Reassessing the Role of Copeptin in Emergency Department Admissions for Hypotonic Hyponatremia.

Berton, Alessandro Maria; Varaldo, Emanuele; Zavattaro, Marco; Locatelli, Stefania; Ferrera, Patrizia; Pivetta, Emanuele; Gatti, Filippo; Prencipe, Nunzia et al. · J Clin Endocrinol Metab · 2025

prospective_cohort · Level II

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Abstract

The role of copeptin in assessing hyponatremic patients at emergency department (ED) admission remains debated. This work aimed to assess copeptin's effectiveness in evaluating extracellular fluid (ECF) volume and its predictive value in hyponatremic adults admitted to the medical ED. This work comprises a report from the IPSO-URG, a prospective cohort study with recruitment from June 2018 to August 2019 and 6-month follow-up. The setting is a medical ED of a single tertiary center. Patients included a consecutive sample of 123 adults with hyponatremia confirmed by direct and indirect ion-selective electrode assay after glucose correction. Excluding 33 individuals with missing consent or criteria and 6 without hypotonic hyponatremia, 84 patients were analyzed. Data included symptoms, vital signs, ultrasound, medical history, Charlson Comorbidity Index, and pretreatment blood and urine samples. ECF status was reassessed post discharge by 3 endocrinologists, blinded to copeptin results, who classified cases etiologically and resolved disagreements through discussion. In-hospital and 6-month mortality were recorded. A copeptin-to-urinary sodium (u-Na) ratio less than or equal to 29.5 pmol/mmol increased the likelihood of preserved ECF more than 4-fold (odds ratio 4.28; P = .026), outperforming standard u-Na (area under the curve difference 0.177; P = .013). Copeptin predicted in-hospital mortality (hazard ratio [HR] 1.005), with greater than 60.1 pmol/L as the optimal cutoff (P = .0005). Copeptin (HR 1.005; P = .02), N-terminal prohormone of brain natriuretic peptide (HR 1.004; P = .031), and comorbidity burden (HR 1.207; P = .009) predicted 6-month mortality, with copeptin greater than 13.6 pmol/L indicating a more than 4-fold risk (HR 4.507; P = .0001). Measuring copeptin on ED admission in hypotonic hyponatremia aids diagnosis and mortality prediction. The copeptin/u-Na index more accurately identifies preserved ECF than the standard u-Na cutoff.

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