title: Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock.
abstract: Arginine vasopressin (AVP) levels are increased in hemorrhagic and septic shock. Measurement of AVP levels has limitations due to its short half-life and cumbersome detection method. Copeptin is a more stable peptide derived from the same precursor molecule. We evaluated the plasma copeptin concentration in two independent studies: first, in an experimental baboon model of hemorrhagic shock, and second, in a prospective observational study of 101 consecutive critically ill patients at a university hospital. Copeptin was measured with a newly developed sandwich immunoassay using two polyclonal antibodies to the C-terminal region (amino acid sequence 132-164) of pre-pro-AVP. Copeptin concentrations in hemorrhagic shock increased markedly from median (range) of 7.5 [2.7-13) to 269 pM (241-456 pM). After reperfusion, copeptin levels dropped within hours to a plateau of 27 pM (15-78 pM). In the critically ill patient cohort, copeptin values increased significantly with the severity of the disease and were in patients without sepsis [27.6 pM [2.3-297 pM]), in sepsis [50.0 pM [8.5-268 pM]), in severe sepsis [73.6 pM [15.3-317 pM]), and in septic shock [171.5 pM (35.1-504 pM] compared with 4.1 pM (1.0-13.8 pM) in healthy controls (P for all vs. controls <0.001). On admission, circulating copeptin levels were higher in nonsurvivors (171.5 pM, 46.5-504.0 pM) as compared with survivors (86.8 pM, 8.5-386.0 pM; P = 0.01). Copeptin levels correlated with basal cortisol levels (r = 0.42; P < 0.001) and osmolality (r = 0.42; P < 0.001). In a logistic regression model including other covariates besides copeptin (e.g., determinants of fluid status) on survival, serum copeptin levels were the only independent significant predictor of outcome (P = 0.03). Copeptin concentrations are elevated in hemorrhagic and septic shock. Copeptin was higher on admission in nonsurvivors as compared with survivors, suggesting copeptin as a prognostic marker in sepsis. The availability of a reliable assay for the measurement of AVP release can also prove useful for the assessment of fluid and osmosis status in various diseases.
authors.affiliation: Research Department, B R A H M S AG, Biotechnology Centre Hennigsdorf/Berlin, Neuendorfstrasse 25, D-16761 Hennigsdorf bei Berlin, Germany. a.morgenthaler@brahms.de
authors.forename: Nils G
authors.initials: NG
authors.lastname: Morgenthaler
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006020:Glycopeptides / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D048549:Papio ursinus / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*
chemical_list: D006020:Glycopeptides; D011498:Protein Precursors; C048197:copeptins; D001127:Arginine Vasopressin