Nephropathy
Conditions
Keywords
Nephrology, sodium-channels, water-channels, BCM, central blood pressure
Brief summary
Urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2) reflects the activity of the sodium- and water channels in the human kidney. Changes in the sodium-and water channel activity can be induced by blocking the sodium channels with diuretics in healthy subjects
Detailed description
1. Urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2) reflects the kidneys transport of sodium and water in the nephron. 2. Changes in the sodium-and water channel activity is induced by blocking the NCC channels with thiazide and ENaC channels with amiloride and by intervention with hypertonic NaCl The changes in sodium-and water channels are followed by changes in extracellular and intracellular fluids, central bloodpressure and the plasma concentration of vasoactive hormones. The purpose of this study is to investigate the changes in urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2), extra- and intracellular fluid compartments, central bloodpressure and the plasma concentration of Vasoactive hormones in healthy subjects under a) treatment with Amiloride and Thiazide at baseline and b) after and acute infusion with hypertonic saline. Subjects will be examined on three examination days. Four days prior to the examination days the subjects will consume a standard diet based on amount of sodium and calories and randomized to treatment with either thiazide, amiloride or placebo twice daily for 5 days. On the examination days the subjects receive an infusion with hypertonic saline. Renal function is measured by renal clearance of 51Cr-EDTA. Urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2) will be measured to evaluate the activity of water- and sodium channels in the nephron, changes in fluid compartments are measured by body composition monitor. Central blood pressure is measured by sphygmocor.
Interventions
OTHERhypertonic saline
hypertonic saline 3.0% 7 ml/kg
Sponsors
Regional Hospital Holstebro
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy males and females * age 18-45 * BMI range 18,5-30,0 kg/m2
Exclusion criteria
* hypertension (i.e. ambulatory BP \> 130 mmHg systolic or/and \> 80 mmHg diastolic) * history or clinical significant signs of heart, lung, liver, kidney, endocrine, brain or neoplastic * disease. * alcohol abuse * drug abuse * smoking * pregnancy or nursing * blood donation within a month prior to examination * medical treatment apart from oral contraception abnormal blood samples, -ECG and -urine dipstick, drug abuse, alcohol abuse, pregnancy, medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| urinary biomarkers | baseline, 0 hours and 1.5 hours after intervention | Urinary excretion of epithelial sodium channels (ENaC), Sodium-potassium-2chloride transporters (NKCC2) and aquaporin2 channels (AQP2) before, during and after fluid infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| vaso active hormones | baseline, 0 hours and 1.5 hours after intervention | plasma concentrations of: renin, Angiotensin II, aldosterone, Vasopressin, ANP and BNP |
| central blood pressure | baseline, 0 hours and 1.5 hours after intervention | measured by applanation-tonometry |
| intracellular (ICV)- and extracellular volume (ECV) | baseline, 0 hours and 1.5 hours after intervention | change in ICV and EVC from baseline and after intervention measured in liters by body composition monitor (BCM) |
Countries
Denmark
Outcome results
None listed