Autosomal Dominant Polycystic Kidney Disease
Conditions
Keywords
Tolvaptan, L-NMMA, ADPKD
Brief summary
Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive hormones. The purpose of the study is to measure the effects of tolvaptan on renal handling of water and sodium, systemic hemodynamics and vasoactive hormones at baseline and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA) in patients with autosomal dominant polycystic kidney disease.
Interventions
DRUGTolvaptan
60 mg Tolvaptan pr day for 1 day
DRUGPlacebo
1 tablet Unikalk pr day for 1 day
Sponsors
Aarhus University Hospital
Regional Hospital Holstebro
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Caucasian men and women 2. Age between 18-65 years 3. ADPKD, diagnosed by genetic testing of PKD1 (\>85%) or PKD2 mutations, or by ultrasonography: 1. patients with negative family history for ADKPD and more than 10 cysts in each kidney and no extrarenal or renal findings that suggest causes to cyst formation. 2. patients with positive family history for ADPKD: * 15-39 yr of age and at least 3 or more unilateral or bilateral. * 40-59 yr of age and 2 or more cysts in each kidney. * 60 yr of age and at least 4 cysts in each kidney. 4. Kidney function corresponding to CKD stages 1-3(eGFR\> 30 mL/min/1,73 m2), 5. BMI between 18.5 and 35.5 kg/m2.
Exclusion criteria
1. Clinical signs of diseases in the heart, lungs, endocrine organs, brain or neoplastic disease, 2. clinically significant abnormalities in blood or urine sample at the inclusion 3. previous cerebrovascular insults, 4. previous clinical evidence for aneurysm 5. Alcohol or drug abuse, 6. smoking, 7. pregnancy or breastfeeding, 8. clinically significant changes in the electrocardiogram, 9. medication except antihypertensive agents and oral contraceptives, 10. blood pressure\>170/105 mmHg despite treatment with metoprolol and/or amlodipine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CH2O (Measurement of H2O clearance) | 5-6 Hours | Measurement of H2O clearance at baseline, during and after L-NMMA infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ) | 5-6 Hours | — |
| Central and brachial blood pressure | 5-6 Hours | — |
| Augmentation Index | 5-6 Hours | — |
| Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin) | 5-6 Hours | — |
| Fractional sodium excretion | 5-6 Hours | Measurement of Sodium excretion at baseline, during and after L-NMMA infusion. |
Countries
Denmark
Outcome results
None listed