Nephrotic syndrome is associated with increased plasma K+ concentration, intestinal K+ losses and attenuated urinary K+ excretion - studies 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
2019 AJP - Renal Physiology  
The present study tested the hypotheses that nephrotic syndrome (NS) leads to renal K+ loss due to augmented ENaC activity followed by down-regulation 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. Effect of amiloride and angiotensin II-AT1 and mineralocorticoid receptor (MR) antagonists were tested.
more » ... dependent MR activation was tested by suppression of endogenous glucocorticoid with dexamethasone. Urine and plasma samples were obtained from pediatric NS-patients in acute and remission-phase. PAN-nephrotic rats had ENaC dependent Na+ retention; 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, while ATI and MR blockers and amiloride had no effect on urine K+ excretion during NS. In PAN-nephrosis, kidney protein abundances of ROMK and γENaC were unchanged while NCC was suppressed and Na+-K+-ATPase increased. Acute pediatric NS patients displayed suppressed urine Na+/K+ ratio compared to remission and elevated plasma K+ concentration, while fractional K+ excretion did not differ. Acute NS is associated with less cumulated K+ in a rat model while acute NS-patients have elevated p-potassium 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 contribution from corticosteroid-MR driven colonic secretion.
doi:10.1152/ajprenal.00179.2019 pmid:31566427 fatcat:fcv22kysxrcdrkvzaqlu7kdbjm