Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients

Abstract

Vasopressin is one of the key regulators of the body's water and solute balance. When this balance is pathologically disturbed, determination of serum vasopressin concentrations might be a helpful tool for guiding therapy. However, due to its instability and considerable association to platelets, reliable measurement of circulating vasopressin is difficult to achieve, if at all. In search of a more robust way for quantifying vasopressin release, we identified copeptin, a glycopeptide with unknown function, as an alternative diagnostic target. Since copeptin is derived from the same precursor peptide as vasopressin, released amounts of copeptin should mirror those of vasopressin. With a newly developed sensitive sandwich immunoassay, we detected strongly elevated concentrations of fully processed copeptin in serum of septic shock patients. The magnitude of elevation and the high stability of copeptin in serum and plasma indicate that copeptin measurement is not affected by the problems, which are associated with the direct measurement of vasopressin, and thus is apparently suitable to indirectly determine the release of vasopressin.

Introduction

Vasopressin (also known as antidiuretic hormone) is a nonapeptide, which is released from the neurohypophysis into the bloodstream in order to promote water conservation by the kidney, and thereby contributes to the regulation of osmotic and cardiovascular homeostasis [23]. Recently, vasopressin has been investigated as a supplementary vasopressor agent in the treatment of septic shock, where endogenous levels of vasopressin apparently decline during the progression of shock [15], [18]. The measurement of endogenous vasopressin levels in plasma could be a useful tool to guide therapy in pathologies where osmotic and cardiovascular homeostasis are dysregulated [20]. However, serious concerns exist about the methodologic reliability of plasma vasopressin measurement, because vasopressin is known to be unstable, largely attached to platelets and rapidly cleared [11], [19], [21].

Vasopressin is derived from a larger precursor peptide along with two other peptides, neurophysin II and copeptin (Fig. 1) [7]. Neurophysin II has a complex structure and is associated with vasopressin, at least under acidic conditions [17]. Copeptin is a 39 amino acid glycopeptide of unknown function in the circulation [9], [24].

Here, we report on the immunometric quantification of copeptin in human serum and plasma as an alternative to direct vasopressin measurement. Since copeptin is initially produced in equimolar amounts to vasopressin, released amounts of copeptin should represent those of vasopressin.