Utility of copeptin in predicting non-pathological postoperative polyuria in patients affected by acromegaly undergoing pituitary neurosurgery.

PURPOSE: Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes in diuresis in individuals with acromegaly undergoing neurosurgery remains unexplored. Our study aimed to assess changes in postoperative fluid balance in acromegaly patients and correlate them with both copeptin and growth hormone (GH) levels. METHODS: This was a secondary analysis of a prospective study involving 15 acromegaly patients undergoing endoscopic endonasal resection at our University Hospital. Fluid balance was assessed daily, and copeptin and GH levels were evaluated preoperatively (T0), and serially on the morning of the first (T2) and second (T3) postoperative day, with an additional measurement of copeptin one hour post-extubation (T1). Patients with pre-existing or post-neurosurgical CDI were excluded from the analysis. RESULTS: Most patients (11/15) exhibited a negative fluid balance on the second postoperative day, with 4 developing polyuria. Postoperative GH levels did not differ significantly between polyuric and non-polyuric patients, but GH measured at T2 correlated significantly with negative total balance (r = -0.519, p = 0.048). Copeptin levels at T1 were significantly higher in those who developed polyuria (p = 0.013), and a copeptin value > 39.9 pmol/L at T1 showed excellent ability (Sensitivity 100%, Specificity 90.9%, p < 0.001) in predicting postoperative polyuria. Additionally, polyuric patients exhibited a higher T1 / T3 copeptin ratio (p = 0.013) and a negative fluid balance was associated with the remission of acromegaly at 12 months (p = 0.046). CONCLUSION: The early assessment of copeptin, in addition to facilitating the rapid identification of individuals at increased risk of developing CDI, could also allow the recognition of subjects with a tendency towards non-pathological polyuria in the postoperative setting, at least in individuals affected by acromegaly.

Effectiveness of Copeptin, MR-proADM and MR-proANP in Predicting Adverse Outcomes, Alone and in Combination with Traditional Severity Scores, a Secondary Analysis in COVID-19 Patients Requiring Intensive Care Admission.

Objective: To investigate whether copeptin, MR-proADM and MR-proANP, alone or integrated with the SOFA, MuLBSTA and SAPS II scores, are capable of early recognition of COVID-19 ICU patients at increased risk of adverse outcomes. Methods: For this predefined secondary analysis of a larger cohort previously described, all consecutive COVID-19 adult patients admitted between March and December 2020 to the ICU of a referral, university hospital in Northern Italy were screened, and clinical severity scores were calculated upon admission. A blood sample for copeptin, MR-proADM and MR-proANP was collected within 48 h (T1), on day 3 (T3) and 7 (T7). Outcomes considered were ICU and in-hospital mortality, bacterial superinfection, recourse to renal replacement therapy (RRT) or veno-venous extracorporeal membrane oxygenation, need for invasive mechanical ventilation (IMV) and pronation. Results: Sixty-eight patients were enrolled, and in-hospital mortality was 69.1%. ICU mortality was predicted by MR-proANP measured at T1 (HR 1.005, 95% CI 1.001-1.010, p = 0.049), although significance was lost if the analysis was adjusted for procalcitonin and steroid treatment (p = 0.056). Non-survivors showed higher MR-proADM levels than survivors at all time points, and an increase in the ratio between values at baseline and at T7 > 4.9% resulted in a more than four-fold greater risk of in-hospital mortality (HR 4.417, p < 0.001). Finally, when considering patients with any reduction in glomerular filtration, an early copeptin level > 23.4 pmol/L correlated with a more than five-fold higher risk of requiring RRT during hospitalization (HR 5.305, p = 0.044). Conclusion: Timely evaluation of MR-proADM, MR-proANP and copeptin, as well as changes in the former over time, might predict mortality and other adverse outcomes in ICU patients suffering from severe COVID-19.

C-Terminal Proarginine Vasopressin is Associated with Disease Outcome and Mortality, but not with Delayed Cerebral Ischemia in Critically Ill Patients with an Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is an important indication for intensive care unit admission and may lead to significant morbidity and mortality. We assessed the ability of C-terminal proarginine vasopressin (CT-proAVP) to predict disease outcome, mortality, and delayed cerebral ischemia (DCI) in critically ill patients with aSAH compared with the World Federation of Neurological Surgeons (WFNS) score and Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model. METHODS: C-terminal proarginine vasopressin was collected on admission in this single-center, prospective, observational cohort study. The primary aim was to investigate the relationship between CT-proAVP and poor functional outcome at 1 year (Glasgow Outcome Scale score 1-3) in a multivariable logistic regression model adjusted for WFNS and APACHE IV scores. Secondary aims were mortality and DCI. The multivariable logistic regression model for DCI was also adjusted for the modified Fisher scale. RESULTS: In 100 patients, the median CT-proAVP level was 24.9 pmol/L (interquartile range 11.5-53.8); 45 patients had a poor 1-year functional outcome, 19 patients died within 30 days, 25 patients died within 1 year, and DCI occurred in 28 patients. Receiver operating characteristics curves revealed high accuracy for CT-proAVP to identify patients with poor 1-year functional outcome (area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.77-0.92, p < 0.001), 30-day mortality (AUC 0.84, 95% CI 0.76-0.93, p < 0.001), and 1-year mortality (AUC 0.79, 95% CI 0.69-0.89, p < 0.001). CT-proAVP had a low AUC for identifying patients with DCI (AUC 0.67, 95% CI 0.55-0.79, p 0.008). CT-proAVP ≥ 24.9 pmo/L proved to be a significant predictor for poor 1-year functional outcome (odds ratio [OR] 8.04, 95% CI 2.97-21.75, p < 0.001), and CT-proAVP ≥ 29.1 pmol/L and ≥ 27.7 pmol/L were significant predictors for 30-day and 1-year mortality (OR 9.31, 95% CI 1.55-56.07, p 0.015 and OR 5.15, 95% CI 1.48-17.93, p 0.010) in multivariable models with WFNS and APACHE IV scores. CT-proAVP ≥ 29.5 pmol/L was not a significant predictor for DCI in a multivariable model adjusted for the modified Fisher scale (p = 0.061). CONCLUSIONS: C-terminal proarginine vasopressin was able to predict poor functional outcome and mortality in critically ill patients with aSAH. Its prognostic ability to predict DCI was low. TRIAL REGISTRATION: Nederlands Trial Register: NTR4118.

Higher plasma levels of CT-proAVP are linked to less anxiety in men but not women with cardiovascular risk factors: Results from the observational Diast-CHF study.

AIM: Using data from the multicenter, observational Diast-CHF (Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure) study, this post-hoc analysis aimed at assessing the association between serum concentrations of C-terminal pro-arginine vasopressin (CT-proAVP) and anxiety in patients with cardiovascular risk factors. BACKGROUND: Animal studies have demonstrated that centrally released AVP is involved in the development of anxiety-like behaviors, however, it is unknown whether, also in humans, CT-proAVP used as a proxy for the co-secreted AVP is associated with self-reported anxiety. METHODS: In 1463 study participants with cardiovascular risk factors (mean age 66.7 ± 8.1 years, 51.3% males, mean left ventricular ejection fraction 59.8 ± 8.3%), serum concentrations of CT-proAVP were measured by means of an ELISA assay, and anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Data showed that there was a significant and inverse correlation between HADS anxiety and CT-proAVP (rho = -0.074; p = 0.005). Serum CT-proAVP and the HADS anxiety differed between the two sexes: men displayed lower anxiety (4.7 ± 3.5 versus 5.5 ± 3.7) and had higher CT-proAVP levels (5.8 pmol/L, interquartile range 3.5-9.9 pmol/L versus 3.0 pmol/L, interquartile range 2.0-4.7) than women (both, p < 0.001). Using univariate ANOVA adjusted for age, body-mass index, estimated glomerular filtration rate, left ventricular ejection fraction, 6-minute walking distance, SF-36 physical functioning, and the natriuretic peptides NT-proBNP and MR-proANP, the interaction term sex*CT-proAVP was significantly associated with anxiety (p = 0.006). Further analysis showed that CT-proAVP was inversely related to anxiety only in men (B = -0.991; 95%CI = -1.650 to -0.331; p = 0.003), but not in women (p = 0.335). CONCLUSION: In male study participants with cardiovascular risk factors, serum concentrations of CT-proAVP showed an inverse association with anxiety, which was independent from the severity of physical impairment.

Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy.

BACKGROUND: Vasopressin and adrenomedullin and their stable by-products copeptin and midregional part of proadrenomedullin (MR-proADM) are promising biomarkers for the development of preeclampsia. However, clinical use is hampered by the lack of trimester-specific reference intervals. We therefore estimated reference intervals for copeptin and MR-proADM in disease-free Dutch women throughout pregnancy. METHODS: Apparently healthy low risk pregnant women were recruited. Exclusion criteria included current or past history of endocrine disease, multiple pregnancy, use of medication known to influence thyroid function and current pregnancy as a result of hormonal stimulation. Women who miscarried, developed hyperemesis gravidarum, hypertension, pre-eclampsia, hemolysis elevated liver enzymes and low platelets, diabetes or other disease, delivered prematurely or had a small for gestational age neonate were excluded from analyses. Blood samples were collected at 9-13 weeks (n=98), 27-29 weeks (n=94) and 36-39 weeks (n=91) of gestation and at 4-13 weeks post-partum (PP) (n=89). Sixty-two women had complete data during pregnancy and PP. All analyses were performed on a Kryptor compact plus. RESULTS: Copeptin increases during pregnancy, but 97.5th percentiles remain below the non-pregnant upper reference limit (URL) provided by the manufacturer. MR-proADM concentrations increase as well during pregnancy. In trimesters 2 and 3 the 97.5th percentiles are over three times the non-pregnant URL provided by the manufacturer. CONCLUSIONS: Trimester- and assay-specific reference intervals for copeptin and MR-proADM should be used. In addition, consecutive measurements and the time frame between measurements should be considered as the differences seen with or in advance of preeclampsia can be expected to be relatively small compared to the reference intervals.