Endocrine Abstracts

Introduction: The syndrome of inappropriate antidiuresis (SIAD) is the most common cause of euvolemic hyponatremia. Besides fluid restriction, increasing free water clearance is an effective treatment approach that can be achieved through osmotic diuresis by administering oral urea. Dietary proteins are metabolized into soluble excretable urea by the liver. We hypothesized that dietary protein could increase free water clearance through urea-induced osmotic diuresis and therefore aimed to investigate the effect of high-protein supplementation on plasma sodium levels in outpatients with chronic SIAD.

Methods: This is an interim analysis of a monocentric open-label proof-of-concept trial conducted at the University Hospital of Basel in Switzerland since October 2021. Adult outpatients with chronic SIAD of any etiology were eligible. Patients received 90 g protein daily for 7 days in the form of protein powder dissolved in a maximum of 1L of liquid of choice. After a wash-out period of at least a week, patients received 30 g of oral urea daily for 7 days. Patients were asked to keep their baseline fluid intake unchanged throughout the study. The primary endpoint was the increase in sodium levels from baseline to the end of the 7-day protein supplementation.

Results: Fourteen patients, 11 females and 3 males, with chronic SIAD were included. Median [IQR] age was 68 [61, 80] and median duration of hyponatremia was 21 months [3, 59]. At baseline, median plasma sodium concentration was 130 mmol/l [128, 133]. Eight patients had mild hyponatremia (130-134 mmol/l), 4 had moderate hyponatremia (125-129 mmol/l), and 2 patients had profound hyponatremia (<125 mmol/l). After 7 days of 90 g daily protein supplementation (n=14), sodium levels increased by a median of 3.5 mmol/l [0.5, 5.8], blood urea nitrogen increased by a median of 4.3 mmol/l [1.7, 5.1] and urinary urea corrected for urine creatinine increased by a median of 25.3 mmol/mmol [15.6, 31.2]. After 7 days of oral urea (n=8), sodium levels increased by a median of 2 mmol/l [1, 3], blood urea nitrogen increased by a median of 8.5 mmol/l [3.8, 10.2] and urinary urea corrected for urine creatinine increased by a median of 31 mmol/mmol [21.1, 39.8].

Conclusion: This analysis suggests that high-protein supplementation with protein powder increases plasma sodium levels in patients with chronic SIAD. The increase in urea concentration in both plasma and urine upon protein supplementation is comparable to the increase upon oral urea administration, which supports protein-induced ureagenesis to be the underlying mechanism of action.