Polycystic Kidney, Autosomal Dominant
Conditions
Keywords
CYSTS, KIDNEYS
Brief summary
Polycystic kidney disease (ADPKD) is a common genetic disorder, characterized by the formation of cysts in the kidneys, causing gradual renal function-loss. Previous studies have shown that, reduced glomerular filtration rate (GFR) and renal plasma flow (RPF) play a role in the progression of renal disease in ADPKD. Tolvaptan is a vasopressin 2 antagonist, which seems to reduce the growth of total kidney volume (TKV) and the decline in e-GFR in ADPKD. The mechanism is not fully understood and could, at least partly, be caused by stimulation of the renal blood flow. The purpose of this trial is to investigate if tolvaptan´s improve renal blood flow and glomerular filtration in ADPKD, in a randomized, cross-over, double-blind, placebo-controlled study.
Detailed description
The aim is to measure the acute effects of tolvaptan on: 1. Renal hemodynamics (RPF, GFR, filtration fraction ((FF)) and renovascular resistance ((RVR)) 2. Blood pressure (central blood pressure ((cBP)) and brachial blood pressure bBP) 3. Several vasoactive hormones (plasma renin ((PRC)), plasma angiotensin II ((p-Ang-II)), plasma aldosterone ((p-Aldo)), plasma vasopressin ((p-AVP)) in patients with ADPKD.
Interventions
DRUGTolvaptan
1 tablet before renography
DRUGPlacebo
1 tablet before renography
Sponsors
Regional Hospital Holstebro
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Diagnosis with ADPKD * Informed consent * Contraception for fertile women
Exclusion criteria
* Renal transplantation * Operation in the kidney * Diabetes mellitus * Neoplastic conditions * Pregnancy, nursing * Unwillingness to participate * eGFR \> 30 * Intolerance towards tolvaptan * Alcohol or medical abuse, * BP \>\>170/110 blood pressure despite regulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal plasma flow (RPF) | Two hours after trial medicine intake | Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glomerular filtration rate (GFR) | Two hours after trial medicine intake | Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min) |
| Filtration fraction (FF) | Two hours after trial medicine intake | Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= %) |
| Plasma concentration of vasopressin (p-AVP) | Measured before and 3 hours after trial medicine intake | Blood samples (unit of measurement= pg/ml) |
| Plasma concentration of aldosterone (p-Aldo) | Measured before and 3 hours after trial medicine intake | Blood samples (unit of measurement= pmol/ml) |
| Plasma concentration of angiotensin II (p-AngII) | Measured before and 3 hours after trial medicine intake | Blood samples (unit of measurement= pg/ml) |
| Central and brachial blood pressures (BP) | Measured every 15 minutes during the examination day | Measured using Mobil-O-Graph® PWA (unit of measurement= mmHg) |
| Urine excretion of aquaporin 2 (u-AQP2) | Measured before and 3 hours after trial medicine intake | Urine sample (unit of measurement= ng/ml) |
| Urine output (OU) | Measured before and 3 hours after trial medicine intake | Urine sample (unit of measurement= ml/min) |
| Urine osmolality (U-osm) | measured before and 3 hours after trial medicine intake | Urine sample (unit of measurement= mosmol/kg) |
| Fractional excretion of sodium (FENa) | Measured before and 3 hours after trial medicine intake | Blood and urine sample (unit of measurement= %) |
| Albumin excretion rate | Measured before and 3 hours after trial medicine intake | Blood and urine sample (unit of measurement= mg/min) |
| Plasma concentration of renin (PRC) | Measured before and 3 hours after trial medicine intake | Blood samples (unit of measurement= pg/ml) |
Countries
Denmark
Outcome results
None listed