What are arginine vasopressin (AVP)/copeptin levels used for?

Arginine Vasopressin/Copeptin Levels: Diagnostic and Clinical Applications

Arginine vasopressin (AVP)/copeptin levels are primarily used for diagnosing disorders of water homeostasis, with copeptin serving as a stable and reliable surrogate marker for AVP that enables accurate assessment of vasopressin secretion in clinical practice. 1

What is AVP/Copeptin?

• Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is a key hormone regulating water balance, cardiovascular homeostasis, and endocrine stress response 2
• Copeptin is the C-terminal part of the AVP precursor peptide (pre-proAVP) and is released in an equimolar ratio with AVP from the neurohypophysis 1, 2
• Unlike AVP which is unstable in isolated plasma with a short half-life, copeptin remains stable for days after blood withdrawal (up to 7 days at room temperature and 14 days at 4°C), making it an ideal surrogate marker 1

Diagnostic Applications

Nephrogenic Diabetes Insipidus (NDI)

• In adults, baseline plasma copeptin levels above 21.4 pmol/L are diagnostic for nephrogenic diabetes insipidus (NDI), distinguishing it from other polyuric disorders 3
• Adults with plasma copeptin <21.4 pmol/L should undergo further testing for AVP deficiency (central diabetes insipidus) and primary polydipsia using infusion tests with hypertonic saline or arginine 3
• Genetic testing for AQP2, AVPR2, and AVP genes is recommended as the first-line diagnostic approach for suspected congenital NDI, with copeptin measurement serving as an alternative when genetic testing is unavailable or inconclusive 3

Differential Diagnosis of Polyuric Disorders

• Copeptin measurement helps differentiate between various causes of polyuria and hyponatremia 3:
  • Nephrogenic diabetes insipidus (elevated copeptin)
  • Central diabetes insipidus (low copeptin)
  • Primary polydipsia (normal or low copeptin)
• The differential diagnosis also includes poorly controlled diabetes mellitus, Bartter syndrome, distal renal tubular acidosis, and nephronophthisis 3

Cardiovascular and Critical Care Applications

• Copeptin serves as a diagnostic and prognostic biomarker in cardiovascular diseases, including:
  • Rapid rule-out of acute myocardial infarction
  • Mortality prediction in heart failure
  • Prognostic assessment in stroke 2
• In critically ill patients with sepsis, copeptin levels are significantly elevated (median 79.5 pmol/L vs. 4.2 pmol/L in healthy individuals) 1

Hyponatremia Management

• Copeptin measurement aids in diagnosing syndrome of inappropriate antidiuretic hormone secretion (SIADH), particularly in cancer patients with paraneoplastic SIADH 4
• Elevated copeptin levels in hyponatremic patients with cirrhosis help identify hypervolemic hyponatremia, guiding treatment decisions regarding vaptans (vasopressin receptor antagonists) 3

Clinical Considerations

• Normal copeptin levels in healthy individuals have a median of 4.2 pmol/L (range 1-13.8 pmol/L) 1
• Copeptin levels are influenced by:
  • Gender (higher in men)
  • Physical exercise (increases with exertion)
  • Fasting status and water load 1
• Copeptin measurement requires only 50 μL of serum or plasma and yields results within 3 hours 1

Therapeutic Implications

• Copeptin levels can guide treatment decisions for vasopressin receptor antagonists (vaptans) in hypervolemic hyponatremia 3
• In patients with liver cirrhosis, caution is needed when using vaptans as drug metabolism may be approximately 60% slower in uncompensated cirrhosis 3, 5
• Monitoring copeptin levels is important in patients undergoing pituitary surgery to detect changes in water metabolism and AVP regulation, which are common complications 3

Emerging Applications

• Copeptin shows promise as a prognostic marker in chronic kidney disease, with associations between high circulating copeptin and decline in glomerular filtration rate 6
• Research suggests copeptin may predict increased risk of complications such as myocardial infarction, heart failure, diabetes mellitus, and metabolic syndrome 6

In clinical practice, copeptin measurement offers a practical alternative to direct AVP measurement, providing valuable diagnostic information from a single plasma sample with greater stability and ease of measurement 1, 7.