Randomized Controlled Trial of Salt and Amiloride on Vascular Stiffness in ADPKD
6 affiliations
- 1Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- 2Division of Dietetics, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- 3Department of Internal Medicine, Franciscus Hospital, Rotterdam, The Netherlands
- 4Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands
- 5Department of Internal Medicine, Haga Hospital, The Hague, The Netherlands
- 6Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Abstract
Introduction: Patients with autosomal dominant polycystic kidney disease (ADPKD) often develop early vascular stiffening and hypertension. Dietary sodium may worsen vascular stiffness via epithelial sodium channel (ENaC) activation, and ENaC inhibition might mitigate this, but this remains untested in ADPKD. We hypothesized that dietary sodium loading increases vascular stiffness in ADPKD and that the ENaC inhibitor amiloride attenuates this effect.
Methods: In this double-blind, randomized, placebo-controlled trial, adults with ADPKD and estimated glomerular filtration rate (eGFR) ≥60 ml/min per 1.73 m2 completed a 2-week low-salt run-in (≤ 3.5 g/d), then were randomized 1:1 to oral sodium chloride capsules (6 g/d) or placebo for 2 weeks, followed by a 2-week open-label amiloride (20 mg/d) add-on phase in both arms. The primary outcome was pulse wave velocity (PWV). Secondary outcomes included 24-hour blood pressure (BP) and biochemical parameters.
Results: Thirty-seven participants (mean age 39 ± 11 years, eGFR 89 ± 19 ml/min per 1.73 m2) were randomized to salt (n = 19) or placebo (n = 18). Salt supplementation increased PWV (6.5 ± 0.9 m/s to 6.8 ± 1.1 m/s, P = 0.02) and 24-hour systolic BP (133 ± 13 mm Hg to 138 ± 15 mm Hg, P = 0.02). Amiloride did not reduce PWV in either group, but decreased systolic BP only in the low-salt group (135 ± 11 to 130 ± 13 mm Hg, P = 0.03). Plasma potassium increased modestly in both groups following amiloride, without hyperkalemia.
Conclusion: In this small, short-term trial, dietary sodium significantly increased vascular stiffness and BP in early ADPKD, and amiloride significantly lowered BP only under low-salt conditions. These findings support dietary sodium restriction as a practical strategy for BP and vascular protection in early ADPKD.
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BibTeX
@article{noruzi2026randomized,
title = {{Randomized Controlled Trial of Salt and Amiloride on Vascular Stiffness in ADPKD}},
author = {Anahita Noruzi and Laixi Xue and Wesley J. Visser and Robert Zietse and Joep van der Leeuw and Jeroen van der Net and Darius Soonawala and Sanne C.M. Boeters and A.H. Jan Danser and Ewout J. Hoorn and Mahdi Salih},
journal = {Kidney International Reports},
year = {2026},
month = sep,
doi = {10.1016/j.ekir.2026.107110},
url = {https://doi.org/10.1016/j.ekir.2026.107110},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Randomized Controlled Trial of Salt and Amiloride on Vascular Stiffness in ADPKD
AU - Anahita Noruzi
AU - Laixi Xue
AU - Wesley J. Visser
AU - Robert Zietse
AU - Joep van der Leeuw
AU - Jeroen van der Net
AU - Darius Soonawala
AU - Sanne C.M. Boeters
AU - A.H. Jan Danser
AU - Ewout J. Hoorn
AU - Mahdi Salih
PY - 2026
DA - 2026/09/23
JO - Kidney International Reports
DO - 10.1016/j.ekir.2026.107110
UR - https://doi.org/10.1016/j.ekir.2026.107110
AB - Introduction: Patients with autosomal dominant polycystic kidney disease (ADPKD) often develop early vascular stiffening and hypertension. Dietary sodium may worsen vascular stiffness via epithelial sodium channel (ENaC) activation, and ENaC inhibition might mitigate this, but this remains untested in ADPKD. We hypothesized that dietary sodium loading increases vascular stiffness in ADPKD and that the ENaC inhibitor amiloride attenuates this effect. Methods: In this double-blind, randomized, placebo-controlled trial, adults with ADPKD and estimated glomerular filtration rate (eGFR) ≥60 ml/min per 1.73 m2 completed a 2-week low-salt run-in (≤ 3.5 g/d), then were randomized 1:1 to oral sodium chloride capsules (6 g/d) or placebo for 2 weeks, followed by a 2-week open-label amiloride (20 mg/d) add-on phase in both arms. The primary outcome was pulse wave velocity (PWV). Secondary outcomes included 24-hour blood pressure (BP) and biochemical parameters. Results: Thirty-seven participants (mean age 39 ± 11 years, eGFR 89 ± 19 ml/min per 1.73 m2) were randomized to salt (n = 19) or placebo (n = 18). Salt supplementation increased PWV (6.5 ± 0.9 m/s to 6.8 ± 1.1 m/s, P = 0.02) and 24-hour systolic BP (133 ± 13 mm Hg to 138 ± 15 mm Hg, P = 0.02). Amiloride did not reduce PWV in either group, but decreased systolic BP only in the low-salt group (135 ± 11 to 130 ± 13 mm Hg, P = 0.03). Plasma potassium increased modestly in both groups following amiloride, without hyperkalemia. Conclusion: In this small, short-term trial, dietary sodium significantly increased vascular stiffness and BP in early ADPKD, and amiloride significantly lowered BP only under low-salt conditions. These findings support dietary sodium restriction as a practical strategy for BP and vascular protection in early ADPKD.
SN - 2468-0249
ER -