Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin.

BACKGROUND Arginine vasopressin (AVP) is a key regulator of water balance, but its instability makes reliable measurement difficult and precludes routine use. We present a method for quantifying AVP release by use of copeptin, a glycopeptide comprising the C-terminal part of the AVP prohormone. METHODS We measured copeptin in 50-microL serum and plasma samples from healthy individuals and from critically ill patients with sepsis. Our sandwich immunoluminometric assay used 2 polyclonal antibodies to amino acids 132-164 of pre-provasopressin. RESULTS The assay yielded results within 3 h. The analytical detection limit was 1.7 pmol/L, and the interlaboratory CV was <20% for values >2.25 pmol/L. The assay was linear on dilution of the analyte. Ex vivo copeptin stability (<20% loss of analyte) for at least 7 days at room temperature and 14 days at 4 degrees C was shown for serum and EDTA-, heparin-, and citrate plasma. Copeptin (median, 4.2 pmol/L; range, 1-13.8 pmol/L) was detectable in 97.5% of 359 healthy individuals and was not associated with age. Median concentrations were considerably higher in men than women, increased significantly after exercise, and were influenced by fasting and water load. Copeptin was significantly (P <0.001) increased in 60 critically ill patients with sepsis (median, 79.5 pmol/L; range, 10.6-228.0 pmol/L). The correlation between copeptin and AVP for 110 samples was r = 0.78 (P <0.0001). CONCLUSIONS Copeptin is stable for days after blood withdrawal and can be quickly and easily measured. The copeptin assay may be a useful alternative to direct measurement of AVP concentration.

[1]  K. Turksen,et al.  Isolation and characterization , 2006 .

[2]  J. Struck,et al.  Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients , 2005, Peptides.

[3]  S. Jordan,et al.  Intensive care in adults with congenital heart disease: cost implications of a changing patient population , 2005, Critical Care.

[4]  J. Struck,et al.  Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study , 2004, Critical care.

[5]  Claude D Martin,et al.  Clinical review: Vasopressin and terlipressin in septic shock patients , 2004, Critical care.

[6]  R. MacLaren,et al.  The Role of Vasopressin in Vasodilatory Septic Shock , 2004, Pharmacotherapy.

[7]  E. Breslow,et al.  Properties of human vasopressin precursor constructs: inefficient monomer folding in the absence of copeptin as a potential contributor to diabetes insipidus. , 2004, Biochemistry.

[8]  P. Factor,et al.  Role of vasopressin in the management of septic shock , 2004, Intensive Care Medicine.

[9]  T. Mueller,et al.  Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[10]  J. Burbach,et al.  Structure–Function Relationships of the Vasopressin Prohormone Domains , 1998, Cellular and Molecular Neurobiology.

[11]  J. Struck,et al.  Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. , 2004, Clinical chemistry.

[12]  H. Ruskoaho Cardiac hormones as diagnostic tools in heart failure. , 2003, Endocrine reviews.

[13]  M. Dünser,et al.  Arginine Vasopressin in Advanced Vasodilatory Shock: A Prospective, Randomized, Controlled Study , 2003, Circulation.

[14]  J. Vincent Endocrine support in the critically ill. , 2002, Critical care medicine.

[15]  G. Singh Ranger The physiology and emerging roles of antidiuretic hormone. , 2002, International journal of clinical practice.

[16]  B. Lindahl,et al.  Usefulness of plasma N-terminal proatrial natriuretic peptide (proANP) as an early predictor of outcome in unstable angina pectoris or non-ST-elevation acute myocardial infarction. , 2002, The American journal of cardiology.

[17]  G. Robertson Antidiuretic hormone. Normal and disordered function. , 2001, Endocrinology and metabolism clinics of North America.

[18]  W. Abraham,et al.  Hormones and hemodynamics in heart failure. , 1999, The New England journal of medicine.

[19]  F. Waldhauser,et al.  Improved extraction procedure and RIA for determination of arginine8-vasopressin in plasma: role of premeasurement sample treatment and reference values in children. , 1999, Clinical chemistry.

[20]  H. Bruining,et al.  Vasopressin deficiency contributes to the vasodilation of septic shock. , 1998, Circulation.

[21]  Robertson Gl The use of vasopressin assays in physiology and pathophysiology. , 1994 .

[22]  W. Abraham,et al.  Vasopressin in pathophysiological states. , 1994, Seminars in nephrology.

[23]  G. Robertson The use of vasopressin assays in physiology and pathophysiology. , 1994, Seminars in nephrology.

[24]  J. E. Carceller American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis , 1992, Critical care medicine.

[25]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[26]  W. North Biosynthesis of Vasopressin and Neurophysins , 1987 .

[27]  D. Gash,et al.  Vasopressin : principles and properties , 1987 .

[28]  Robertson Gl Thirst and vasopressin function in normal and disordered states of water balance. , 1983 .

[29]  R. Cody,et al.  Plasma and Platelet Vasopressin in Essential Hypertension and Congestive Heart Failure , 1983, Hypertension.

[30]  G. Robertson Thirst and vasopressin function in normal and disordered states of water balance. , 1983, The Journal of laboratory and clinical medicine.

[31]  D. Smyth,et al.  A new glycopeptide in pig, ox and sheep pituitary. , 1979, Biochemical and biophysical research communications.

[32]  G. Robertson,et al.  Development and clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma. , 1973, The Journal of clinical investigation.

[33]  D. A. Holwerda A glycopeptide from the posterior lobe of pig pituitaries. 2. Primary structure. , 1972, European journal of biochemistry.

[34]  D. A. Holwerda A glycopeptide from the posterior lobe of pig pituitaries. I. Isolation and characterization. , 1972, European journal of biochemistry.

[35]  D. Seligson,et al.  Clinical Chemistry , 1965, Bulletin de la Societe de chimie biologique.