Changes in plasma copeptin, the c-terminal portion of arginine vasopressin during water deprivation and excess in healthy subjects

Context: The measurement of arginine vasopressin ( AVP) is often cumbersome because it is unstable with a short half- life time. AVP is derived from a larger precursor peptide along with the more stable peptide copeptin. Copeptin is the C- terminal part of provasopressin and has been shown to be a useful tool to indicate AVP concentration in critically ill patients. Objective: The objective of the study was to evaluate the clinical usefulness of copeptin as a new marker in disordered states of blood volume and plasma osmolality. Design and Setting: This was a prospective observational study in a university hospital. Participants and Main Outcome Measures: Three techniques with respective control studies were used in 24 healthy adults to produce changes in plasma osmolality and/ or volume: 1) a 28- h water deprivation, 2) a 17- h hypertonic saline infusion combined with thirsting, and 3) a hypotonic saline infusion with iv desmopressin administration during free water intake. Results: Water deprivation produced a weight loss of 1.7 kg, an increase in plasma osmolality to 294.8 +/- 4.3 mosmol/ kg, and an increase of copeptin from 4.6 +/- 1.7 pmol/ liter to 9.2 +/- 5.2 pmol/ liter ( P < 0.0001). During hypertonic saline infusion and thirsting with a raise of plasma osmolality to 296.1 +/- 3.4 mosmol/ kg, copeptin increased from 4.9 +/- 3.0 pmol/ liter to 19.9 +/- 4.8 pmol/ liter ( P < 0.0001). Conversely, during hypotonic saline infusion, plasma osmolality decreased to 271.3 +/- 4.1 mosmol/ kg, and copeptin decreased from 6.2 +/- 2.4 pmol/ liter to 2.4 +/- 2.1 pmol/ liter ( P < 0.01). Conclusion: Copeptin shows identical changes during disordered water states as previously shown for AVP. It might be a reliable marker of AVP secretion and substitute for the measurement of circulating AVP levels in clinical routine.