallikrein is detected in the urine of proteinuric patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site. However, PKLK is not essential for volume retention in nephrotic mice.

Topics: Adult; Aged; Animals; Body Composition; Case-Control Studies; Disease Models, Animal; Doxorubicin; Epithelial Sodium Channels; Female; Humans; Kidney; Male; Membrane Potentials; Mice, Knockout; Middle Aged; Natriuresis; Nephrotic Syndrome; Organism Hydration Status; Plasma Kallikrein; Prospective Studies; Renal Elimination; Renal Insufficiency, Chronic; Water-Electrolyte Balance; Xenopus laevis