Copeptin assays in children for the differential diagnosis of polyuria‐polydipsia syndrome and reference levels in hospitalized children

The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI). The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting. In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data. The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T < or =0.01 microg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%. The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).

Arginine vasopressin (AVP) is a key regulator of water balance, but its instability makes reliable measurement difficult and precludes routine use. We present a method for quantifying AVP release by use of copeptin, a glycopeptide comprising the C-terminal part of the AVP prohormone. We measured copeptin in 50-microL serum and plasma samples from healthy individuals and from critically ill patients with sepsis. Our sandwich immunoluminometric assay used 2 polyclonal antibodies to amino acids 132-164 of pre-provasopressin. The assay yielded results within 3 h. The analytical detection limit was 1.7 pmol/L, and the interlaboratory CV was 2.25 pmol/L. The assay was linear on dilution of the analyte. Ex vivo copeptin stability (<20% loss of analyte) for at least 7 days at room temperature and 14 days at 4 degrees C was shown for serum and EDTA-, heparin-, and citrate plasma. Copeptin (median, 4.2 pmol/L; range, 1-13.8 pmol/L) was detectable in 97.5% of 359 healthy individuals and was not associated with age. Median concentrations were considerably higher in men than women, increased significantly after exercise, and were influenced by fasting and water load. Copeptin was significantly (P <0.001) increased in 60 critically ill patients with sepsis (median, 79.5 pmol/L; range, 10.6-228.0 pmol/L). The correlation between copeptin and AVP for 110 samples was r = 0.78 (P <0.0001). Copeptin is stable for days after blood withdrawal and can be quickly and easily measured. The copeptin assay may be a useful alternative to direct measurement of AVP concentration.

Early prediction of outcome in patients with ischemic stroke is important. Vasopressin is a stress hormone. Its production rate is mirrored in circulating levels of copeptin, a fragment of provasopressin. We evaluated the prognostic value of copeptin in acute stroke patients. In a prospective observational study, copeptin was measured using a new sandwich immunoassay on admission in plasma of 362 consecutive patients with an acute ischemic stroke. The prognostic value of copeptin to predict the functional outcome (defined as a modified Rankin Scale score of or=3), mortality within 90 days, was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Patients with an unfavorable outcomes and nonsurvivors had significantly increased copeptin levels on admission (p <0.0001 and p <0.0001). Receiver operating characteristics to predict functional outcome and mortality demonstrated areas under the curve of copeptin of 0.73 (95% confidence interval [CI], 0.67-0.78) and 0.82 (95% CI, 0.76-0.89), which was comparable with the National Institutes of Health Stroke Scale score but superior to C-reactive protein and glucose (p <0.01). In multivariate logistic regression analysis, copeptin was an independent predictor of functional outcome and mortality, and improved the prognostic accuracy of the National Institutes of Health Stroke Scale to predict functional outcome (combined areas under the curve, 0.79; 95% CI, 0.74-0.84; p <0.01) and mortality (combined areas under the curve, 0.89; 95% CI, 0.84-0.94; p <0.01). Copeptin is a novel, independent prognostic marker improving currently used risk stratification of stroke patients. Ann Neurol 2009;66:799-808.