Morgenthaler Nils G, Müller Beat, Struck Joachim, Bergmann Andreas, Redl Heinz, Christ-Crain Mirjam
Research Department, B R A H M S AG, Biotechnology Centre Hennigsdorf/Berlin, Neuendorfstrasse 25, D-16761 Hennigsdorf bei Berlin, Germany.
Shock. 2007 Aug;28(2):219-26. doi: 10.1097/SHK.0b013e318033e5da.
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.
精氨酸加压素（AVP）水平在失血性休克和感染性休克中会升高。由于AVP半衰期短且检测方法繁琐，对其水平的测量存在局限性。 copeptin是一种源自同一前体分子的更稳定的肽。我们在两项独立研究中评估了血浆copeptin浓度：第一项研究是在失血性休克的实验狒狒模型中，第二项研究是在一家大学医院对101例连续的危重症患者进行的前瞻性观察研究。使用针对前体AVP C端区域（氨基酸序列132 - 164）的两种多克隆抗体，通过新开发的夹心免疫测定法测量copeptin。失血性休克时copeptin浓度从中位数（范围）7.5 [2.7 - 13）显著增加至269 pM（241 - 456 pM）。再灌注后，copeptin水平在数小时内降至27 pM（15 - 78 pM）的平台期。在危重症患者队列中，copeptin值随疾病严重程度显著增加，在无脓毒症患者中为[27.6 pM [2.3 - 297 pM]]，脓毒症患者中为[50.0 pM [8.5 - 268 pM]]，严重脓毒症患者中为[73.6 pM [15.3 - 317 pM]]，感染性休克患者中为[171.5 pM（35.1 - 504 pM]，而健康对照者为4.1 pM（1.0 - 13.8 pM）（与所有对照组相比P < 0.001）。入院时，非存活者的循环copeptin水平（171.5 pM，46.5 - 504.0 pM）高于存活者（86.8 pM，8.5 - 386.0 pM；P = 0.01）。copeptin水平与基础皮质醇水平（r = 0.42；P < 0.001）和渗透压（r = 0.42；P < 0.001）相关。在一个包括copeptin之外的其他协变量（如液体状态决定因素）的生存逻辑回归模型中，血清copeptin水平是唯一独立的显著预后预测指标（P = 0.03）。失血性休克和感染性休克时copeptin浓度升高。与存活者相比，非存活者入院时copeptin水平更高，提示copeptin可作为脓毒症的预后标志物。一种用于测量AVP释放的可靠检测方法的可用性也可能对评估各种疾病中的液体和渗透状态有用。
