Chloride and Potassium Assessment Is a Helpful Tool for Differential Diagnosis of Thiazide-Associated Hyponatremia

CONTEXT: Differential diagnosis of thiazide-associated hyponatremia (TAH) is challenging. Patients can either have volume depletion or a syndrome of inappropriate antidiuresis (SIAD)-like presentation. OBJECTIVE: To evaluate the impact of the simplified apparent strong ion difference in serum (aSID; sodium + potassium − chloride) as well as the urine chloride and potassium score (ChU; chloride − potassium in urine) in the differential diagnosis of TAH, in addition to assessment of fractional uric acid excretion (FUA). METHODS: Post hoc analysis of prospectively collected data from June 2011 to August 2013 from 98 hospitalized patients with TAH < 125 mmol/L enrolled at University Hospital Basel and University Medical Clinic Aarau, Switzerland. Patients were categorized according to treatment response in volume-depleted TAH requiring volume substitution or SIAD-like TAH requiring fluid restriction. We computed sensitivity analyses with ROC curves for positive predictive value (PPV) and negative predictive value (NPV) of aSID, ChU, and FUA in differential diagnosis of TAH. RESULTS: An aSID > 42 mmol/L had a PPV of 79.1% in identifying patients with volume-depleted TAH, whereas a value < 39 mmol/L excluded it with a NPV of 76.5%. In patients for whom aSID was inconclusive, a ChU < 15 mmol/L had a PPV of 100% and a NPV of 83.3%, whereas FUA < 12% had a PPV of 85.7% and a NPV of 64.3% in identifying patients with volume-depleted TAH. CONCLUSION: In patients with TAH, assessment of aSID, potassium, and chloride in urine can help identifying patients with volume-depleted TAH requiring fluid substitution vs patients with SIAD-like TAH requiring fluid restriction.