In Primary Aldosteronism Acute Potassium Chloride Supplementation Suppresses Abundance and Phosphorylation of the Sodium-Chloride Cotransporter


Elevated abundance of sodium-chloride cotransporter (NCC) and phosphorylated NCC (pNCC) are potential markers of primary aldosteronism (PA), but these effects may be driven by hypokalaemia. We measured plasma potassium in PA patients. If potassium was <4.0 mmol/L, patients were given sufficient oral potassium chloride (KCl) over 24 hours to achieve as close to 4.0 mmol/L as possible. Clinical chemistries were assessed and urinary extracellular vesicles (uEVs) were examined to investigate effects on NCC. Among 21 PA patients who received a median total dose of 6.0 [2.4, 16.8] g KCl, increases were observed in plasma potassium (from 3.4 to 4.0 mmol/L, P<0.001), aldosterone (305 to 558 pmol/L, P=0.01) and renin (1.2 to 2.5 mU/L, P<0.001), while decreases were detected in uEV levels of NCC (median fold change(post/basal) [FC]= 0.71 [0.09, 1.99], P=0.02), pT60-NCC (FC=0.84 [0.06, 1.66], P=0.05) and pT55/60-NCC (FC=0.67 [0.08, 2.42], P=0.02). By contrast, in 10 PA patients who did not receive KCl, there were no apparent changes in plasma potassium, NCC abundance and phosphorylation status, but increases were observed in plasma aldosterone (from 178 to 418 pmol/L, P=0.006) and renin (2.0 to 3.0 mU/L, P=0.009). Plasma potassium correlated inversely with uEV levels of NCC (R2=0.11, P=0.01), pT60-NCC (R2=0.11, P=0.01) and pT55/60-NCC (R2=0.11, P=0.01). Acute oral KCl loading replenished plasmapotassium in PA patients and suppressed NCC abundance and phosphorylation despite a significant rise in plasma aldosterone. This supports the view that potassium supplementation in humans with PA overrides the aldosterone stimulatory effect on NCC. The increased plasma aldosterone in PA patients without KCl supplementation may be due to aldosterone response to posture challenge.

Authors: Aihua Wu, Martin J. Wolley, Alexandra Matthews, Diane Cowley, Paul A. Welling, Robert A. Fenton, Michael Stowasser
Keywords: potassium chloride, supplementation, sodium chloride cotransporter
DOI Number: 10.34067/KID.0003632022      Publication Year: 2022

To search for other research papers by topic, keyword, author, or year, please go to our Publications page.