Copeptin Concentrations Research Articles

Combined Arginine and Insulin Stimulation Elicits a Robust and Consistent Copeptin Response in Short Children

Introduction: Copeptin, co-secreted with arginine vasopressin, is regulated by osmotic and volume stimuli but also responds to intravenous arginine and insulin-induced hypoglycemia. The serum copeptin response to the latter agents has been studied in adults but only to a limited extent in children. The objective of this study was to describe the copeptin response to combined arginine and insulin in children with normal posterior pituitary function. Methods: We conducted a prospective, single-arm assessment of serum copeptin concentrations in children (age 7–16 years, n = 38) undergoing growth hormone stimulation testing with an arginine-insulin tolerance test (AITT) for short stature or growth deceleration in a tertiary referral center. After overnight fasting, arginine (500 mg/kg) was administered between 0 and 30 min intravenously (IV) followed by insulin (0.1 units/kg IV) at 60 min. Copeptin serum concentrations were measured at baseline (0 min), at the post-arginine peak (60 min), and at the post-insulin peak (90 min; 30 min post-insulin), respectively. The main outcome was the peak copeptin concentration. Results: Mean ± SD copeptin concentrations increased from 9.9 ± 5.0 pmol/L at 0 min to 13.2 ± 5.8 pmol/L at 60 min (p < 0.0001 vs. 0 min) and 27.7 ± 14.2 pmol/L at 90 min (p < 0.0001 vs. 0 and 60 min). There was no significant correlation between copeptin concentrations and age, BMI, pubertal status, cortisol, growth hormone, or glucose concentrations. Discussion/Conclusion: Arginine and insulin appear to have an additive and consistent effect resulting in significant stimulation of copeptin secretion in children. The AITT may be a useful tool to evaluate for normal posterior pituitary function in this age-group, with potential implications for the evaluation of polyuria-polydipsia syndrome.

Copeptin: A potential marker for the prediction of poor ovarian reserve in the ınfertile women.

There is actually no evidence regarding the physiological effects of copeptin in infertile women with different ovarian reserve types. This study aimed to investigate the relationship of serum copeptin level with poor ovarian reserve (POR) and to reveal the predictive value of copeptin for POR development in the infertile women. All participant women were classified as the control group (n=77) included the women with diagnosis of unexplained infertility and the POR group (n=61) was composed of the women who met the European Society of Human Reproduction and Embryology consensus on POR [serum anti-Müllerian hormone (AMH) concentrations below 1.1 ng/mL]. The biochemical tests, including estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone, AMH and copeptin were analysed. The analyses of serum copeptin concentrations were measured by the means of competitive enzyme immunoassay. A significant increase in the serum copeptin level existed only in the POR group. There was a significant positive correlation between serum copeptin with E2 and FSH levels in the POR group. Significant negative correlations between copeptin and AMH concentrations (r=-0.310, p=0.015) and between copeptin concentration and antral follicle counts (r=-0.284, p=0.027) were detected only in the POR group. The estimated areas under receiver operating characteristic curves for serum concentration were found to be statistically significant with a cut-off value of 3.52 (95% confidence interval 0.519-0.709), sensitivity 0.90 and specificity 0.72. This study confirmed that there was an elevated serum copeptin concentration in the infertile women with POR and that serum copeptin concentration may have a predictive value for POR diagnosis.

Limited Role of Endogenous Vasopressin/Copeptin in Stimulation of ACTH-Cortisol Secretion during Glucagon Stimulation Test in Humans.

Copeptin is a stable part of a vasopressin precursor that closely mirrors arginine vasopressin (AVP) secretion. It is known that AVP/copeptin is also released in response to nonosmotic stimuli, such as stress evoked during anterior pituitary dynamic testing. In order to examine the role of AVP in challenging the hypothalamo-pituitary-adrenal axis, we assessed adrenocorticotropic hormone (ACTH), cortisol, copeptin and growth hormone (GH) during a glucagon stimulation test (GST) in 10 patients with satisfactory initial cortisol concentrations (mean ± SD: 20.34 ± 5.10 µg/dL) and failure to show any further cortisol increment on stimulation. For comparison, we measured copeptin in two subjects during an insulin tolerance test (ITT). During GST, there was an increase in copeptin (p = 0.02, average individual increase of 98%, range 10% to 321%). There was a robust increase in GH (p = 0.002, average increase 3300%), a decline in cortisol (p = 0.02, average decline 21.8%) and a fall in ACTH (p = 0.06). The relative increase in copeptin during ITT (176% and 52.2%) overlapped with increments observed during GST; however, here there was an increase in cortisol (20.45→24.26 µg/dL and 4.23→29.29 µg/dL, respectively). There was a moderate correlation between copeptin and GH concentrations (r = 0.4235, p = 0.0007). These results confirm that AVP is not crucial for ACTH-cortisol stimulation, though it might be an important factor in GH secretion.

PMON180 Extremely Elevated Serum Copeptin Concentrations Following Venipuncture Occur in Approximately 5% of Children and May Affect Proper Interpretation of Copeptin Measurement

Abstract Introduction The secretion of copeptin, an easily measurable surrogate of arginine vasopressin (AVP), is mainly regulated by osmotic and volume stimuli, but also increases in situations of physical stress. Venipuncture has been found to be a stressful procedure, due to physical pain and anxiety, particularly in children. Falsely elevated copeptin concentrations can substantially affect establishment of reference intervals and interpretation of results in conditions such as syndrome of inappropriate antidiuresis, sepsis, infections. We thus tested the hypothesis that venipuncture, as a stressful stimulus, could stimulate copeptin secretion in children. Subjects &amp; Methods We evaluated 92 children (75% males, 5-19 years) enrolled in a study assessing fasting and stimulated serum copeptin concentrations in response to arginine-hydrochloride (500 mg/kg IV in 30 minutes, ArgST) or insulin (0.1 U/Kg IV, insulin tolerance test/ITT) during GH stimulation tests in healthy short children. Subjects underwent phlebotomy for placement of an IV cannula (angiocath) by trained nurses, without percutaneous anesthesia. Copeptin was measured at 0 min. and at sampling times of the expected copeptin peak (60 min post arginine; 45, 60 min post-insulin) by the immunometric B.R.A.H.M.S. Kryptor assay (Quest laboratories) Results Two distinct groups of fasting copeptin values were identified. The majority of subjects, 86/92 (93.5%, "controls") had serum copeptin concentrations in the expected range for overnight fasting (median 9, IQR 6-12, range 2-29 pM/L). Six subjects (6.5%) were outliers with very elevated copeptin values (&amp;gt;50 in one, &amp;gt;100 pM/L in five of them). In 50 controls who underwent ArgST, copeptin increased from a median of 9 (IQR 6-13, range 2-25) to 11 (IQR 8-15, range 2-28) pM/L at 60 min; In the 5 outliers who underwent ArgST, it paradoxically decreased, but remained elevated, from 272 (IQR 154-406, range 62-1361) to 95.5 (IQR58-128, range 42-282) pM/L at 60 min. Similarly, in 8 controls who underwent ITT, copeptin increased minimally from a median of 8 (IQR 7-11, range 5-12) to 10 (IQR10-14, range 6-17) at 45 min, and 9(IQR 2-13, range 8-12) pM/L at 60 min. In the outlier who underwent ITT, copeptin decreased from 202 (0 min) to 63 (45 min) and 51(60 min) pM/L. None of these children had abnormalities of fluid regulation (polydipsia, polyuria, abnormal serum Na+ levels). The highest copeptin level (&amp;gt;1000 pM/L) occurred in a subject who had 3 successive attempts at phlebotomy. Conclusions Very elevated serum concentrations of copeptin occur in a minority of pediatric subjects undergoing phlebotomy, suggesting that pain of venipuncture can be a potent stimulus of copeptin secretion. Unexplained high values were observed in another pediatric study (Bonnet, Clin Endocrinol 2022;96: 47-53). This information is relevant to clinicians measuring copeptin for diagnostic or prognostic purposes or to establish reference values. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Role of copeptin in diagnosis and outcome prediction in patients with heart failure: a systematic review and meta-analysis

ABSTRACT Background/Context Heart failure (HF) is a heterogeneous condition characterized by increased morbidity and mortality. Objective This systematic review and meta-analysis of 19 studies was conducted to evaluate the role of copeptin in diagnosis and outcome prediction in HF patients. Materials and methods A systematic literature search for clinical trials reporting copeptin levels in HF patients was performed using EMBASE, PubMed, Cochrane Register of Controlled Trials, and Google Scholar. Articles from databases published by 2 January 2022, that met the selection criteria were retrieved and reviewed. The random effects model was used for analyses. Results Pooled analysis found higher mean copeptin levels in HF vs. non-HF populations (43.6 ± 46.4 vs. 21.4 ± 21.4; MD= 20.48; 95% CI: 9.22 to 31.74; p < 0.001). Pooled analysis of copeptin concentrations stratified by ejection fraction showed higher concentrations in HFrEF vs. HFpEF (17.4 ± 7.1 vs. 10.1 ± 5.5; MD= −4.69; 95% CI: −7.58 to −1.81; p = 0.001). Copeptin level was higher in patients with mortality/acute HF-related hospitalization vs. stable patients (31.3 ± 23.7 vs. 20.4 ± 12.8; MD= −13.06; 95% CI: −25.28 to −0.84; p = 0.04). Higher copeptin concentrations were associated with mortality and observed in all follow-up periods (p < 0.05). Conclusions The present meta-analysis showed that elevated copeptin plasma concentrations observed in HF patients are associated with an increased risk of all-cause mortality, thus copeptin may serve as predictor of outcome in HF.

Clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients

Background: Copeptin is the carboxyl-terminal part of the vasopressin precursor protein, and its concentration is an independent predictor of the onset of chronic kidney disease and a rapid decline in the glomerular filtration rate. The glomerular filtration rate is regarded as the best indicator of kidney transplant function and is a predictor of graft and patient survival. We investigated the clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients.Methods: We measured serum creatinine, cystatin C, and copeptin concentrations in renal transplant recipients on the day of their operation, as well as on postoperative days 3, 7, 30, and 365. Acute rejection was defined as a sudden decrease in renal function accompanied by histological changes.Results: Eight renal transplant recipients were enrolled in the study from July 2018 to December 2019. Four patients experienced histologically confirmed transplant rejection. All four cases involved acute T-cell rejection. No significant correlation was found between the copeptin level and the presence or absence of rejection at any time point. In subgroup analyses, changes in creatinine, the estimated glomerular filtration rate, cystatin, and copeptin did not show statistical significance.Conclusions: We anticipated that copeptin would be useful to identify individuals at high risk of transplant rejection; however, our study failed to show an association. Further research will be needed to overcome the limitations of this study.

Nitric oxide metabolites: associations with cardiovascular biomarkers and clinical parameters in patients with HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is one of the most rapidly growing cardiovascular health burden worldwide, but there is still a lack of understanding about the HFpEF pathophysiology. The nitric oxide (NO) signalling pathway has been identified as a potential key element. The aim of our study was to investigate markers of NO metabolism [l-arginine (l-Arg), homoarginine (hArg), and asymmetric and symmetric dimethylarginine (ADMA and SDMA)], additional biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), mid-regional pro-adrenomedullin (MR-proADM), copeptin, and high-sensitivity C-reactive protein (hsCRP)], and the endothelial function in an integrated approach focusing on associations with clinical characteristics in patients with HFpEF. Seventy-three patients, prospectively enrolled in the 'German HFpEF Registry', were analysed. Inclusion criteria were left ventricular ejection fraction (LVEF)≥50%; New York Heart Association functional class≥II; elevated levels of NT-proBNP>125pg/mL; and at least one additional criterion for structural heart disease or diastolic dysfunction. All patients underwent transthoracic echocardiography, cardiopulmonary exercise testing, and pulse amplitude tonometry (EndoPAT™). Patients were categorized in two groups based on their retrospectively calculated HFA-PEFF score. Serum concentrations of l-Arg, hArg, ADMA, SDMA, NT-proBNP, ET-1, MR-proADM, copeptin, and hsCRP were determined. Patients had a median age of 74years, 47% were female, and median LVEF was 57%. Fifty-two patients (71%) had an HFA-PEFF score≥5 (definitive HFpEF), and 21 patients (29%) a score of 3 to 4 (risk for HFpEF). Overall biomarker concentrations were 126±32μmol/L for l-Arg, 1.67±0.55μmol/L for hArg, 0.74 (0.60;0.85) μmol/L for SDMA, and 0.61±0.10μmol/L for ADMA. The median reactive hyperaemia index (RHI) was 1.55 (1.38;1.87). SDMA correlated with NT-proBNP (r=0.291; P=0.013), ET-1 (r=0.233; P=0.047), and copeptin (r=0.381; P=0.001). ADMA correlated with ET-1 (r=0.250; P=0.033) and hsCRP (r=0.303; P=0.009). SDMA was associated with the left atrial volume index (β=0.332; P=0.004), also after adjustment for age, sex, and comorbidities. Biomarkers were non-associated with the RHI. A principal component analysis revealed two contrary clusters of biomarkers. Our findings suggest an impaired NO metabolism as one possible key pathogenic determinant in at least a subgroup of patients with HFpEF. We argue for further evaluation of NO-based therapies. Upcoming studies should clarify whether subgroups of HFpEF patients can take more benefit from therapies that are targeting NO metabolism and pathway.

Signs of Anxiety and Salivary Copeptin Levels in Dogs Diagnosed with Separation-Related Problems in a Short Separation Test

Simple SummaryUp to 56% of the general dog population show signs of separation-related problems, a group of problems characterized by highly variable phenotypes on which research, to date, has mostly provided contradictory findings. In the present study, we analyzed the behavior and salivary concentrations of copeptin, a biologically stable biomarker of stress, in dogs with separation distress and in dogs with no problems. The animals were tested before, during and after three-minute separation from the owner, in a new environment. Dogs in the two groups differed significantly in their activity levels and stress-relief activities during the three observation phases. In addition, a different tendency in the two groups was found in salivary copeptin concentration behavior.The need for faster diagnosis and more accurate treatment decisions in separation-related problems (SRPs) in dogs is urgent, and a more precise behavioral phenotyping and the development of biomarkers may be of great value. Vasopressin could be a potential non-invasive biomarker of anxiety in dogs with SRPs, but reliable measurement of its concentration is challenging. Here, we compared the behavior and salivary concentrations of copeptin, an arginine vasopressin surrogate, in dogs with SRPs (Case group, n = 13) and with no problems (Control group, n = 15) as they were introduced to a novel environment and subjected to a short episode of separation and reunion with the owner. Dogs in the Case group had greater odds of showing locomotory or oral behaviors during the pre- and post-separation than Controls, while the odds were significantly lower during separation. They also had greater odds of being persistent in seeking attention and proximity from the stranger during reunion. Overall, dogs with SRPs were more likely to express an anxiety-like state during the entire test than Controls, with separation from the owner, and even its anticipation, possibly accounting for this group difference. Although salivary copeptin concentrations did not differ between the two groups, a different trend was detected in Cases and Controls that is worth exploring in further validation studies involving a larger sample.

Vasopressin marker copeptin and the development of renal and metabolic disorders in patients with type 2 diabetes

Abstract. The aim of the study was to evaluate the possibility of using copeptin as a marker of renal and metabolic dysfunction in patients with type 2 diabetes.&#x0D; Methods: In this cross-sectional, observational study included 78 patients with type 2 diabetes mellitus complicated by diabetic nephropathy (DN) were examined. Patients were divided into 4 groups according to the stage of chronic kidney disease. Control group - 15 healthy subjects. Serum levels of copeptin and insulin were determined by enzyme-linked immunosorbent assay.&#x0D; Results: our studies have shown that the development of DN in type 2 diabetes is accompanied by a significant increase of copeptin concentration in blood plasma compared with controls and with diabetic patients without signs of nephropathy. The highest values of copeptin were found in the later stages of DN - in patients with albuminuria and impaired kidney filtration function. In patients with type 2 diabetes, a significant direct correlation was found between copeptin level and serum creatinine (r = 0.247, p &lt;0.03). We found more significant violations of glucose metabolism in DN patients with high serum levels of copeptin compared with patients with normal values of this factor. In particular, an increase in serum copeptin was accompanied by a significant increase in the HOMA index and insulin concentration.&#x0D; Conclusions. Our data indicate that the copeptin level reflects the functional state of the kidneys and can be considered a diagnostic marker of renal and cardiovascular lesions in type 2 diabetes.

Copeptin Release in Arterial Hypotension and Its Association with Severity of Disease in Critically Ill Children.

Low copeptin levels may indicate inadequate arginine-vasopressin release promoting arterial hypotension, whereas high copeptin concentrations may reflect disease severity. This single-center prospective non-randomized clinical trial analyzed the course of blood copeptin in critically ill normo- and hypotensive children and its association with disease severity. In 164 patients (median age 0.5 years (interquartile range 0.1, 2.9)), the mean copeptin concentration at baseline was 43.5 pmol/L. Though not significantly different after 61 h (primary outcome, mean individual change: −12%, p = 0.36, paired t-test), we detected 1.47-fold higher copeptin concentrations during arterial hypotension when compared to normotension (mixed-effect ANOVA, p = 0.01). In total, 8 out of 34 patients (23.5%) with low copeptin concentrations <10 pmol/L were hypotensive. Copeptin was highest in the adjusted mixed-effect regression analysis within the first day (+20% at 14 h) and decreased significantly at 108 h (−27%) compared to baseline (p = 0.002). Moreover, we found a significant association with vasopressor-inotrope treatment intensity, infancy (1–12 months) and cardiopulmonary bypass (all p ≤ 0.001). In conclusion, high copeptin values were associated with arterial hypotension and severity of disease in critically ill children. This study does not support the hypothesis that low copeptin values might be indicative of arginine-vasopressin deficiency.

Arginine Vasopressin is not elevated in Early Pregnancy Loss

BackgroundAdministration of arginine vasopressin (AVP) has been previously shown to influence myometrial contractility during the first trimester of pregnancy in women who were undergoing a planned therapeutic abortion. Consequently, it was hypothesized that AVP may play a role in early spontaneous pregnancy loss. AVP is made in a 1:1 molar ratio with copeptin; thus, copeptin can be used as a surrogate measure of AVP. While early pregnancy loss is likely a multifactorial problem, we sought to fill the gap in knowledge of the causes of using pre‐collected samples from pregnancies that subsequently underwent spontaneous abortion and matched controls.MethodsA retrospective case control study was performed using plasma samples from the Maternal Fetal Tissue Bank (IRB# 200910784) at the University of Iowa Hospitals &amp; Clinics. Whole blood samples were collected (ACD‐A tubes, Becton Dickinson) at confirmation of pregnancy appointments in which a viable pregnancy was detected by ultrasound (6‐10 weeks gestation). Samples were processed and plasma aliquots were snap frozen and stored at ‐80oC until analysis. Control samples (N=67) from viable, healthy pregnancies were matched by gestational age, race, ethnicity, and body mass index to cases (N=123). Copeptin was measured by an automated immunoassay (Brahms KRYPTOR) and total protein concentration via a bicinchoninic acid (BCA) protein assay (Pierce). Copeptin concentrations were normalized to total protein in samples. Continuous variables were analyzed by T test.ResultsNo significant differences were detected in plasma samples that were collected while the pregnancies appeared viable. Copeptin was 7.2 +/‐ 6.0 mg/dL in case plasma samples and 6.0 +/‐ 3.4 mg/dL in control plasma samples (P=0.066). It is unclear if vasopressin increases acutely prior to the occurrence of spontaneous abortion.ConclusionThese results suggest that vasopressin cannot be used to identify pregnancies at risk of early loss at the time of pregnancy confirmation.

Elevated Urinary Arginine Vasopressin Concentrations during Preeclamptic Pregnancies do not Persist Postpartum

BackgroundPreeclampsia (PreE) is a common hypertensive disorder during the second and third trimesters of pregnancy. It is estimated to affect 5‐7% of all U.S. pregnancies; about 400,000 pregnancies per year. PreE leads to increased risks of fetal abnormalities, pregnancy complications, chronic hypertension, and cardiovascular disease. Arginine vasopressin (AVP) plays an important role in controlling osmotic balance, regulating blood pressure, maintaining sodium homeostasis, and functioning of the kidney. AVP is secreted by the hypothalamus as a proprotein with copeptin. Because copeptin and vasopressin are secreted in a 1:1 molar ratio, copeptin measurements can be used a surrogate measure of vasopressin. Our lab has previously demonstrated that vasopressin, as measured by copeptin, is elevated in plasma and urine throughout preeclamptic pregnancies; even before PreE can be clinically diagnosed. However, it is unknown whether urine vasopressin is elevated chronically postpartum. Our objective was to determine whether there is a difference in copeptin concentration between women with and without a history of preeclampsia at 1‐4 years postpartum. We hypothesized that AVP concentrations of subjects who had received a PreE diagnosis would continue to be elevated postpartum.MethodsInclusion criteria for this study (IRB# 201808705) included being 1‐4 years postpartum, not currently pregnant, non‐prisoner, and able to provide informed consent. Women without (N=26; Age 34 +/‐ 3.4 yrs, BMI 25.99 +/‐ 6.34 kg/m2) and with a history (N=25; age 33 +/‐ 4.5 yrs, BMI 30.32 +/‐ 9.12 kg/m2) of preeclampsia in their most recent pregnancy were enrolled. Women fasted, did not smoke, and did not have caffeine for 4 hours prior to their study visit, nor did they have alcohol or exercise for the prior 24 hours. Urine samples were assayed for copeptin concentrations via an automated immunoassay (Brahms KRYPTOR), creatinine concentrations via a QuantiChrom assay, total protein concentrations via a bicinchoninic acid (BCA) protein assay, osmolality by freezing point depression, and specific gravity using a hydrometer.ResultsThere were no differences between the cohorts in race or ethnicity. There was no statistically significant difference in urinary copeptin, as a marker of AVP, in the postpartum period between women with vs. without a history of preeclampsia (4.5 vs. 3.2 mg/dL, P=0.4). No significant differences in copeptin were detected in women without a current hypertension diagnosis (5.49 mg/dL, N=43) and those being treated for hypertension (4.79 mg/dL, N=7, P=0.35).ConclusionsThis study suggests that copeptin, a surrogate measure for AVP, is not chronically elevated in urine after a preeclamptic pregnancy.

Response to a Water Bolus in Long Term Oral Contraceptive Users.

The purpose of our study was to determine the responses to an acute water bolus in long-term oral contraception (OCP) users. Seventeen female volunteers (27 ± 5 y, 64.1 ± 13.7 kg, 39.6 ± 5.9 kg/LBM) provided consent and enrolled in our study. All were long-term OCP users and participated in two trials, one during the active pill (High Hormone, HH) dose of their prescribed OCP and one during the sham pill (Low Hormone, LH) dose. Participants reported to the laboratory euhydrated, were fed breakfast, remained seated for 60 min and were provided a bolus of room temperature water in the amount of 12 mL/kg/LBM. Urine output over 180 min was measured. Nude body mass was measured pre- and post-trial. Urine specific gravity (USG) and urine osmolality were analyzed. Between trials, there were no differences in 3-h total urine volume (P = 0.296), 3-h USG (P = 0.225), 3-h urine osmolality (P = 0.088), or 3-h urine frequency (P = 0.367). Heart rate was not different between trials (P = 0.792) nor over time (P = 0.731). Mean arterial pressure was not different between trials (P = 0.099) nor over time (P = 0.262). Perceived thirst demonstrated a significant main effect for increasing over time regardless of trial (P < 0.001) but there was no difference between trials (P = 0.731). The urgency to void was not different between trials (P = 0.149) nor over time (P = 0.615). Plasma volume change was not different between trials (P = 0.847) (HH: −3.4 ± 5.0, LH post: −3.8 ± 4.5%) and plasma osmolality did not differ between trials (P = 0.290) nor over time (P = 0.967) (HH pre: 290 ± 4, HH post: 289 ± 4, LH pre: 291 ± 4, LH post: 291 ± 4 mosm/L). Blood glucose significantly decreased over time (P < 0.001) but there was no difference between trials (P = 0.780) (HH pre: 95.9 ± 113.9, HH post: 86.8 ± 6.5, LH pre: 95.9 ± 13.5, LH post: 84.6 ± 9.4 mmol/L). Copeptin concentration did not differ between phases of OCP use (P = 0.645) nor from pre- to post-trial (P = 0.787) Despite fluctuations in hormone concentrations, responses to a water bolus seem to be unaffected in OCP users in euhydrated, resting conditions.

Seasonal variation of vasopressin and its relevance for the winter peak of cardiometabolic disease: A pooled analysis of five cohorts.

BackgroundVasopressin concentration is typically higher at night, during stress, and in males, but readily lowered by water intake. Vasopressin is also a causal candidate for cardiometabolic disease, which shows seasonal variation.ObjectiveTo study whether vasopressin concentration varies by season in a temperate climate.MethodsThe vasopressin surrogate marker copeptin was analyzed in fasting plasma samples from five population-based cohorts in Malmö, Sweden (n = 25,907, 50.4% women, age 18−86 years). We investigated seasonal variation of copeptin concentration and adjusted for confounders in sinusoidal models.ResultsThe predicted median copeptin level was 5.81 pmol/L (7.18 pmol/L for men and 4.44 pmol/L for women). Copeptin exhibited a distinct seasonal pattern with a peak in winter (mid-February to mid-March) and nadir in late summer (mid-August to mid-September). The adjusted absolute seasonal variation in median copeptin was 0.62 pmol/L (95% confidence interval [CI] 0.50; 0.74, 0.98 pmol/L [95% CI 0.73; 1.23] for men and 0.46 pmol/L [95% CI 0.33; 0.59] for women). The adjusted relative seasonal variation in mean log copeptin z-score was 0.20 (95% CI 0.17; 0.24, 0.18 [95% CI 0.14; 0.23] in men and 0.24 [95% CI 0.19; 0.29] in women). The observed seasonal variation of copeptin corresponded to a risk increase of 4% for incident diabetes mellitus and 2% for incident coronary artery disease.ConclusionThe seasonal variation of the vaso-pressin marker copeptin corresponds to increased disease risk and mirrors the known variation in cardiometabolic status across the year. Moderately increased water intake might mitigate the winter peak of cardiometabolic disease.

Perioperative Supplemental Oxygen and Postoperative Copeptin Concentrations in Cardiac-Risk Patients Undergoing Major Abdominal Surgery-A Secondary Analysis of a Randomized Clinical Trial.

Noncardiac surgery is associated with hemodynamic perturbations, fluid shifts and hypoxic events, causing stress responses. Copeptin is used to assess endogenous stress and predict myocardial injury. Myocardial injury is common after noncardiac surgery, and is often caused by myocardial oxygen demand-and-supply mismatch. In this secondary analysis, we included 173 patients at risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients were randomly assigned to receive 80% or 30% oxygen throughout surgery and the first two postoperative hours. We evaluated the effect of supplemental oxygen on postoperative Copeptin concentrations. Copeptin concentrations were measured preoperatively, within two hours after surgery, on the first and third postoperative days. In total, 85 patients received 0.8 FiO2, and 88 patients received 0.3 FiO2. There was no significant difference in postoperative Copeptin concentrations between both study groups (p = 0.446). Copeptin increased significantly within two hours after surgery, compared with baseline in the overall study population (estimated effect: −241.7 pmol·L−1; 95% CI −264.4, −219.1; p < 0.001). Supplemental oxygen did not significantly attenuate postoperative Copeptin release. Copeptin concentrations showed a more immediate postoperative increase compared with previously established biomarkers. Nevertheless, Copeptin concentrations did not surpass Troponin T in early determination of patients at risk for developing myocardial injury after noncardiac surgery.

Copeptin Concentrations in Plasma of Healthy Neonates in Relation to Water-Electrolyte Homeostasis in the Early Adaptation Period.

Copeptin (CTproAVP) is a stable by-product of arginine–vasopressin synthesis and reflects its secretion by the pituitary gland, considered as a potential new marker of dehydration. The objective of the study was to investigate CTproAVP measured after the first 48 h of postnatal life in relation to serum effective osmolality, urine osmolality, and vessels filling according to the following variables: delivery mode, postnatal weight loss, fluids administered intravenously to the mother, and fluids given orally to the neonate. A prospective observational study was conducted with 200 healthy term infants (53% male) enrolled. Serum CTproAVP concentrations were measured using the ELISA kit; haematocrit, urine osmolality, serum effective osmolality were assessed after 48 h of life. Sonographic measurements of inferior vena cava (IVC) and aorta (Ao) were performed and IVC/Ao ratios were calculated. No correlations were found between CTproAVP concentrations and both serum effective osmolality and urine osmolality. There was also no association between CTproAVP concentrations and vessel filling represented by IVC/Ao index at 48 h of life.

The kinetic profiles of copeptin and mid regional proadrenomedullin (MR-proADM) in pediatric lower respiratory tract infections.

Kinetics of copeptin and mid regional proadrenomedullin (MR-proADM) during febrile pediatric lower respiratory tract infections (LRTI) are unknown. We aimed to analyze kinetic profiles of copeptin and MR-proADM and the impact of clinical and laboratory factors on those biomarkers. This is a retrospective post-hoc analysis of a randomized controlled trial, evaluating procalcitonin guidance for antibiotic treatment of LRTI (ProPAED-study). In 175 pediatric patients presenting to the emergency department plasma copeptin and MR-proADM concentrations were determined on day 1, 3, and 5. Their association with clinical characteristics and other inflammatory biomarkers were tested by non-linear mixed effect modelling. Median copeptin and MR-proADM values were elevated on day 1 and decreased during on day 3 and 5 (-26%; -34%, respectively). The initial concentrations of MR-proADM at inclusion were higher in patients receiving antibiotics intravenously compared to oral administration (difference 0.62 pmol/L, 95%CI 0.44;1.42, p<0.001). Intensive care unit (ICU) admission was associated with a daily increase of MR-proADM (increase/day 1.03 pmol/L, 95%CI 0.43;1.50, p<0.001). Positive blood culture in patients with antibiotic treatment and negative results on nasopharyngeal aspirates, or negative blood culture were associated with a decreasing MR-proADM (decrease/day -0.85 pmol/L, 95%CI -0.45;-1.44), p<0.001). Elevated MR-proADM and increases thereof were associated with ICU admission suggesting the potential as a prognostic factor for severe pediatric LRTI. MR-proADM might only bear limited value for decision making on stopping antibiotics due to its slow decrease. Copeptin had no added value in our setting.

Assessment of the state and relationship of vasopressor and renin-angiotensin systems in patients with localized kidney cancer on the background of arterial hypertension

Background. Vasopressin, in cooperative interaction with angiotensin II, participates in cardiovascular regulation and it increases in arterial hypertension. In addition, vasopressin is involved in tumorigenesis through angiogenesis by stimulating protein synthesis in endothelial cells, induction of endothelin-1, influencing cell proliferation, and stimulating growth factors through VIA receptors in the kidneys. To assess the content of vasopressin, a measurement of copeptin, its precursor, produced in an equimolar ratio, is used.Objective: to determine the content of serum copeptin and to reveal correlations with the indices of the renin-angiotensin system in the tumor and blood serum in patients with localized kidney cancer (КС) with arterial hypertension (AH).Materials and methods. The inclusion criteria for the study were initially diagnosed localized KC T1N0M0 without special treatment, age less than 75 years, essential AH of I—II degree without treatment, controlled by angiotensin-converting enzyme inhibitors (ACEi). All patients were divided into groups: patients with KC (n = 42); KC + AH without treatment (n = 31); KC + AH + ACEi (n = 32). Serum levels of copeptin and angiotensin I, II, 1-7 and angiotensin-converting enzyme, angiotensin-converting enzyme 2 were determined by ELISA. Also, the level of components of the renin-angiotensin system was assessed in tumor tissue samples obtained by robotic-assisted kidney resection.Results and conclusion. In patients of the KC + AH group, the median of the indicator is statistically significantly higher than in the group of healthy donors (2.4 times at p &lt;0.05). In the group KC + AH + ACEi, a decrease in the content of the studied indicator was found in comparison with the norm by 1.2 times (at p &lt;0.05). It was found that the content of copeptin in the tumor less than 4 cm in comparison with the size of 4-7 cm is significantly lower (KC p = 0.045, KC + AH p = 0.067 and KC + AH + ACEi p = 0.036). Correlation analysis showed direct significant links between high density between the levels of copeptin and angiotensin II in the tumor and blood, and moderate tightness with tumor and serum levels of angiotensin (1-7). Multiple regression analysis revealed that the most significant factors that have a positive effect on the concentration of serum copeptin are the content of angiotensin II in the tumor and blood serum, the tumor concentration of angiotensin (1-7) and angiotensin-converting enzyme 2, as well as the level of systolic blood pressure (p &lt;0.05).

Effects of exercise on serum ischemia-modified albumin, brain natriuretic peptide and copeptin levels in boxers and kick boxers.

Introductionboxing and kick boxing are combat sports that can cause severe head, neck, face and hand injuries during fighting. Then, traumatic brain injury (TBI) incidence is high in these sports. Ischemia-modified albumin (IMA), brain natriuretic peptide (BNP) and copeptin have diagnostic and prognostic value for cardiac and non-cardiac ischemic events. The purpose of this study is to evaluate exercise-induced variations of serum IMA, BNP and copeptin.Methodstwenty male boxers, twenty-three male kick boxers and twenty-three age-matched male were enrolled in the study. Health assessment data were analysed. Boxers and kick boxers underwent an exercise program including training plus fighting matches. Serum samples were collected in the pre- and post-exercise periods. Serum IMA, BNP and copeptin concentrations were measured in these specimens using ELISA reagents.Resultscomparative analysis of analytes before and after exercise showed that exercise significantly increased serum IMA, BNP and copeptin levels both in boxers and kick boxers.Conclusionin conclusion, IMA, BNP and copeptin levels may be candidate biomarkers for exercise-related traumatic brain injuries. The identification of new biomarkers in patients with acute and chronic neurological disorders is of considerable interest to clinicians. Then, further studies should be conducted to evaluate the possible role of IMA, BNP and copeptin in TBI pathophysiology.

MARKER DIAGNOSTIC HEART FAILURE PROGRESSION IN THE POST-INFARCTION PERIOD.

The aim: To study the relationship between the concentration of copeptin, NT-proBNP, ST2 and indicators of myocardial remodeling, the dynamics of these indicators in order to predict the occurrence of decompensated heart failure (HF) in patients with acute myocardial infarction (AMI). Materials and methods: The study is based on the results of the examination of 160 patients with MI, including 120 patients with decompensated CHF II A-B stage according to Vasylenko-Strazhesko classification of (FC) III-IV (according to NYHA) and 40 patients with MI without signs of decompensated CHF, as well as 20 medically healthy individuals. The level of copeptin, NT-proBNP, ST2 were determined. Results: In patients with signs of decompensated HF there were significantly higher levels of NT-proBNP in the blood serum that amounted to (950.38±3.15) pg/ml, in patients without decompensated HF after MI (580.15±3.03) pg/ml compared to healthy individuals (111.20±3.47) pg/ml (p<0.05). The mean value of copeptin concentration in patients with decompensated CHF was recorded (18.11±0.12) pg/ml, compared to (12.03±0.14) pg/ml in patients with MI without signs of CHF decompensation. Conclusions: The most significant for clinical and prognostic assessment of the post-infarction period complicated by decompensated HF is the response of the patient's body to dosed physical exertion and the levels of NT-prpBNP, copeptin and ST2.