Urine Electrolyte to Predict Treatment Failure of Fluid Restriction in Syndrome of Inappropriate Antidiuresis: A Prospective Multicenter Study.

Background: The syndrome of inappropriate antidiuresis (SIAD) is a common cause of hyponatremia in hospitalized patients, with fluid restriction (FR) as the first-line treatment. However, up to 50% of patients fail to respond to FR, highlighting the need for reliable predictors of treatment failure. Therefore, this study aimed to evaluate the predictive performance of urinary biomarkers, including the Furst equation (the ratio of the sum of urinary sodium and potassium concentrations to plasma sodium), urine osmolality, and urine output, in identifying non-responders to FR.

Methods: This prospective multicenter cohort study was conducted at two medical centers in Thailand from September 2022 to June 2024 and included 79 hospitalized patients with SIAD. Response to FR was defined as an increase in serum sodium level of ≥3 mEq/L by Day 4, with no decrease in serum sodium levels at any point during the FR period. Predictive performance was assessed using sensitivity, specificity, and area under the curve (AUC) for each biomarker.Multivariable logistic regression analysis incorporating all urinary biomarkers was also performed.

Results: Overall, 59% of patients failed to respond to FR by day 4, and adherence to FR was modest (72%). The Furst equation demonstrated the best predictive performance, with an optimal cut-off of 0.86 (sensitivity: 55.3%, specificity: 70.2%, AUC: 0.65). Combining the Furst equation with urine osmolality and urine output improved specificity to 91.0%, although sensitivity decreased to 32.3%. A multivariable logistic regression model achieved similar discrimination (AUC: 0.67) compared to the Furst equation alone.

Conclusions: Although the Furst equation can identify non-responders to FR, its predictive performance is limited. Our findings suggest that other urinary biomarkers beyond the Furst equation may not improve overall predictive accuracy for predicting non-response to FR. These findings highlight the need for more effective predictive tools. Further studies are warranted to validate these results and optimize treatment strategies for SIAD.