Copeptin (human)

Arginine Vasopressin (AVP) and copeptin derive from the same precursor molecule. Due to the equimolar secretion, copeptin responds as rapidly as AVP to osmotic, hemodynamic and unspecific stress-related stimuli and both peptides show a very strong correlation. The physiological functions of AVP are homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response. In contrast, the exact function of copeptin remains unknown. Since copeptin, in contrast to AVP, can easily be measured with a sandwich immunoassay, its main function so far that it indirectly indicates the amount of AVP in the circulation. Copeptin has emerged as a useful measure in different diseases. On one hand, through its characteristics as a marker of stress, it provides a unique measure of the individual stress burden. As such, it is a prognostic marker in different acute diseases such as ischemic stroke or myocardial infarction. On the other side, it has emerged as a promising marker in the diagnosis of AVP-dependent fluid disorders. Copeptin reliably differentiates various entities of the polyuria polydipsia syndrome; baseline levels >20 pmol/L without prior fluid deprivation identify patients with nephrogenic diabetes insipidus, whereas levels measured upon osmotic stimulation with hypertonic saline or upon non-osmotic stimulation with arginine differentiate primary polydipsia from central diabetes insipidus. In patients with hyponatremia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, but copeptin levels overlap in all other causes of hyponatremia, limiting its diagnostic use in hyponatremia. Copeptin has also been put forward as predictive marker for autosomal dominant polycystic kidney disease and for diabetes mellitus, but more studies are needed to confirm these findings.

Pregnancy-induced hypertension (PIH) occurs in 6-8% of pregnancies, and increases the risk of many severe obstetric complications. The etiology of PIH has not been fully explained, and hence, treatment is only palliative in nature, and prevention is not fully effective. It has been proposed that PIH development is influenced by the arginine vasopressin pathway, whose surrogate biomarker is copeptin. The aim of this study is a prospective assessment of the relationship between the level of copeptin in pregnant women and the occurrence of PIH, and to identify its usefulness in predicting complications. The study involved a group of 21 pregnant women who developed PIH and 37 women with uncomplicated pregnancies as a control group. Blood samples were collected at the three trimesters of gestation (26 HBD) and then frozen. Copeptin levels [pg/mL] were measured in serum samples obtained in the first, second and third trimesters of gestation from women in the PIH and control groups. The concentration of copeptin in the second and third trimesters of pregnancy was statistically significantly higher in the PIH group (p< 0.05). For copeptin determined in the first trimester, which could be used to screen for PIH, the area under the ROC curve was 0.650. The highest risk of PIH occurred in patients with high concentrations of copeptin in the first trimester of pregnancy and obesity OR = 5.5 (95% CI 1.0-31.3). The risk of PIH was augmented in patients with high levels of copeptin and an abnormal Doppler result of the uterine arteries OR = 28.4 (95% CI 5.3-152). In conclusion, copeptin levels were found to be elevated in pregnant women before the diagnosis of PIH; however, copeptin should not be used as a stand-alone marker. The combination of copeptin concentration with the other risk factors (diabetes, maternal age and preeclampsia in previous pregnancy) did not improve the diagnostic values of the use of copeptin in the PIH risk assessment, but the combination of copeptin concentration with BMI may be useful in clinical practice. Measurement of copeptin together with a Doppler examination of uterine arteries in the first trimester of pregnancy may be a useful marker in predicting the development of PIH.

Copeptin:Copeptin is secreted in equimolar amount to Arginine Vasopressin (AVP) but can easily be measured with a sandwich immunoassay. Both peptides, copeptin and AVP, show a high correlation. Accordingly, copeptin mirrors the amount of AVP in the circulation and its measurement provides an attractive marker in the differential diagnosis of diabetes insipidus.The polyuria polydipsia syndrome:Diabetes insipidus-either central or nephrogenic-has to be differentiated from primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since many decades, the "gold standard" for differential diagnosis has been the classical water deprivation test, which has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 hours and is cumbersome for patients. Clinical signs and symptoms as well as MRI characteristics overlap between patients with diabetes insipidus and primary polydipsia. Direct measurement of AVP upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay.Copeptin as diagnostic tool in the polyuria polydipsia syndrome:We have recently shown that copeptin, without prior water deprivation, identifies patients with nephrogenic diabetes insipidus. On the other hand, for the more difficult differentiation between central diabetes insipidus and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these two entities with a high diagnostic accuracy, and is superior to the water deprivation test. It is important to note that close sodium monitoring during the hypertonic saline test is a prerequisite.Conclusion:Therefore, we propose that copeptin upon hypertonic saline infusion should become the new standard test in the differential diagnosis of diabetes insipidus.