While secreted in equimolar concentrations in conjunction with arginine vasopressin (AVP), measured plasma concentrations of copeptin do not correlate strongly with AVP concentrations due to in vivo and in vitro differences in stability. Copeptin is a more stable surrogate biomarker of AVP release. The clinical utility of copeptin of differentiating polyuria and water balance disorders has been demonstrated in a number of studies, when used in conjunction with osmolality and hydration status.

In a prospective clinical study, an algorithm was established based on patients with polyuria-polydipsia syndrome (n=55). A non-water deprived baseline copeptin concentration of 21.4 pmol/L or greater was found to be consistent with the presence of nephrogenic diabetes insipidus (DI). In a described algorithm,(1) patients with a copeptin concentrations of under 21.4 pmol/L and a copeptin cut-off of 4.9 pmol/L after fluid deprivation, was used to distinguish between complete or partial DI (<4.9 pmol/L) and primary polydipsia (> or =4.9 pmol/L).

Central DI may also be differentiated from nephrogenic DI by measuring copeptin during a stimulus for AVP release such as a water deprivation test. Copeptin concentrations obtained in the process of a water deprivation test can be difficult to interpret because of variation in water deprivation protocols. Patients with psychogenic polydipsia will either have a normal response to water deprivation or, in long-standing cases, show a pattern suggestive of mild nephrogenic DI. Expert consultation is recommended in these circumstances.

Although the water-deprivation test is considered the reference standard for the evaluation of DI, measurement of saline stimulated copeptin was shown to be more accurate than the water-deprivation test.(2) In this indirect water deprivation test with a cutoff of 4.9 pmol/L or less indicated central DI while a concentration greater than 4.9 pmol/L indicated primary polydipsia.

An elevated plasma copeptin AVP concentration in a hyponatremic patient may be indicative of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). However, copeptin determination alone is not typically sufficient to distinguish SIADH from other hyponatremic disorders.(3)

Elevations of plasma copeptin in patients with symptoms of heart failure may be prognostic of short- and long-term mortality. In patients with heart failure (HF) following a myocardial infarction, elevations in copeptin are associated with severity of HF and poorer prognosis.(4) In a cohort of patients with class III or IV HF, copeptin concentrations of 40 pmol/L or greater significantly increased the risk of death or need for cardiac transplantation. The combination of elevated copeptin and hyponatremia was an even stronger predictor of heart failure, independent of B-type natriuretic peptide (BNP) and cardiac troponin (cTn) concentrations.(5)