Reduced NaCl cotransporter abundance and phosphorylation in urinary extracellular vesicles in response to KCl supplements in healthy adults maintained on a high-Na+ low-K+ diet: A

No Thumbnail Available
File version
Author(s)
Wu, Aihua
Wolley, Martin
Mayr, Hannah
Cowley, Diane
Li, Bo
Welling, Paul
Campbell, Katrina
Fenton, Robert
Stowasser, Michael
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2022
Size
File type(s)
Location

Athens, Greece

License
Abstract

Objective: A renal-K switch mechanism has been established in rodent models and demonstrates that a low K+ intake acts as a trigger that links K+ and Na+-dependent blood pressure. This mechanism involves activation (phosphorylation) of the NaCl-cotransporter NCC in the distal convoluted tubule in response to low-K+ intake and suppression (dephosphorylation) after a high-K+ intake. As a first step to establishing a similar mechanism in humans, this study aimed to examine if the abundance of NCC and pNCC in urinary extracellular vesicles (uEVs) of healthy adults on a high-Na+ diet changes in response to alterations in K+ intake.

Design and method: The study design was a double-blind, randomised and placebo-controlled trial. Healthy adults maintained on a high-Na+ (∼200mmol/day), low-K+ (∼60mmol/day) diet underwent a run-in period of 1-week followed by a cross-over study, with 5 days supplementary KCl (active phase, Span K, 24mmol thrice daily) or 5 days placebo administered in random order and separated by 2 days washout. NCC and pNCC were measured in uEVs after each phase. Participants who met dietary compliance (no less than 80%) and increased urinary K+ in the active phase were included in analyses.

Results: Among the 18 (out of 28) participants who met inclusion criteria, supplementary KCl administration (versus placebo) in the active phase was associated with higher levels of plasma K+ (p < 0.001) and 24-Hour urine levels of K+ (p < 0.001), Cl- (p < 0.001) and aldosterone (p < 0.001), and lower levels of 24-Hour urinary Na+/K+ (p < 0.001), NCC (p < 0.01) and pNCC (p < 0.05); whilst the ratio of pNCC/NCC remained unchanged. Correlation analyses revealed an inverse correlation of plasma K+ with NCC (R2 = 0.11, p = 0.05) and δurinary K+ with δpNCC (R2 = 0.23, p = 0.04). Ambulatory systolic blood pressure positively correlated with timed urinary Na+/K+ (R2 = 0.08, p = 0.04) during interventions.δ

Conclusions: KCl supplementation in healthy adult subjects maintained on a high-Na+ low-K+ diet was associated with a fall in NCC and pNCC, consistent with the renal-K switch mechanism, and offers a useful target for dietary intervention.

Journal Title

Journal of Hypertension

Conference Title

ESH 2022 Abstract Book

Book Title
Edition
Volume

40

Issue

Suppl 1

Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject

Clinical sciences

Medical physiology

Nephrology and urology

Cardiovascular System & Cardiology

Life Sciences & Biomedicine

Peripheral Vascular Disease

Science & Technology

Persistent link to this record
Citation

Wu, A; Wolley, M; Mayr, H; Cowley, D; Li, B; Welling, P; Campbell, K; Fenton, R; Stowasser, M, Reduced NaCl cotransporter abundance and phosphorylation in urinary extracellular vesicles in response to KCl supplements in healthy adults maintained on a high-Na+ low-K+ diet: A, Journal of Hypertension, 2022, 40 (Suppl 1), pp. E6-E6