Plasma Copeptin Concentrations Research Articles

Plasma Glial Fibrillary Acidic Protein, Copeptin, and Matrix Metalloproteinase-9 Concentrations among West African Stroke Subjects Compared with Stroke-Free Controls

Measurement of plasma molecular markers among stroke patients has been proposed as an avenue for improving the accuracy of stroke diagnosis. There is paucity of data on the potential role of these markers in resource-limited settings, where the burden of stroke is greatest. To assess the potential diagnostic and prognostic performance of 3 proposed biomarkers for stroke in a resource-constrained setting. Consecutive stroke subjects presenting at a tertiary medical center in Kumasi, Ghana, with radiologically confirmed diagnosis and etiologic subtype information available were recruited along with age- and gender-matched controls in a 2:1 ratio. Plasma concentrations of glial fibrillary acidic protein (GFAP), copeptin, and matrix metalloproteinase-9 (MMP-9) among stroke patients and stroke-free controls were measured in duplicates using enzyme linked immunoassays. Diagnostic and prognostic correlates were assessed using area-under-the-curve (AUC) measures of receiver operator curves and logistic regression analysis, respectively. There were 156 stroke subjects with a mean age of 61.3 years of which 47.4% were females and 74 age- and gender-matched stroke-free controls. Median (interquartile range) time from symptom onset to hospital presentation for care was 7 days (5-11). Diagnostic accuracy of a single measurement of the 3 biomarkers for stroke using AUC (95% confidence interval) plots were as follows: .84 (.77-0.91), P < .0001, for GFAP; .85 (.79-0.92), P < .0001, for copeptin; and .65 (.56-0.73), P = .0003, for MMP-9. None of the biomarkers was associated with stroke severity or mortality. Plasma concentrations of GFAP and copeptin demonstrated stronger associations with stroke occurrence in this West African cohort compared with controls.

An exploratory pilot study with copeptin as a biomarker for individualizing treatment for nocturnal polyuria.

The aim of the present study was to investigate the use of random copeptin concentrations as possible biomarkers for the differential diagnosis of nocturnal polyuria (NP). In all, 111 patients with and without nocturia were enrolled in the study. Patients with a neurogenic bladder and/or those who had undergone bladder or urethral surgery were excluded from the study. All patients completed a 72-hour frequency-volume chart and a renal function profile. A random blood sample was obtained during the day for measurement of plasma copeptin concentrations, osmolality, and serum sodium and creatinine concentrations. The effect of the use of different definitions for NP was evaluated. The median age of the study participants was 61 years, and 48% were female. Copeptin was significantly correlated with urinary and plasma osmolality, as well as free water clearance (r=0.43, 0.56 and -0.38 respectively; P < .001 for all). Study participants were divided into 3 groups: controls (n = 51), those with NP (n = 41), and those with global polyuria (n = 19). Copeptin concentrations were significantly lower in subjects with global polyuria than in those with NP and the control group (2.96 vs 3.97 and 3.94 pM, respectively; P = .008 and .005). There was no significant difference in random daytime copeptin concentrations between the NP and control groups (P = .972). The results differed when other definitions for NP were used (e.g. NPi33 or NUP10). We could not confirm our hypothesis that patients with NP have lower copeptin concentrations, although random blood sampling is not ideal. Further research is required to determine the use of copeptin in NP, perhaps in the identification of the desmopressin response.

Comparison of plasma copeptin and multiple biomarkers for assessing prognosis of patients with aneurysmal subarachnoid hemorrhage

BackgroundIncreased plasma copeptin concentrations are related to poor prognosis after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess prognostic significance of plasma copeptin detection compared with glial fibrillary astrocyte protein, myelin basic protein, S100B, phosphorylated axonal neurofilament subunit H, neuron-specific enolase, tau and ubiquitin carboxyl-terminal hydrolase L1 in aSAH. MethodsWe detected plasma concentrations of the aforementioned biomarkers in 105 healthy controls using ELISA. Their predictive ability for symptomatic cerebral vasospasm and 6-month poor outcome (Glasgow Outcome Scale score of 1–3) were compared. ResultsPlasma concentrations of the preceding biomarkers were highly correlated with World Federation of Neurological Surgeons subarachnoid hemorrhage scale (WFNS) scores as well as were significantly higher in patients with symptomatic cerebral vasospasm than in those without symptomatic cerebral vasospasm and in patients with poor outcome than in those with good outcome. In terms of area under receiver operating characteristic curve, their predictive value for symptomatic cerebral vasospasm and 6-month poor outcome was in the range of WFNS scores. Plasma copeptin concentration, but not plasma concentrations of other biomarkers, statistically significantly improved the predictive performance of WFNS scores. ConclusionsCopeptin in plasma might have the potential to be a useful prognostic biomarker for aSAH.

Vasopressin and diabetic nephropathy

The prevalence of diabetic kidney disease (DKD) is increasing worldwide. Despite major therapeutic advances in the last decades in DKD, the current standard of care let many people progress to severe stages. Vasopressin secretion is increased in diabetes, and its potential role in the onset and progression of DKD is being re-investigated. Recently, observational studies evidenced an association between surrogates of vasopressin secretion (daily fluid intake or urine volume, and plasma copeptin concentration) and chronic kidney disease in the community, but also specifically in type 1 and in type 2 diabetes. Causality is strongly supported by a series of studies in rats conducted more than a decade ago, and by additional recent experimental data. The mechanism underlying these adverse effects likely involves the hyperfiltration induced indirectly as a consequence of the tubular effects of the hormone mediated by the V2 receptor. If chronic vasopressin action on the kidney is detrimental in diabetes as suggested so far, intervention studies should be designed. Available tools include V2 receptor blockade, and changes in daily water intake in vulnerable patients. Safety and effectiveness should be tested, as it is currently done in patients with CKD (NCT01766687).

Copeptin and NT-proBNP for prediction of all-cause and cardiovascular death in ischemic stroke.

To evaluate long-term mortality in patients with acute ischemic stroke (AIS) by exploring the correlation between death and plasma concentrations of copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a cohort study. In a prospective, multicenter observational study of 4,215 patients with AIS, copeptin and NT-proBNP levels were measured with a standardized method when patients were admitted to hospital. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality within 1 year. During a follow-up period, 906 patients (20.1%, 95% confidence interval [CI] 18.9-21.2) died, including 589 cases of CVD mortality (13.1%, 95% CI 12.1-14.0). With the use of a multivariate analysis, both markers were found to have prognostic value in the same model (CVD mortality: odds ratio [OR] for fourth quartile of copeptin and NT-proBNP 1.68 and 2.58, 95% CI 1.22-2.49 and 1.76-4.05, respectively; all-cause mortality: OR for fourth quartile of copeptin and NT-proBNP 1.48 and 2.47, 95% CI 1.22-2.03 and 1.68-3.95, respectively). In a receiver operating characteristics analysis of CVD mortality, the area under the curve varied from 0.80 to 0.83 (95% CI 0.79-0.87) when the index of NT-proBNP was added and increased to 0.86 (95% CI 0.83-0.90) when both markers were added. Copeptin and NT-proBNP may be useful independent prognostic markers of all-cause or CVD mortality in Chinese patients with AIS.

Comparative evaluation of copeptin and NT-proBNP in patients with severe acute decompensated heart failure, and prediction of adverse events in a 90-day follow-up period: A prospective clinical observation trial.

The present study compared the prognostic value of a marker, the C-terminal section of the arginine vasopressin prohormone (copeptin), with N-terminal B-type natriuretic peptide (NT-proBNP) in patients with severe acute decompensated heart failure. A prospective, observational cohort study was conducted in a tertiary care hospital and enrolled 129 patients with severe acute decompensated heart failure. Clinicians were blinded to investigational markers except NT-proBNP, and the study participants were followed up for 90 days. The end-point was a composite of cardiovascular death or re-hospitalization due to decompensated heart failure. Of the 129 patients enrolled, 47 reached the end-point and 82 were in a stable condition during follow-up. Receiver operating characteristic curve analysis revealed that the areas under curve for the prediction of adverse events within 90 days were similar for copeptin [0.602±0.052; 95% confidence interval (CI), 0.499-0.705], NT-proBNP (0.659±0.048; 95% CI, 0.565-0.753) and their combination (0.670±0.050; 95% CI, 0.573-0.767). Kaplan-Meier survival analysis showed that the predictive value of NT-proBNP regarding the probability of survival was superior compared with that of copeptin (log-rank test for trend, P=0.001 vs. 0.040). Furthermore, multivariate Cox proportional-hazards regression analysis revealed that increased NT-proBNP and copeptin plasma concentrations were significant independent predictors of adverse events. The present study provided evidence that copeptin has similar predictive properties compared with NT-proBNP regarding adverse events within 90-days in patients with severe acute decompensated heart failure, but that copeptin may not provide superior 90-day prediction compared to NT-proBNP.

Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines.

Hyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status. Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach. The treatment for hyponatremia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia, both guidelines adopted the approach of giving a bolus of hypertonic saline. Although fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary. Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in the two guidelines. Such discrepancies may relate to different interpretations of the limited evidence or differences in guideline methodology. Nevertheless, the development of guidelines has been important in advancing this evolving field.

The Chronic Kidney Disease Water Intake Trial: Protocol of a Randomized Controlled Trial.

Background:In observational studies, drinking more water associates with a slower rate of kidney function decline; whether the same is true in a randomized controlled trial is unknown.Objective:To examine the 1-year effect of a higher vs usual water intake on estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease.Design:Parallel-group randomized controlled trial.Setting:Nine centers in Ontario, Canada. Enrollment and randomization occurred between May 2013 and May 2016; follow-up for the primary outcome will continue until June 2017.Participants:Adults (n = 631) with stage 3 chronic kidney disease (eGFR 30-60 mL/min/1.73 m2) and microalbuminuria.Intervention:The high water intake group was coached to increase their oral water intake by 1.0 to 1.5 L/day (depending on sex and weight), over and above usual consumed beverages, for a period of 1 year. The control group was coached to maintain their usual water intake during this time.Measures:Participants provided 24-hour urine samples at baseline and at 6 and 12 months after randomization; urine samples were analyzed for volume, creatinine, osmolality, and the albumin-to-creatinine ratio. Blood samples were obtained at baseline and at 3- to 6-month intervals after randomization, and analyzed for creatinine, copeptin, osmolality, and electrolytes. Other measures collected included health-related quality of life, blood pressure, body mass index, and diet.Primary outcome:The between-group change in eGFR from baseline (prerandomization) to 12 months after randomization.Secondary outcomes:Change in plasma copeptin concentration, 24-hour urine albumin-to-creatinine ratio, measured creatinine clearance, estimated 5-year risk of kidney failure (using the 4-variable Kidney Failure Risk Equation), and health-related quality of life.Planned analysis:The primary analysis will follow an intention-to-treat approach. The between-group change in eGFR will be compared using linear regression. Supplementary analyses will examine alternative definitions of eGFR change, including annual percentage change, rate of decline, and rapid decline (a P value <0.05 will be interpreted as statistically significant if there is concordance with the primary outcome).Trial Registration:This randomized controlled trial has been registered at www.clinicaltrials.gov; government identifier: NCT01766687.

Elevated plasma levels of copeptin linked to diabetic retinopathy in type 2 diabetes

BackgroundThe arginine vasopressin (AVP) system has been postulated to play a role in glucose homeostasis, insulin resistance, and diabetes mellitus in human and animal studies. The aim of this study was to evaluate the role of plasma copeptin in Chinese patients with type 2 diabetes mellitus (T2DM) with and without diabetic retinopathy (DR). MethodPlasma copeptin concentrations were determined in 281 patients with T2DM. At baseline, demographic and clinical information including presence of DR and vision-threatening DR (VTDR) was collected. The relationship between copeptin and DR or VTDR was investigated using logistic regression. ResultsT2DM participants with DR or VTDR had significantly higher plasma copeptin concentrations on admission (P < 0.0001). Receiver operating characteristics to predict DR and VDTR demonstrated areas under the curve for copeptin of 0.784 (95% confidence interval [CI] 0.724–0.844) and 0.834 (95% CI 0.781–0.904), respectively, which were superior to those for the homeostasis model assessment of insulin resistance (DR AUC 0.736, 95% CI 0.676–0.797; VTDR AUC 0.754, 95% CI 0.703–0.828; P < 0.01). Multivariate logistic regression analysis adjusted for common DR risk factors showed plasma copeptin concentrations ≥28.6 pmol/L (>3rd quartile) to be an independent marker of DR (OR 3.68, 95% CI 2.04–6.79; P < 0.0001) and VTDR (OR 4.32, 95% CI 2.12–8.14; P < 0.0001). ConclusionsWe found that increased plasma copeptin concentrations were an independent marker of DR and VDTR in Chinese patients with T2DM, suggesting a possible role of copeptin in the pathogenesis of DR complications.

Fetal Release of Copeptin in Response to Maternal Oxytocin Administration: A Randomized Controlled Trial.

To test whether an oxytocin challenge test raises neonatal levels of copeptin, the C-terminal portion of proarginine vasopressin, a sensitive stress marker elevated in neonates born by vaginal delivery as opposed to elective cesarean delivery. In a randomized controlled trial in women with a singleton pregnancy undergoing elective cesarean delivery at greater than 36 weeks of gestation and no contractions or rupture of membranes, we compared arterial umbilical cord plasma concentrations of copeptin between neonates exposed to an oxytocin challenge test before elective cesarean delivery and those administered saline infusion (placebo group). Women randomized to an oxytocin challenge test received 5 international units/500 mL oxytocin Ringer lactate infused at a rate of 12 mL/h and doubled every 10 minutes until it induced three uterine contractions per 10-minute interval, at which point it was discontinued. Neonatal copeptin levels were the primary endpoint. Secondary endpoints included biochemical and physiologic parameters of fetal and maternal well-being. From January 2012 to October 2012 and from September 2013 to January 2015, 78 women underwent an oxytocin challenge test and 78 placebo infusion, of whom 12 and 11, respectively, were excluded as a result of insufficient blood sample volume for analysis. Umbilical cord plasma copeptin levels [median (range)] were higher in neonates who underwent an oxytocin challenge test than those who underwent placebo infusion: 22.2 (3.22-2,319) compared with 7.39 (2.5-344.6) pmol/L (P<.001). There were no statistically significant differences between the two groups in secondary outcomes. Oxytocin challenge test-induced contractions before elective cesarean delivery trigger fetal copeptin release. ClinicalTrials.gov, https://clinicaltrials.gov, NCT01962701.

OP.7D.02] INCREASE IN PLASMA COPEPTIN CONCENTRATION IN PATIENTS WITH CONFIRMED RESISTANT ESSENTIAL HYPERTENSION

Objective: The lack of consensus regarding the role of vasopressin in uncontrolled hypertension may be due to the use of assays with limited sensitivity. We used plasma copeptin concentration (PCop), a reliable surrogate marker for plasma vasopressin, to evaluate its role in a large population of patients with resistant (RH) and non-resistant (NRH) essential hypertension. Design and method: 166 patients with RH to > = 3 antihypertensive drugs, including a diuretic (office BP > = 140 or 90 mmHg), entered a 4-week standardized treatment with irbesartan 300 mg + HCTZ 12.5 mg + amlodipine 5 mg to confirm RH by ABPM (daytime ambulatory BP > = 135/85 mmHg). We compared PCop, plasma renin (PRC) and aldosterone concentration (PAC) and urine osmolality (Uosm) and estimated glomerular filtration rate (eGFR) after 4 weeks between patients with confirmed RH (n = 140) and NRH (n = 26). Results: Patients with RH were more frequently men, had significantly lower PRC, but similar PAC than patients with NRH. PCop was about 2-fold higher in patients with RH than in those with NRH (P = 0.001 adjusted on sex, plasma Na, daytime SBP and eGFR) even though similar plasma Na (p = 0.9). RH Uosm, 24-h and urinary output and correlation between Uosm log-PCop did not significantly differ between the two groups.Conclusions: Patients with RH to a 4-week standardized triple therapy had a 2-fold lower PRC (indicating a persistance of volume expansion) and a 2-fold higher PCop than those of patients NRH. The increase in PCop was not explained by changes in plasma Na, nor by peripheral (renal) resistance to vasopressin. This suggests a primary central stimulation of AVP secretion in RH associated with biological signs of volume expansion.

Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short-term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD. These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249-1264).

Atrial natriuretic peptide, copeptin and adrenomedullin levels in polycystic ovary syndrome: a case-control study

Background: Polycystic ovary syndrome (PCOS) defined by the Rotterdam criteria does not take into account the unhealthy metabolic profile of the syndrome with increased insulin resistance (IR) and overweight favoring development of type 2 diabetes, hypertension and cardiovascular disease (CVD). We assess three vasoactive peptides associated with CVD in women with PCOS.Method: Plasma levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin and mid-regional pro-adrenomedullin (MR-proADM) were measured in 98 PCOS patients and 46 age- and BMI-matched healthy women.Results: We found no difference in levels of MR-proANP, copeptin and MR-proADM between the PCOS and control group. Multiple regression analyses on a combined group of PCOS and control subjects demonstrated an inverse correlation between MR-proANP and IR (measured by fasting C-peptide) and a positive correlations between copeptin and IR as well as MR-proADM and BMI. We found no association between peptide levels and different Rotterdam phenotypes.Conclusion: Plasma concentrations of MR-proANP, copeptin and MR-proADM were not increased in PCOS compared to age- and BMI-matched controls. Thus, these peptides cannot be used to detect increased risk of CVD in a young PCOS cohort.

Does plasma copeptin level at admission predict final infarct size in ST-elevation myocardial infarction

BackgroundCopeptin is a novel biomarker of potential diagnostic and prognostic value in patients with ST-elevation myocardial infarction (STEMI). This study was conducted to investigate the relationship between plasma copeptin levels at admission and final infarct size in STEMI patients. Materials and methodsThis observational study was conducted in Sher-i-Kashmir Institute of Medical sciences, Srinagar, for a period of 1year. 60 patients with STEMI admitted within 24h of symptom onset were included in the study. Plasma copeptin concentrations were determined by ELISA from blood samples drawn at the time of admission. Infarct size was estimated on cardiac MRI after 5–14days of admission, in successfully reperfused patients. Correlations between plasma copeptin levels, infarct size and various clinico-hemodynamic variables were studied. ResultsPlasma copeptin concentrations showed a significant positive correlation with MRI determined infarct size (r=0.957; p≤0.0001). Copeptin levels were significantly higher in patients with anterior wall infarction (p≤0.0001), longer symptom duration (p=0.018), advanced Killip class (p≤0.0001), higher body mass index (p=0.019) and extensive coronary artery disease (p≤0.0001). On multivariate analysis, copeptin levels at admission independently predicted final infarct size, irrespective of the clinico-hemodynamic profile of patients or mode of reperfusion (p≤0.0001). The only independent predictor of copeptin level was symptom duration (p=0.018). ConclusionCopeptin level at admission predicts final infarct size in STEMI patients. Further evidence is however needed before implementation of this biomarker into routine clinical practice.

Galectin 3: association to neurohumoral activity, echocardiographic parameters and renal function in outpatients with heart failure.

BackgroundGalectin 3 (Gal-3) reflects cardiac fibrosis in heart failure HF, but has also been associated to renal fibrosis and impaired renal function. Previous research has suggested that Gal-3 could be a cardio-renal biomarker, but it has never been tested simultaneous in a single study whether Gal-3 reflects echocardiographic measures, neurohumoral activity and renal function.The aim of this study was to evaluate the relationship between plasma concentrations of Gal-3 and neurohumoral activity, myocardial and renal function in patients with HF, including advanced echocardiographic measures and 24-h urinary albumin excretion (albuminuria).MethodsWe prospectively enrolled 132 patients with reduced left ventricular ejection fraction (LVEF) referred to an outpatient HF clinic. The patients had a median age of 70 years (interquartile rage: 64–75), 26.5 % were female, median LVEF was 33 % (27–39 %) and 30 % were in NYHA class III-IV.ResultsPatients with plasma concentrations of Gal-3 above the median had significantly lower estimated glomerular filtration rate (eGFR) and this association remained significant in multivariate regression analysis (β: −0.010; 95 % CI −0.012–-0.008; P < 0.001), adjusted for age, gender, medical treatment. Plasma concentrations of Gal-3 were not associated with albuminuria (Beta: 0.008; 95 % CI:-0.028–0.045; P = 0.652). There were no association between plasma concentrations of Gal-3 and myocardial function or structure estimated by LVEF, LVmassIndex, LVIDd, E/é or LV global longitudinal strain (P > 0.05 for all). In multivariate analyses plasma concentrations of Gal-3 were significantly associated with the cardiac biomarkers: NT-proBNP (β: 0.047; 95 % CI: 0.008–0.086; P = 0.020), proANP (β: 0.137; 95 % CI: 0.067–0.207; P < 0.001), chromogranin A (β: 0.123; 95 % CI: 0.052–0.194; P < 0.001) and Copeptin (β: 0.080; 95 % CI: 0.000–0.160; P = 0.049). Multivariate analysis was adjusted for eGFR, age, gender and medical treatment.ConclusionsIncreased plasma concentrations of Gal-3 are associated with reduced eGFR and increased plasma concentrations of NT-proBNP, proANP, chromogranin A and Copeptin, but not with echocardiographic parameters reflecting myocardial function. These results suggest that Gal-3 reflects both increased neurohumoral activity and reduced eGFR, but not myocardial function in patients with systolic HF.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0290-7) contains supplementary material, which is available to authorized users.

Regional circulatory distribution of novel cardiac bio-markers and their relationships with haemodynamic measurements

BackgroundRegional sampling may identify sites of production or removal of novel biomarkers in the circulation; their relationship to haemodynamic measurements may clarify their association with the pathophysiology of heart failure. MethodsSamples were obtained from up to eight circulatory sites from 22 patients with left ventricular dysfunction undergoing elective cardiac catheterisation. The plasma concentrations (PC) of six biomarkers [mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), mid-regional pro-adreno-medullin (MR-proADM), high sensitivity pro-calcitonin (hsPCT), copeptin and galectin-3 (Gal-3)] were measured. ResultsPlasma concentrations of MR-proANP were highest in the pulmonary artery (PA) and left ventricle, suggesting myocardial production. Lower concentrations of copeptin, CT-proET-1, MR-proADM and hsPCT were found in the supra-renal inferior vena cava (SRIVC) sample suggesting renal extraction. Plasma concentrations of Galectin-3 varied little by sampling site. Plasma concentrations of MR-proANP (R=0.69, P=0.002), MR-proADM (R=0.51, P=0.03), CT-proET-1 (R=0.60, P=0.009) and Copeptin (R=0.47, P<0.05) measured from PA samples correlated with PA systolic pressure. There was no relation between any measured marker and cardiac index. ConclusionsRegional sampling shows variation in the plasma concentration of various novel peptides that provides clues to sites of net production and removal. Plasma concentrations of several biomarkers were positively correlated with pulmonary artery pressure.

Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis.

Copeptin and arginine vasopressin (AVP) are derived from a common precursor molecule and have equimolar secretion and response to osmotic, haemodynamic and stress-related stimuli. Plasma concentrations of copeptin and AVP in relation to serum osmolality are highly correlated. The physiological functions of AVP with respect to homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response are well known, but the exact function of copeptin is undetermined. Quantification of AVP can be difficult, but copeptin is stable in plasma and can be easily measured with a sandwich immunoassay. For this reason, copeptin has emerged as a promising marker for the diagnosis of AVP-dependent fluid disorders. Copeptin measurements can enable differentiation between various conditions within the polyuria-polydipsia syndrome. In the absence of prior fluid deprivation, baseline copeptin levels >20 pmol/l identify patients with nephrogenic diabetes insipidus. Conversely, copeptin levels measured upon osmotic stimulation differentiate primary polydipsia from partial central diabetes insipidus. In patients with hyponatraemia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, and the ratio of copeptin to urinary sodium can distinguish the syndrome of inappropriate antidiuretic hormone secretion from other AVP-dependent forms of hyponatraemia.

Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder.

Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus–pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS.

Effect of increased water intake on plasma copeptin in patients with chronic kidney disease: results from a pilot randomised controlled trial

ObjectivesIncreased water intake may have a beneficial effect on the kidney through suppression of plasma vasopressin. We examined the effect of increased water intake on plasma copeptin (a marker of...

Plasma copeptin for short term risk stratification in acute pulmonary embolism.

Copeptin (COP) was reported to have prognostic value in various cardiovascular diseases. We hypothesized that COP levels reflect the severity of acute pulmonary embolism (PE) and may be useful in prognostic assessment. Plasma COP concentrations were measured on the Kryptor Compact Plus platform (BRAHMS, Hennigsdorf, Germany). The study included 107 consecutive patients with diagnosed acute PE (47 males, 60 females), with median age of 65 years (range 20-88). High risk PE was diagnosed in 3 patients (2.8 %), intermediate risk in 69 (64.5 %), and low risk PE in 35 (32.7 %) patients. Control group included 64 subjects (25 males, 39 females; median age 52.5 year, range 17-87). Four patients (3.7 %) died during 30-day observation. Complicated clinical course (CCC) was experienced by 10 (9.3 %) patients. COP level was higher in PE patients than in controls [11.55 pmol/L (5.16-87.97), and 19.00 pmol/L (5.51-351.90), respectively, p < 0.0001], and reflected PE severity. COP plasma concentration in low risk PE was 14.67 nmol/L (5.51-59.61) and in intermediate/high risk PE 19.84 mol/L (5.64-351.90) p < 0.05. Median COP levels in nonsurvivors was higher than in survivors, 84.6 (28.48-351.9) pmol/L and 18.68 (5.512-210.1) pmol/L, respectively, p = 0.009. Subjects with CCC presented higher COP levels than patients with benign clinical course 53.1 (17.95-351.9) pmol/L and 18.16 (5.51-210.1) pmol/L, respectively, p = 0.001. Log-transformed plasma COP was the significant predictor of CCC, OR 16.5 95 % CI 23.2-111.9, p < 0.001. AUC-for prediction of CCC using plasma COP was 0.811 (95 % CI 0.676-0.927). The COP cut off value of 17.95 nmol/l had sensitivity of 100 %, specificity 49.5 %, positive predictive value of 16.9 % and negative predictive value of 100 %. We conclude that plasma COP levels can be regarded for promising marker of severity of acute PE and show potential in risk stratification of these patients.