Association between copeptin levels and treatment responses to hypertonic saline infusion in patients with symptomatic hyponatremia: a prospective cohort study

Abstract

Background: Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients. Methods: We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24-48 hours and copeptin levels at baseline/24 hours were analyzed. Results: Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02). Conclusion:There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.

Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia

“…There were no RCTs or meta-analyses exploring the value of copeptin in patients with hyponatremia. In the present guideline, one observational study published after 2015 was added and discussed [33].…”

A novel role of copeptin as a biomarker for the prediction of treatment response in hyponatremia

“…In the current study, Go et al [7] also investigated the usefulness of copeptin for differentiating etiologies of hyponatremia. The participants were classified into five categories, based on the patient's history, physical examination, and laboratory test results: (1) decreased extracellular fluid (ECF) volume due to renal Na loss (e.g., diuretics, especially thiazides); (2) decreased ECF volume due to nonrenal sodium loss (e.g., gastrointestinal Na loss or third spacing: vomiting, diarrhea, or malnutrition); (3) increased ECF volume (e.g., heart failure, liver cirrhosis, and nephrotic syndrome); (4) normal ECF volume with adrenal insufficiency; and (5) normal ECF volume fulfilling the essential criteria for SIAD.…”

“…In this regard, Go et al [7] conducted analyses from a total of 100 participants in a prospective cohort to investigate the role of copeptin as a biomarker for the diagnosis and prognosis in hypoosmolar disorders. All participants were defined as having symptomatic hyponatremia (corrected serum sodium of ≤125 mmol/L) and were treated with hy-pertonic saline, where mean serum sodium and median copeptin levels were 117.9 and 16.9 pmol/L, respectively.…”

“…In summary, Go et al [7] suggested a novel role of copeptin as a biomarker for the prediction of treatment response in hyponatremia. The authors demonstrated that low copeptin levels at the baseline are associated with a significantly higher target correction rate in 6 and 24 hours after hypertonic saline treatment start, and that low copeptin levels at 24-hour after hypertonic saline treatment is associated with a significantly higher overcorrection rate in the next 24 hours.…”

“…Interpretation of plasma copeptin level during hypertonic saline treatment of hyponatremic patients, suggested by Go et al[7] Increased risk of overcorrection by the same amount of hypertonic saline • 24-hour after hypertonic saline treatment: Less excretion of free water → Decreased risk of overcorrection by the same amount of hypertonic salineNote that low and high copeptin levels indicate below and above median copeptin level (16.9 pmol/L), respectively.…”