Copeptin in the differential diagnosis of hyponatremia

Background: Treatment of patients with hyponatremia varies widely. Thus, readily available and reliable parameters are needed to guide the appropriate treatment strategy. This study was designed to determine the diagnostic potential of copeptin, the C-terminal part of the vasopressin precursor peptide, as a surrogate of AVP secretion, and to examine its value in the differential diagnosis of hyponatremia. Methods: In this prospective observational study, 106 consecutive hyponatremic patients (serum sodium <130 mmol/L) were classified based on their history, clinical evaluation, laboratory tests, and saline response to isotonic saline. In all patients, as well as in 32 healthy control subjects, plasma copeptin concentration, [copeptin/U-Na] ratio, and standard biochemical parameters were measured and tested for their utility of diagnosing SIAD. Results: Four patients (4%) were diagnosed as primary polydipsia, 9 patients (8%) as diuretic-induced hyponatremia, 42 patients as SIAD (40%), 29 patients as hypovolemic hyponatremia (27%), and 22 patients as hypervolemic hyponatremia (21%). In controls, a close correlation between plasma copeptin and serum sodium (r=0.78, P<0.001) or urine osmolality (r=0.57, P=0.001) was observed. In hyponatremic patients, plasma copeptin levels were significantly higher in hypo- and hypervolemic hyponatremia compared to SIAD (P<0.005, respectively) and primary polydipsia (P<0.001). The [Copeptin/U-Na] ratio differentiated accurately between arterial volume-depleted and normovolemic disorders (area under the ROC curve 0.88, 95%CI 0.81–0.95; P<0.001) resulting in a sensitivity and specificity of 85% and 87% if a cut-off value of 30pmol/mmol was used. The combined information of plasma copeptin <3pmol/L and urine osmolality <200 mOsm/kg correctly diagnosed primary polydipsia in 100% of patients. Conclusion: In hyponatremic patients, plasma copeptin reliably reflects AVP secretion. In these patients, the [Copeptin/U-Na] ratio allows to distinguish accurately between volume-depleted and normovolemic disorders, while the combined information on plasma copeptin and urine osmolality confers a high diagnostic accuracy in the diagnosis of polydipsia.