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

• Published in: American journal of physiology. Renal physiology Vol. 317; no. 6; pp. F1549 - F1562
• Main Authors: Ydegaard, Rikke, Svenningsen, Per, Bistrup, Claus, Andersen, Rene Frydensbjerg, Stubbe, Jane, Buhl, Kristian Bergholt, Marcussen, Niels, Hinrichs, Gitte Rye, Iraqi, Hiba, Zamani, Reza, Dimke, Henrik, Jensen, Boye L
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2019
• Subjects: Adolescent; Aldosterone; Aldosterone - metabolism; Amiloride; Amiloride - pharmacology; Angiotensin; Angiotensin II; Angiotensin II Type 2 Receptor Blockers - pharmacology; Animals; Child; Child, Preschool; Corticosteroids; Corticosterone; Dexamethasone; Diuretics; Down-Regulation; Epithelial Sodium Channels - metabolism; Excretion; Glucocorticoids; Humans; Hypotheses; Infant; Intestine; Kidney - drug effects; Kidney - metabolism; Kidney diseases; Kidneys; Male; Mineralocorticoid Receptor Antagonists - pharmacology; Na+/K+-exchanging ATPase; Nephrotic syndrome; Nephrotic Syndrome - blood; Nephrotic Syndrome - metabolism; Nephrotic Syndrome - urine; Pediatrics; Potassium - blood; Potassium - metabolism; Potassium - urine; Potassium channels; Potassium Channels - metabolism; Puromycin; Puromycin Aminonucleoside; Rats; Rats, Sprague-Dawley; Remission; Renal function; Secretion; Sodium; Sodium-Potassium-Exchanging ATPase - metabolism; Urine; channel; colon; potassium; edema; hypertension
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00179.2019

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 . 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.