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

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 eGFR ≥60mL/min/1.73m 2 completed a 2-week low-salt run-in (≤3.5 g/day), then were randomized 1:1 to oral sodium chloride capsules (6 g/day) or placebo for 2 weeks, followed by a 2-week open-label amiloride (20 mg/day) add-on phase in both arms. The primary outcome was pulse wave velocity (PWV). Secondary outcomes included 24-hour blood pressure and biochemical parameters. Results Thirty-seven participants (mean age 39±11 years, eGFR 89±19 mL/min/1.73m 2 ) 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 blood pressure (133±13 mmHg to 138±15 mmHg, p=0.02). Amiloride did not reduce PWV in either group, but decreased systolic blood pressure only in the low-salt group (135±11 to 130±13 mmHg, 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 blood pressure in early ADPKD, and amiloride significantly lowered blood pressure only under low-salt conditions. These findings support dietary sodium restriction as a practical strategy for blood pressure and vascular protection in early ADPKD.