Protein Supplementation in Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis

Inclusion Criteria:

• Adult patients with confirmed SIAD during the hospital stay or at screening, definedby:

• Plasma sodium concentration <135 mmol/L

• Plasma osmolality <300 mOsm/kg

• Urine osmolality >100 mOsm/kg

• Urine sodium concentration >30 mmol/L

• Clinical euvolemia (no signs of hypovolemia or hypervolemia)

Exclusion Criteria:

• Lactose intolerance, milk protein allergy, soy allergy, nuts allergy, orhypersensitivity to components of the protein supplement.

• Inborn metabolic disorders affecting carbohydrate, lipid, or protein metabolism.

• Severe symptomatic hyponatremia requiring 3% NaCl or intensive care.

• New (within the last five days) treatment with SGLT2 inhibitors, vaptans or oralurea

• Uncontrolled severe hypothyroidism (untreated)

• Uncontrolled adrenal insufficiency (morning cortisol <150nmol/l)

• eGFR <45 mL/min/1.73 m² (KDIGO G3b-5) or end-stage renal disease (dialysis)

• Severe hepatic impairment or advanced symptomatic liver disease defined as past orcurrent hepatic encephalopathy, liver cirrhosis Child C, or decompensated (bleeding,jaundice, hepatorenal syndrome)

• Pregnancy, breastfeeding, or plans to become pregnant during the study.

• End-of-life care

• Lack of capacity or other reasons preventing from giving informed consent orfollowing study procedures (e.g., due to language problems, psychological disorders,dementia, etc.)

• Treatment with thiazid diuretic (must be stopped at least 48 hours before inclusion)

Post-randomization Exclusion Criteria:

• Type 1 diabetes or uncontrolled type 2 diabetes (HbA1c >8.0%)