Time-course of sodium transport along the nephron in nephrotic syndrome: the role of potassium

Article Article scientifique Article Time-course of sodium transport along the nephron in nephrotic syndrome: the role of potassium eng 2020 author Bernabeu Dizin Eva 650786 author Olivier Valérie 0000-0001-9308-4853 889276 author Maire Charline 857169 author Komarynets Olga 831968 author Sassi Ali 0000-0002-3194-777X 882466 author Monnay Isabelle 510200 author Loffing Johannes author De Seigneux Matthey Sophie 105798 author Maillard Marc author Rutkowski Joseph M author Edwards Aurélie author Feraille Eric 27356 2408-2424 10.1096/fj.201901345R 31908015 0892-6638 The mechanism of sodium retention and its location in kidney tubules may vary with time in nephrotic syndrome (NS). We studied the mechanisms of sodium retention in transgenic POD-ATTAC mice, which display an inducible podocyte-specific apoptosis. At day 2 after the induction of NS, the increased abundance of NHE3 and phosphorylated NCC in nephrotic mice compared with controls suggest that early sodium retention occurs mainly in the proximal and distal tubules. At day 3, the abundance of NHE3 normalized, phosphorylated NCC levels decreased, and cleavage and apical localization of γ-ENaC increased in nephrotic mice. These findings indicate that sodium retention shifted from the proximal and distal tubules to the collecting system. Increased cleavage and apical localization of γ-ENaC persisted at day 5 in nephrotic mice when hypovolemia resolved and steady-state was reached. Sodium retention and γ-ENaC cleavage were independent of the increased plasma levels of aldosterone. Nephrotic mice displayed decreased glomerular filtration rate and urinary potassium excretion associated with hyperkaliemia at day 3. Feeding nephrotic mice with a low potassium diet prevented hyperkaliemia, γ-ENaC cleavage, and led to persistent increased phosphorylation of NCC. These results suggest that potassium homeostasis is a major determinant of the tubular site of sodium retention in nephrotic mice. Dewey 612 Swiss National Science Foundation Cell autonomous mechanisms of control of sodium transport in renal collecting duct 156736 CH Project funding Swiss National Science Foundation Mechanisms controlling sodium transport in the renal distal tubule 143929 CH Project funding 134 Département de physiologie cellulaire et métabolisme 21C false 20 Laboratoire de physiologie et pathophysiologie des cellules rénales 29 FASEB Journal 34 2 f58bd017-7e57-44d1-baa5-c313d0a2eb8a Article (Published version) Public fj.201901345R.pdf 1429133 application/pdf CC BY-NC-ND openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Time-course of sodium transport along the nephron in nephrotic syndrome: the role of potassium	FASEB Journal			2020	533	295

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