Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD

Study Overview
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Brief Summary
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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
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The aim is to measure the acute effects of tolvaptan on: Renal hemodynamics (RPF, GFR, filtration fraction ((FF)) and renovascular resistance ((RVR)) Blood pressure (central blood pressure ((cBP)) and brachial blood pressure bBP) Several vasoactive hormones (plasma renin ((PRC)), plasma angiotensin II ((p-Ang-II)), plasma aldosterone ((p-Aldo)), plasma vasopressin ((p-AVP)) in patients with ADPKD.

Official Title
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Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD

Conditions
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Polycystic Kidney, Autosomal Dominant

Intervention / Treatment
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* Drug: Tolvaptan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tolvaptan<br>Drug: Tolvaptan 1 tablet before renography | Drug: Tolvaptan<br>* 1 tablet before renography<br>|
| Placebo Comparator: Placebo<br>Placebo 1 tablet before renography | Drug: Placebo<br>* 1 tablet before renography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal plasma flow (RPF) | Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min) | Two hours after trial medicine intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central and brachial blood pressures (BP) | Measured using Mobil-O-Graph® PWA (unit of measurement= mmHg) | Measured every 15 minutes during the examination day | 
| Glomerular filtration rate (GFR) | Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min) | Two hours after trial medicine intake | 
| Filtration fraction (FF) | Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= %) | Two hours after trial medicine intake | 
| Plasma concentration of vasopressin (p-AVP) | Blood samples (unit of measurement= pg/ml) | Measured before and 3 hours after trial medicine intake | 
| Plasma concentration of aldosterone (p-Aldo) | Blood samples (unit of measurement= pmol/ml) | Measured before and 3 hours after trial medicine intake | 
| Plasma concentration of angiotensin II (p-AngII) | Blood samples (unit of measurement= pg/ml) | Measured before and 3 hours after trial medicine intake | 
| Plasma concentration of renin (PRC) | Blood samples (unit of measurement= pg/ml) | Measured before and 3 hours after trial medicine intake | 
| Urine excretion of aquaporin 2 (u-AQP2) | Urine sample (unit of measurement= ng/ml) | Measured before and 3 hours after trial medicine intake | 
| Urine output (OU) | Urine sample (unit of measurement= ml/min) | Measured before and 3 hours after trial medicine intake | 
| Urine osmolality (U-osm) | Urine sample (unit of measurement= mosmol/kg) | measured before and 3 hours after trial medicine intake | 
| Fractional excretion of sodium (FENa) | Blood and urine sample (unit of measurement= %) | Measured before and 3 hours after trial medicine intake | 
| Albumin excretion rate | Blood and urine sample (unit of measurement= mg/min) | Measured before and 3 hours after trial medicine intake | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CYSTS, KIDNEYS