Can treatment response to SGLT2-inhibitors in syndrome of inappropriate antidiuresis be predicted by copeptin, natriuretic peptides and inflammatory markers?

Purpose: The syndrome of inappropriate antidiuresis (SIAD) is the main cause of hyponatremia and the SGLT2-inhibitor empagliflozin is a promising new treatment option. A biomarker predicting treatment response could optimize treatment success. Materials and methods: Secondary analysis of a trial including 84 hospitalized patients with SIAD-induced hyponatremia. Patients were randomized to four days of treatment with empagliflozin 25 mg/d (n = 43) or placebo (n = 41) with both groups receiving fluid restriction <1000 ml/d. Baseline levels of copeptin, the natriuretic peptides MR-proANP and NT-proBNP and C-reactive protein (CRP) were evaluated as predictors for treatment response defined as absolute sodium change, using linear regression models. Additionally, urinary sodium was assessed as predictor for non-response to fluid restriction alone by constructing the receiver-operating characteristic (ROC) curve. Results: No clinically relevant predictive value for treatment response to empagliflozin could be found for copeptin, MR-proANP, NT-proBNP or CRP. A urinary sodium cut-off of >76 mmol/l led to a specificity of 91.7% [95% confidence interval (CI): 75%, 100%] and sensitivity of 51.9% [33.3%, 70.4%] to predict non-response to fluid restriction alone. Conclusions: Based on our data, no biomarker could be identified as predictor for treatment response to empagliflozin. Urinary sodium was confirmed as a good marker for non-response to fluid restriction in SIAD patients. Clinical trial registration: ClinicalTrials.gov (Number: NCT02874807).