Nephrotic syndrome is associated with increased plasma K + concentration, intestinal K + losses, and attenuated urinary K + excretion: a study in rats and humans

Rikke Ydegaard, Per Svenningsen, Claus Bistrup, Rene Frydensbjerg Andersen, Jane Stubbe, Kristian Bergholt Buhl, Niels Marcussen, Gitte Rye Hinrichs, Hiba Iraqi, Reza Zamani, Henrik Dimke, Boye L Jensen

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Abstrakt

The present study tested the hypotheses that nephrotic syndrome (NS) leads to renal K + loss because of augmented epithelial Na + channel (ENaC) activity followed by downregulation of renal K + secretory pathways by suppressed aldosterone. The hypotheses were addressed by determining K + balance and kidney abundance of K + and Na + transporter proteins in puromycin aminonucleoside (PAN)-induced rat nephrosis. The effects of amiloride and angiotensin II type 1 receptor and mineralocorticoid receptor (MR) antagonists were tested. Glucocorticoid-dependent MR activation was tested by suppression of endogenous glucocorticoid with dexamethasone. Urine and plasma samples were obtained from pediatric patients with NS in acute and remission phases. PAN-induced nephrotic rats had ENaC-dependent Na + retention and displayed lower renal K + excretion but elevated intestinal K + secretion that resulted in less cumulated K + in NS. Aldosterone was suppressed at day 8. The NS-associated changes in intestinal, but not renal, K + handling responded to suppression of corticosterone, whereas angiotensin II type 1 receptor and MR blockers and amiloride had no effect on urine K + excretion during NS. In PAN-induced nephrosis, kidney protein abundance of the renal outer medullary K + channel and γ-ENaC were unchanged, whereas the Na +-Cl - cotransporter was suppressed and Na +-K +-ATPase increased. Pediatric patients with acute NS displayed suppressed urine Na +-to-K + ratios compared with remission and elevated plasma K + concentration, whereas fractional K + excretion did not differ. Acute NS is associated with less cumulated K + in a rat model, whereas patients with acute NS have elevated plasma K + and normal renal fractional K + excretion. In NS rats, K + balance is not coupled to ENaC activity but results from opposite changes in renal and fecal K + excretion with a contribution from corticosteroid MR-driven colonic secretion.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Renal Physiology
Vol/bind317
Udgave nummer6
Sider (fra-til)F1549-F1562
ISSN1931-857X
DOI
StatusUdgivet - 1. dec. 2019

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