Randomized Controlled Trial of Salt and Amiloride on Vascular Stiffness in ADPKD

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.

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.

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.

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.