Effect of protein supplementation on plasma sodium levels in the syndrome of inappropriate antidiuresis: a monocentric, open-label, proof-of-concept study—the TREASURE study

Abstract

Abstract Importance The syndrome of inappropriate antidiuresis (SIAD) can be treated with oral urea; however, compliance is impaired by its poor palatability. Objective To investigate whether dietary proteins could increase plasma sodium levels through urea-induced osmotic diuresis. Design An open-label, proof-of-concept trial. Setting University Hospital of Basel, Switzerland, between October 2021 and February 2023. Participants Outpatients with chronic SIAD. Interventions or exposures Ninety grams of protein daily for 7 days in the form of protein powder, followed by 30 g of oral urea daily for 7 days after a wash-out period of ≥1 week. Main outcomes and measures The increase in sodium levels from baseline to the end of the 7-day protein supplementation. Results Seventeen patients were included. After 7 days of 90 g daily protein supplementation (n = 17), plasma sodium levels increased from 131 (129-133) to 133 (132-137), that is, by a median of 3 mmol L–1 (0-5) (P = .01). Plasma urea levels increased by 3 mmol L–1 (1.7-4.9) (P < .01), and urine urea to creatinine ratio increased by 21.2 mmol mmol–1 (6.2-29.1) (P < .01). After 7 days of 30 g oral urea (n = 10), plasma sodium levels increased from 132 (130-133) to 134 (131-136), that is, by a median of 2 mmol L–1 (1-3) (P = .06). Plasma urea levels increased by 5.8 mmol L–1 (2.7-9.2) (P < .01), and urine urea to creatinine ratio increased by 31.0 mmol mmol–1 (18.7-45.1) (P < .01). Conclusions and relevance Our findings suggest that protein powder increases plasma sodium levels in patients with chronic SIAD through protein-induced ureagenesis and osmotic diuresis. The effects are comparable with oral urea.