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.

Keywords: Copeptins; Diagnosis; Hypertonic saline solution; Hyponatremia; Treatment outcome.

Figure 1.. Study population algorithm.

ITT, intention to treat; PP, per protocol; SALSA, a randomized clinical trial to evaluate the efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with symptomatic hyponatremia.

Figure 2.. Box plot for copeptin levels (A) and copeptin-to-urine Na × 100 (B) according to etiologies of hyponatremia.

ECF, extracellular fluid; SIAD, syndrome of inappropriate antidiuresis. ^*p < 0.005, compared with decreased ECF due to non-renal Na loss (Kruskal-Wallis test and Bonferroni post hoc test).

Figure 3.. Area under receiver operating characteristics curve for insufficient effective arterial blood volume (secondary copeptin release).

Figure 4.. Outcomes within 6 hours (A) and 24 hours (B) stratified by copeptin level at baseline (below/above median).

Figure 5.. Outcomes within 24 to 48 hours stratified by copeptin level at 24 hours after treatment (below/above median).