Overview
The goal of this study is to assess the impact of protein supplementation on hyponatremia caused by the syndrome of inappropriate antidiuresis during hospitalization.
Description
Hyponatremia (plasma sodium <135 mmol/L) is the most common electrolyte disorder, affecting up to 30% of hospitalized patients. Chronic hyponatremia (>48 hours) is linked to longer hospital stays, higher costs, increased mortality, and morbidity (e.g., falls, fractures, cognitive deficits). The most common cause of euvolemic hyponatremia is syndrome of inappropriate antidiuresis (SIAD), characterized by excessive water retention due to dysregulated vasopressin activity. Treatment options include fluid restriction or increasing water excretion with AVP antagonists, SGLT2 inhibitors, or oral urea.
A recent trial showed that protein supplementation can induce osmotic diuresis and raise sodium levels similarly to oral urea, with better tolerability. Since protein supplementation is often used in hospitalized patients with malnutrition, this study aims to compare its acceptability to fluid restriction in hospitalized SIAD patients. This head-to-head superiority trial will randomize patients to receive either 80 g of dietary protein daily or fluid restriction (1000 mL/day) for up to 5 days. The hypothesis is that protein supplementation is significantly more acceptable to patients than fluid restriction, ultimately improving treatment outcomes.
Eligibility
Inclusion Criteria:
- Adult patients with confirmed SIAD during the hospital stay or at screening, defined
- by
- 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, celiac disease, milk protein allergy, soy allergy, nuts allergy, or hypersensitivity to components of the protein supplement.
- Inborn metabolic disorders affecting carbohydrate, lipid, or protein metabolism.
- Severe symptomatic hyponatremia requiring 3% NaCl or intensive care.
- Type 1 diabetes or uncontrolled type 2 diabetes (HbA1c >8.0%).
- Uncontrolled severe hypothyroidism or adrenal insufficiency.
- eGFR <60 mL/min/1.73 m² (KDIGO G3-5) or end-stage renal disease.
- Severe hepatic impairment or advanced symptomatic liver disease.
- New (within the last five days) treatment with diuretics, SGLT2 inhibitors, lithium, urea, vaptans
- Pregnancy, breastfeeding, or plans to become pregnant during the study.
- End-of-life care, current participation in another intervention study, or inability to give informed consent or follow study procedures.