High urine osmolality and elevated urine sodium predict early nonresponse to fluid restriction in patients with the syndrome of inappropriate antidiuresis

Abstract Introduction Fluid restriction is the current first‐line therapy for hyponatremia induced by the syndrome of inappropriate antidiuresis (SIAD), yet up to 50% of patients do not achieve an adequate plasma sodium correction. Reported predictors of nonresponse include urine osmolality >500 mOsm/kg, the Furst ratio >1 [(UNa + UK)/(PNa)], urine sodium >130 mmol/L, and plasma urea >5 mmol/L. This study aimed to validate these cutoffs in an independent cohort. Methods This is a predefined secondary analysis of a randomized, controlled, prospective, and multicenter hyponatremia trial (plasma sodium <130 mmol/L). Response to fluid restriction was defined as an increase in plasma sodium of >3 mmol/L within the first 24 h. Results Of 839 patients with SIAD, 229 were treated with fluid restriction within the first 24 h and had complete laboratory data. Among these patients, 86 (38%) were classified as responders and 143 (62%) as nonresponders. Higher urine osmolality ( p = 0.015) and higher plasma sodium levels ( p < 0.001) were independently associated with nonresponse in multivariable logistic regression analysis. Urine osmolality >500 mOsm/kg had a specificity of 78% (positive likelihood ratio (LR+) 1.68), whereas urine sodium >130 mmol/L had a specificity of 97% (LR+ 3.81). The combination of both cutoffs markedly improved discriminatory performance (LR+ 9.62, positive predictive value 0.94). Conclusion The present study validated urine osmolality >500 mOsm/kg and urine sodium >130 mmol/L as cutoffs for predicting nonresponse to fluid restriction in patients with SIAD. Combining both cutoffs identifies patients at high risk of nonresponse, in whom early initiation of second‐line therapy should be strongly considered.