Treatment of Vascular Stiffness in ADPKD

Objective of the study:

The investigators aim to investigate if arterial stiffness is exacerbated due to a high-salt diet in patients with ADPKD. The investigators also aim to explore whether treatment with amiloride prevents the arterial stiffness caused by a high-salt diet.

Study design:

Randomized, double blinded and placebo-controlled clinical trial with open-label treatment with amiloride

Study population:

Adults with ADPKD with an estimated glomerular filtration rate (CKD-EPI) of ≥ 60 ml/min/1.73m2

Intervention:

All participants will be subjected to a low-salt diet (3,5 grams/day) throughout the study for a total of 6 weeks. After a run-in period of 2 weeks, participants will be randomized into two treatment groups:

Group 1: Sodium chloride capsules (6 grams/day) for 2 weeks, combined with amiloride (20 mg/day) in last 2 weeks Group 2: Placebo capsules for 2 weeks, combined with amiloride (20 mg/day) in last 2 weeks.

Primary study parameters/outcome of the study:

The three primary outcomes of this study are a difference in central arterial stiffness (pulse wave velocity, PWV) between:

• The high-salt group versus low-salt group;
• The high-salt group: before versus after amiloride treatment;
• The low-salt group: before versus after amiloride treatment.

The burden of participation includes:

• A dietary salt restriction of 3.5 grams/day for a total period of 6 weeks
• Salt supplementation or placebo for a total period of 4 weeks
• Drug intervention with amiloride during the last 2 weeks
• Hospital visits

Inclusion criteria

• Adults with typical ADPKD diagnosed based on Ravine criteria and/or a documented Pkd 1 or 2 mutation
• Chronic kidney disease epidemiology collaboration equation estimated glomerular filtration rate ≥60 ml/min/1.73m2
• Ability to provide informed consent

Exclusion criteria

• Uncontrolled hypertension, defined as an office blood pressure of ≥160/ ≥90 mmHg with or without antihypertensive treatment
• Concomitant use of ≥ 3 antihypertensive medications
• When antihypertensive treatment is prescribed for any other treatment indication than hypertension (e.g. cardia arrhythmia)
• Serum potassium levels >5.5 mmol/L (measured within last 6 months)
• History of liver disease (excluding liver cysts due to ADPKD)
• History of heart failure (cardiac ejection fraction < 35%) or cardiac arrhythmia
• History of diabetes mellitus
• Active infection or antibiotic therapy
• Immunosuppressive therapy within the last year
• Concomitant use of drugs that could influence blood pressure and/or disease progression (Tolvaptan/non-steroidal anti-inflammatory drugs (NSAIDs)/chemotherapy), excluding < 3 antihypertensive drugs
• Actual pregnancy or unwillingness to adhere to reproductive precautions during the duration of the study