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Potential Biomarker in Diagnosis and Prognosis of various Diseases

06 Apr 2023

The Need:
The new biomarkers have shown a good potential for important decision making in diagnosis as well as prognosis of various diseases in clinical practice.

Copeptin can be one of these biomarkers as compared to Arginine vasopressin (AVP). AVP is easily stimulated by exposure of the body to endogenous stress but measurement of AVP concentration becomes difficult because it is subject to pre-analytical and analytical errors, therefore not used in clinical practice. Whereas Copeptin is a part of precursor pre-provasopressin (pre-proAVP). Activation of AVP system stimulates Copeptin secretion into the circulation from the posterior pituitary gland in equimolar amounts with AVP and thus can be used as surrogate biomarker.

Advantages of Copeptin over AVP:

  • Copeptin has a longer half-life than vasopressin, hence it is easier to detect and directly reflect vasopressin release

  • Unlike AVP, Copeptin is stable in EDTA plasma for up to 14 days at room temperature, while in citrate and heparin plasma copeptin is stable for 7 days

  • Detection of Copeptin doesn't require extraction or other complex pre-analytical steps

  • It can easily be measured ex vivo by manual or fully automated chemiluminescence assays as a replacement biomarker for unstable AVP

  • The assay requires minimal serum or plasma volume and the overall time for completing the analysis is between 20 and 30 minutes

  • Copeptin is suitable for routine measurements as an alternative to AVP

Copeptin as a Diagnostic and Prognostic marker
In stressful situations such as illness, the relationship between plasma osmolality and AVP is lost because AVP with corticotropin-releasing hormone (CRH) leads to the production of adrenocorticotropic hormone (ACTH) and cortisol
Serum cortisol is proportional to stress levels, predicting prognostic outcome in different diseases. However, cortisol is influenced by strong circadian rhythm and its measurement as a free hormone places copeptin as a more reliable hormone for determination of stress levels.

Use of Copeptin as a Diagnostic and Prognostic Marker in Various Diseases:

  • Acute Myocardial Infarction

  • Heart Failure

  • Chronic obstructive pulmonary disease

  • lower respiratory tract infections

  • Acute dyspnea

  • Sepsis

  • Hemorrhagic and septic shock

  • Diabetes mellitus

  • Autosomal dominant polycystic kidney disease (ADPKD)

  • Ischemic stroke and traumatic brain injury

  • Hyponatremia

Combined measurements of plasma Copeptin and Troponin-I levels for early exclusion of acute myocardial infarction

  • Combined measurements of troponin and copeptin aided in early and safe rule-out of acute MI This combination can improve the diagnostic performance in patients especially in the emergency department (ED)

  • Copeptin, and thereby vasopressin, are released by endogenous stress and increase immediately after the onset of chest pain. The combination of an endogenous stress marker and a marker of cell necrosis can improve the diagnostic performance in patients with chest pain at the time of presentation in the emergency department

Copeptin, and thereby vasopressin, are released by endogenous stress and increase immediately after the onset of chest pain. The combination of an endogenous stress marker and a marker of cell necrosis can improve the diagnostic performance in patients with chest pain at the time of presentation in the emergency department

  • Copeptin, and thereby vasopressin, are released by endogenous stress and increase immediately after the onset of chest pain. The combination of an endogenous stress marker and a marker of cell necrosis can improve the diagnostic performance in patients with chest pain at the time of presentation in the emergency department

  • The combination of Copeptin and cTn has been proposed to be used for the assessment of patients with suspected AMI. Although Copeptin is nonspecific to myocardial injury, it responds to an immediate neural trigger with concentrations rising early and decreasing gradually over several hours

Comparison of the Temporal release pattern of Copeptin with Conventional Biomarkers in acute myocardial infarction (AMI)

  • Copeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day

  • Addition of Copeptin to cardiac troponin T (cTnT) improved the diagnostic accuracy of a measurement on admission in patients presenting with chest pain within 3 h after symptom onset. However, although Copeptin levels are elevated much earlier than CK-MB or cTnT and drop in the 6 h thereafter in patients with AMI, a comparison of temporal release patterns after the onset of AMI between Copeptin and conventional cardiac biomarkers has not been made for more than 6 h, when levels were still elevated.

Conclusion

  • Copeptin, could be a potentially promising biomarker in diagnosis of various diseases and prediction of functional outcomes. It releases into the circulation under endogenous stress, even mild to moderate stress situations contribute to release of Copeptin. These reasons have led to a handful of research on Copeptin in various diseases.

  • Since it is not specific to a certain disease, Copeptin could be used as an adjunct with more specific biomarkers where it may increase diagnostic accuracy and aid clinicians in making better diagnostic judgements. However, Copeptin is still in its infancy and more research is needed in order to prove its clinical usefulness.

Conclusion

  1. Ahmed WO, Elmaadawy A, Yehia A, Elmaraghi S. Combined measurements of plasma copeptin and troponin-I levels for early exclusion of acute myocardial infarction. The Egyptian Journal of Critical Care Medicine. 2016 Dec 1;4(3):127-32

  2. Shin H, Jang BH, Lim TH, Lee J, Kim W, Cho Y, Ahn C, Choi KS. Diagnostic accuracy of adding copeptin to cardiac troponin for non-ST-elevation myocardial infarction: A systematic review and meta-analysis. PloS one. 2018 Jul 6;13(7):e0200379

  3. Gu YL, Voors AA, Zijlstra F, Hillege HL, Struck J, Masson S, Vago T, Anker SD, Van Den Heuvel AF, Van Veldhuisen DJ, De Smet BJ. Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction. Clinical research in cardiology. 2011 Dec;100(12):1069-76.

  4. Doba L, Cullen Edozien K. Copeptin and its potential role in diagnosis and prognosis of various diseases. Biochemia medica. 2013 Jun 15;23(2):172-90.





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