Abstract：
Copeptin is a 39-amino-acid long glycosylated peptide with a leucine-rich core segment in the C-terminal part of pre-pro-vasopressin. It exhibits a rapid response comparable to arginine vasopressin (AVP) in response to osmotic, hemodynamic, and nonspecific stress-related stimuli. This similarity can be attributed to equimolar production of copeptin alongside AVP. However, there are markedly different decay kinetics for both peptides, with an estimated initial half-life of copeptin being approximately two times longer than that of AVP. Like AVP, copeptin correlates strongly over a wide osmolality range in healthy individuals, making it a useful alternative to AVP measurement. While copeptin does not appear to be significantly affected by food intake, small amounts of oral fluid intake may result in a significant decrease in copeptin levels. Compared to AVP, copeptin is considerably more stable in vitro. An automated immunofluorescent assay is now available and has been used in recent landmark trials. However, separate validation studies are required before copeptin thresholds from these studies are applied to other assays. The biological variation of copeptin in presumably healthy subjects has been recently reported, which could assist in defining analytical performance specifications for this measurand. An established diagnostic utility of copeptin is in the investigation of polyuria-polydipsia syndrome and copeptin-based testing protocols have been explored in recent years. A single baseline plasma copeptin >21.4 pmol/L differentiates AVP resistance (formerly known as nephrogenic diabetes insipidus) from other causes with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. In a recent study among adult patients with polyuria-polydipsia syndrome, AVP deficiency (formerly known as central diabetes insipidus) was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. Glucagon-stimulated copeptin has been proposed as a potentially safe and precise test in the investigation of polyuria-polydipsia syndrome. Furthermore, copeptin could reliably identify those with AVP deficiency among patients with severe hypernatremia, though its diagnostic utility is reportedly limited in the differential diagnosis of profound hyponatremia. Copeptin measurement may be a useful tool for early goal-directed management of post-operative AVP deficiency. Additionally, the potential prognostic utility of copeptin has been explored in other diseases. There is an interest in examining the role of the AVP system (with copeptin as a marker) in the pathogenesis of insulin resistance and diabetes mellitus. Copeptin has been found to be independently associated with an increased risk of incident stroke and cardiovascular disease mortality in men with diabetes mellitus. Increased levels of copeptin have been reported to be independently predictive of a decline in estimated glomerular filtration rate and a greater risk of new-onset chronic kidney disease. Furthermore, copeptin is associated with disease severity in patients with autosomal dominant polycystic kidney disease. Copeptin predicts the development of coronary artery disease and cardiovascular mortality in the older population. Moreover, the predictive value of copeptin was found to be comparable with that of N-terminal pro-brain natriuretic peptide for all-cause mortality in patients with heart failure. Whether the measurement of copeptin in these conditions alters clinical management remains to be demonstrated in future studies.
摘要：
Copeptin是一种39个氨基酸长的糖基化肽，在前加压素的C末端部分具有富含亮氨酸的核心片段。它表现出与精氨酸加压素（AVP）相当的快速反应，血液动力学,和非特异性应激相关刺激。这种相似性可以归因于和肽素与AVP的等摩尔产生。然而,两种肽都有明显不同的衰变动力学，估计和肽素的初始半衰期大约是AVP的两倍。像AVP一样,在健康个体中，和肽素在广泛的渗透压范围内密切相关，使其成为一个有用的替代AVP测量。虽然和肽素似乎没有受到食物摄入的显著影响，少量口服液体摄入可能导致和肽素水平显著下降.与AVP相比，和肽素在体外相当稳定。现在可以使用自动免疫荧光测定法，并已在最近的里程碑式试验中使用。然而,在将来自这些研究的和肽素阈值应用于其他检测之前,需要进行单独的验证研究.最近报道了和肽素在假定健康受试者中的生物学变异，这可以帮助定义该被测量的分析性能规格。copeptin的既定诊断效用是在多尿-多饮综合征的研究中，近年来已经探索了基于copeptin的检测方案。单一基线血浆和肽素>21.4pmol/L可将AVP抵抗（以前称为肾性尿崩症）与其他原因区分开来，敏感性和特异性为100％。在这种情况下，没有必要进行缺水测试。在最近一项针对多尿多饮综合征的成年患者的研究中，高渗盐水刺激的和肽素比精氨酸刺激的和肽素更准确地诊断出AVP缺乏症（以前称为中枢尿崩症）。在多尿多饮综合征的研究中，胰高血糖素刺激的和肽素被认为是一种潜在的安全和精确的测试。此外，copeptin可以可靠地识别严重高钠血症患者中AVP缺乏的患者，尽管据报道，其诊断效用在深度低钠血症的鉴别诊断中受到限制。Copeptin测量可能是术后AVP缺陷的早期目标导向管理的有用工具。此外,已经探索了和肽素在其他疾病中的潜在预后效用。人们对检查AVP系统（以和肽素作为标记）在胰岛素抵抗和糖尿病的发病机理中的作用感兴趣。已发现，在患有糖尿病的男性中，和肽素与卒中和心血管疾病死亡率的风险增加独立相关。据报道，和肽素水平的增加可以独立预测估计的肾小球滤过率下降和新发慢性肾病的风险。此外，copeptin与常染色体显性多囊肾病患者的疾病严重程度相关。Copeptin预测老年人冠状动脉疾病和心血管疾病死亡率的发展。此外，发现和肽素与N末端脑钠肽前体对心力衰竭患者全因死亡率的预测价值相当.在这些情况下，和肽素的测量是否会改变临床管理，还有待在未来的研究中证明。
