A Wu1, M Wolley1,2,A Douglas1, D Cowley1, M Stowasser1
1Endocrine Hypertension Research Centre, University of Queensland Faculty of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia, 2Royal Brisbane and Women’s Hospital Department of Nephrology, Brisbane, Australia
Aim: This study used urinary extracellular vesicles (uEVs) to investigate the acute oral KCl replacement on NCC abundance and phosphorylation in hypertensive patients with raised ARRs.
Background: NCC is the major transporter for Na+-Cl- reabsorption in the early distal convoluted tubule, and thought to be positively regulated by aldosterone and its analogues and negatively regulated by plasma potassium.
Methods: Plasma potassium concentration was measured at 7AM on the morning after admission. If potassium was less than 4.0 mmol/l, participants were given sufficient slow-release KCl (Span K) up to Q6h to achieve as close to 4.0 mmol/l as possible by the next morning at 7AM. uEVs were harvested by progressive ultracentrifugation and analysed by immunoblotting.
Results: Among 25 (F16/M9) participants who were given a median of 6.0 [2.4, 16.8] g KCl within 24-hour, plasma potassium increased (p<0.001) from a median of 3.4 [2.8, 3.9] to [3.1, 4.7] mmol/L, NCC (p<0.01), pT53/58-NCC (p<0.01) and pT58-NCC (p<0.05) decreased by up to a median of 30%. Whilst in the 13 (F8/M5) who were not given KCl, plasma potassium, NCC expression and phosphorylation remained unchanged. Increases in plasma aldosterone and renin were observed in both groups. Abundance of NCC (R2=0.14, p<0.05), pT53/58-NCC (R2=0.26, p<0.0001) and pT58-NCC (R2=0.16, p<0.001) were inversely correlated plasma potassium. Comparing to that in subjects whose plasma potassium were ≥4.0mmol/L., NCC, pT53/58-NCC and pT58-NCC were relatively abundant in subjects presenting hypokalaemia
Conclusions: 24-Hour oral KCl loading increased plasma potassium in hypertensive patients with raised ARRs, and is associated with decreases in NCC abundance and phosphorylation in uEVs, and plasma potassium may override the effects of aldosterone on NCC.
Aihua is a Third-year PhD student interested in the regulation of sodium chloride cotransporter (NCC) in health and disease of salt homeostasis.