Hyponatremia (blood sodium <135 mmol/l) is the most frequent electrolyte and fluid disturbance with a prevalence up to 30% in hospitalized patients. The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD) which is also the main etiology of hyponatremia overall. Urea osmotic diuresis has been reported to cause hypernatremia in critically ill patients in intensive care unit (ICU), showing that urea can influence sodium levels. Increasing solute intake with oral urea represents a valid treatment approach to increase urine volume and solute free water clearance through osmotic diuresis and reduction of urinary sodium excretion in SIAD. In Switzerland, urea is a medical food prepared as a compounding agent by pharmacies. Endogenous proteins and dietary protein are metabolized into nitrogen which is metabolized to soluble excretable urea by the liver. Protein intake could represent an osmotic relevant source of urea. The Jone's factor of 6,25 is commonly used to convert nitrogen to protein equivalent, assuming an average nitrogen content of 16% in protein (100g protein / 6,5 = 16g nitrogen).~Urea (CH₄N₂O) contains 46,6% nitrogen (atomic weight of nitrogen = 14 g/mol, atomic weight of urea = 60,1 g/mol). Using these ratios, 30g urea would correspond to 14g nitrogen and 87,5g protein. In this study, a 90g protein supplementation will be used, which corresponds roughly to 30g urea, in form of a daily intake of protein powder (Whey Protein®, foodspring GmbH, Germany or Clear Whey Isolate®, MyProtein THG Company, United Kingdom), which is freely marketed as food in Switzerland. Both interventional products are not considered as drugs.~Patients with a plasma sodium concentration <125 mmol/L are at increased risk for overcorrection, i.e., an increase in plasma sodium levels >10 mmol/L in the first 24 hours of treatment. An additional visit will be planned on the second day of treatment in order to recognize rise over this limit and initiate relowering counteractions, which will include the skip of the second powder intake and oral fluid intake.~This study is to analyze whether protein supplementation can increase plasma sodium levels in patients with SIAD by increasing urinary urea excretion.
This study aims to investigate whether a 7-day dietary high protein supplementation of 90 grams per day increases plasma sodium levels in hyponatremic patients with chronic SIAD.~Enrolled patients will receive first dietary high protein supplementation for one week. After a wash-out phase of at least one week, the patients will receive oral urea for another week.