Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics

Background: The syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hyponatremia. Its diagnosis requires decreased serum osmolality, inappropriately diluted urine (e. g. > 100 mOsm/kg), clinical euvolemia, and a urinary sodium (Na) excretion (U-Na) more than 30 mmol/liter. However, in hyponatremic patients taking diuretics, this definition is unreliable due to the natriuretic effect of diuretics. Here, we examined the diagnostic potential of alternative laboratory measurements to diagnose SIAD, regardless of the use of diuretics. Methods: A total of 86 consecutive hyponatremic patients (serum Na < 130 mmol/liter) was classified based on their history, clinical evaluation, osmolality, and saline response to isotonic saline into a SIAD and a non-SIAD group. U-Na, serum urate concentration, and fractional excretion (FE) of Na, urea, and uric acid (UA) were measured in all subjects. The accuracy to diagnose SIAD was assessed using receiver operating characteristic analysis. Results: A total of 31 patients (36%) had a diagnosis of SIAD, and 55 (64%) were classified as non-SIAD. There were 57 patients (68%) who were on diuretics (15 in the SIAD group, 42 in the non-SIAD group). In the absence of diuretic therapy, SIAD was accurately diagnosed using U-Na (area under the receiver operating characteristic curve 0.96; 0.92-1.02). However, in patients on diuretics, the diagnosis was unreliable (area under the curve 0.85; 0.73-0.97). There, FE-UA performed best compared with all other markers tested (area under the curve 0.96; 0.92-1.12), resulting in a positive predictive value of 100% if a cutoff value of 12% was used. Conclusion: FE-UA allows the diagnosis of SIAD with excellent specificity. Combining the information on U-Na and FE-UA leads to a very high diagnostic accuracy in hyponatremic patients with and without diuretic treatment.