Plasma Copeptin Concentrations Research Articles

Copeptin and MR-proADM in Umbilical Cord Plasma Reflect Perinatal Stress in Neonates Born to Mothers with Diabetes and MR-proANP Reflects Maternal Diabetes

To examine concentrations of three cardiovascular propeptides in umbilical cord plasma of neonates born to mothers with Type 1, Type 2 and gestational diabetes. Measurement of cardiovascular markers in umbilical cord plasma may potentially help identify neonates at risk of postnatal complications. Neonates born to mothers with diabetes have an increased risk of neonatal morbidity and mortality, and measurement of these new biomarkers may potentially help identify neonates at risk of these complications. Copeptin, midregional proadrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) were measured in cord plasma of neonates (n = 63) born to mothers with the three types of diabetes. Associations with maternal glycemic control, mode of delivery and neonatal metabolic acidosis were examined. Umbilical cord plasma copeptin concentrations were lowest in neonates after elective cesarean sections (6.1 pmol/l; interquartile range [IQR]: 4.5-9.1) compared with emergency cesarean sections (156 pmol/l; IQR: 9.6-311; p = 0.019) and vaginal delivery (831 pmol/l; IQR: 107-2407; p < 0.0001). MR-proADM was also affected by mode of delivery; however, this seemed more likely to be caused by an inverse association with the acid-base balance. In this population, only MR-proANP plasma concentrations were related to type of diabetes. Neonates born to mothers with Type 1 diabetes had higher concentrations (median 260 pmol/l; IQR: 222-318) compared with Type 2 diabetes (175 pmol/l; IQR: 169-200; p = 0.003) and gestational diabetes (200 pmol/l; IQR: 149-276; p = 0.009). Umbilical cord plasma copeptin and MR-proADM concentrations primarily reflect perinatal stress associated with mode of delivery and the degree of fetal acidosis, whereas MR-proANP concentrations are higher in neonates born to mothers with Type 1 diabetes.

Plasma copeptin levels in Chinese patients with acute ischemic stroke: a preliminary study

Copeptin is a stable by-product of arginine-vasopressin synthesis and reflects its secretion. The objective of the study was to evaluate the predictive value of copeptine on functional outcome at 90-day follow-up from stroke onset. We conducted a prospective, observational cohort study in the emergency department of two hospitals and enrolled 125 patients with acute ischemic stroke. Plasma copeptin concentrations, determined by a CT-proAVP-luminescence-immunoassay, were measured. There was a good correlation between levels of plasma copeptin and NIHSS score (r = 0.733, P < 0.01). In the 41 patients (32.8 %) with a poor functional outcome, copeptin levels were higher compared with those in patients with a favorable outcome (27.3; IQR, 14.9-34.8 pmol/L vs. 12.9; IQR, 9.4-21.6 pmol/L; P < 0.0001). Copeptin levels in 18 patients who died were more than two times greater as compared to patients who survived (32.4; IQR, 18.7-38.5 pmol/L vs. 15.1; IQR, 12.4-24.6 pmol/L; P < 0.0001). After adjusting for all other significant outcome predictors, copeptin level remained an independent predictor for poor functional outcome and mortality with an odds ratio of 3.12 (95 % CI 1.54-6.46), 3.16 (95 % CI 0.92-6.15), respectively. Our study suggests that copeptin levels are a useful tool to predict outcome and mortality 3 months after acute ischemic stroke and have a potential to assist clinicians.

Copeptin is a predictive biomarker of severity in acute pancreatitis

BackgroundAcute pancreatitis remains a common intraabdominal disease with a complex pathophysiology. The overall outcome has improved, but specific treatment remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of copeptin in the initial phase of predicted severe acute pancreatitis. MethodsBetween August 2008 and December 2011, 57 patients with acute pancreatitis and 30 healthy individuals were included in the study. Four blood samples, for serum copeptin measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent 3 samples were taken at 12, 24, and 48 hours after the onset of pain. ResultsCopeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients. ConclusionsCopeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients.

Determinants of plasma copeptin: A systematic investigation in a pediatric mechanical ventilation model

Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, holds promise as a diagnostic and prognostic plasma biomarker in various acute clinical conditions. Factors influencing copeptin response in the critical care setting are only partially established and have not been investigated systematically. Using an in vivo infant ventilation model (Wistar rats, 14 days old), we studied the influence of commonly occurring stressors in critically ill children. In unstressed ventilated rats basal median copeptin concentration was 22pmol/L. In response to respiratory alkalosis copeptin increased 5-fold, while exposure to hypoxemia, high PEEP, hemorrhage, and psycho-emotional stress produced a more than 10-fold increase. Additionally, we did not find a direct association between copeptin and acidosis, hypercapnia, and hyperthermia. Clinicians working in the acute critical care setting should be aware of factors influencing copeptin plasma concentrations. Moreover, our results do have implications for animal studies in the field of stress research.

Copeptin as a marker of relative arginine vasopressin deficiency after pediatric cardiac surgery

Relative arginine vasopressin (AVP) deficiency after pediatric cardiac surgery has recently been described. Copeptin, a more stable and easily measured product of pro-AVP processing, may be a means of identifying these patients. We aimed to determine if copeptin was correlated with AVP in these children and whether it can be a surrogate marker of relative AVP deficiency. Patients <6 years of age with basic Aristotle scores ≥7 requiring surgery with cardiopulmonary bypass were prospectively enrolled. Plasma AVP and copeptin concentrations were measured pre-cardiopulmonary bypass and 4 and 24 h post-cardiopulmonary bypass. Relative AVP deficiency was defined a priori based on our previous work as AVP <9.2 pg/ml at 4 h post-cardiopulmonary bypass. Of 41 children enrolled, relative AVP deficiency was present in 13 (32 %). AVP and copeptin concentrations were significantly lower in these 13 children at 4 h post-cardiopulmonary bypass as compared to the other 28 patients. A significant positive association between plasma AVP and copeptin concentrations over time was determined. Based on log-transformed analyses, a 1 % increase in plasma AVP led to a 0.19 % increase in copeptin. Further, copeptin <1.12 ng/ml at 4 h post-cardiopulmonary bypass had a sensitivity of 92 % and a negative predictive value of 95 % for relative AVP deficiency. Plasma AVP and copeptin are positively associated in children undergoing cardiac surgery. Copeptin may represent a useful means of identifying relative AVP deficiency in these patients.

Relationship of Copeptin, a Surrogate Marker for Arginine Vasopressin, With Change in Total Kidney Volume and GFR Decline in Autosomal Dominant Polycystic Kidney Disease: Results From the CRISP Cohort

Experimental studies indicate that arginine vasopressin (AVP) may have deleterious effects in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, the significance of AVP in human ADPKD is unclear. Longitudinal observational study with 8.5 (IQR, 7.7-9.0) years' follow-up (CRISP [Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease]). 241 patients with ADPKD with creatinine clearance >70 mL/min. Plasma copeptin concentration, a surrogate marker for AVP. Change in measured glomerular filtration rate (mGFR, assessed by iothalamate clearance) and total kidney volume (measured by magnetic resonance imaging). Baseline copeptin level, plasma and urinary osmolality, and measurements of total kidney volume and mGFR during follow-up. In these patients (median age, 34 [IQR, 25-40] years; 38% men; median mGFR, 94 [IQR, 79-145] mL/min/1.73 m(2); median total kidney volume, 859 [IQR, 577-1,299] mL), median copeptin level was 2.9 (IQR, 1.8-5.1) pmol/L. Copeptin was not associated with plasma osmolality (P = 0.3), the physiologic stimulus for AVP release, but was associated significantly with change in total kidney volume during follow-up (P < 0.001). This association remained significant after adjusting for sex, age, cardiovascular risk factors, and diuretic use (P = 0.03). Copeptin level was associated borderline significantly with change in mGFR after adjusting for these variables (P = 0.09). No standardization of hydration status at time of copeptin measurement. These data show that in ADPKD, copeptin level, as a marker for AVP, is not correlated with plasma osmolality. Most importantly, high copeptin levels are associated independently with disease progression in early ADPKD. This is in line with experimental studies that indicate a disease-promoting role for AVP.

Copeptin is associated with one-year mortality and functional outcome in patients with acute spontaneous basal ganglia hemorrhage

High plasma copeptin levels have been found to be associated with short-term poor outcome after intracerebral hemorrhage (ICH). We furthermore evaluate the relation of plasma copeptin levels to long-term outcome and early neurological deterioration after ICH. Fifty healthy controls and 89 patients with acute spontaneous basal ganglia hemorrhage were recruited in this study. Plasma copeptin concentrations on admission measured by enzyme-linked immunosorbent assay were considerably high in patients than healthy controls. A multivariate analysis identified plasma copeptin level as an independent predictor for 1-year mortality, 1-year unfavorable outcome (modified Rankin Scale score>2) and early neurological deterioration. A receiver operating characteristic curve showed that the predictive value of plasma copeptin concentration was similar to that of National Institutes of Health Stroke Scale scores for long-term poor outcome and early neurological deterioration. However, copeptin did not obviously improve the predictive values of National Institutes of Health Stroke Scale scores. Thus, increased plasma copeptin level is an independent prognostic marker of 1-year mortality, 1-year unfavorable outcome and early neurological deterioration after ICH.

Plasma Copeptin in Preterm Infants - a Highly Sensitive Marker of Fetal and Neonatal Stress

Background: Copeptin is a stable by-product of arginine-vasopressin (AVP) synthesis and reflects its secretion by the pituitary. We investigated perinatal factors affecting copeptin concentrations in preterm infants at birth and at 3 days of life. Methods: A prospective cross-sectional study at two Swiss university hospitals was performed. 167 preterm infants were enrolled, 59 infants born between 24 and 31 weeks gestational age, 50 infants between 32 and 34 weeks, and 58 between 35 and 36 weeks. Plasma copeptin concentrations were determined by a CT-proAVP-Luminescence-immunoassay in umbilical cord blood at birth and in blood samples obtained at 2-3 days of life. Results: Copeptin at birth was significantly higher in preterm infants born vaginally (median [range] 366 [1-2900] pmol/L, n=43) than those born by caesarean section (6.9 [2-1580], n=124). In infants born after caesarean without prior labour (n=66), small for gestational age (< 5th percentile), suspect fetal heart rate, compromised placental perfusion, and chorioamnionitis were each associated with significantly elevated cord copeptin. Copeptin at 3 days of life was not associated with cord blood copeptin but inversely related to gestational age (Rs -0.6, p< 0.001) and birth weight (Rs -0.612, p< 0.001). Day 3 copeptin increased alongside the level of mechanical respiratory support. Conclusion: Copeptin is a highly sensitive marker of fetal and neonatal stress.

Correlation of Plasma Copeptin and Vasopressin Concentrations in Hypo-, Iso-, and Hyperosmolar States

Copeptin, the C-terminal moiety of provasopressin, is cosecreted with vasopressin. Copeptin may be a useful parameter to characterize disorders of water homeostasis and can be readily measured in plasma or serum. However, it is unknown to date how circulating copeptin and vasopressin levels correlate at different plasma osmolalites. To correlate plasma copeptin with plasma osmolality and vasopressin concentrations in healthy subjects during iso-, hypo-, and hyperosmolar states. Plasma osmolalities, copeptin, and vasopressin levels were measured in 20 volunteers at baseline, after an oral water load, and during and after iv infusion of 3% saline. Correlation coefficients were determined between plasma osmolalites and copeptin and vasopressin concentrations, as well as between vasopressin and copeptin concentrations. Median plasma osmolalities decreased from 290 mOsm/kg (range, 284-302) at baseline to 281 (273-288) mOsm/kg after water load and rose to 301 (298-307) mOsm/kg after hypertonic saline. Median plasma copeptin concentrations decreased from 3.3 (1.1-36.4) pm at baseline to 2.0 (0.9-10.4) pm after water load and increased to 13.6 (3.7-43.3) pm after hypertonic saline. Vasopressin and copeptin concentrations correlated with plasma osmolality (Spearman's rank correlation coefficient 0.49 and 0.77, respectively). There was a close correlation of vasopressin and copeptin concentrations (Spearman's rank correlation coefficient 0.8). Plasma vasopressin and copeptin correlate strongly over a wide range of osmolalities in healthy individuals. Therefore, the measurement of copeptin, which remains stable for several days, is a useful alternative to vasopressin measurements and will likely facilitate the differential diagnosis of disorders of water metabolism.

Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure

Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. All-cause mortality and cardiovascular mortality. After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P = .01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; P < .001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P = .048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; P < .001). Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.

Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration

IntroductionPost cardiac surgery vasodilatation (PCSV) is possibly related to a vasopressin deficiency that could relate to chronic stimulation of adeno-hypophysis. To assess vasopressin system activation, a perioperative course of copeptin and vasopressin plasma concentrations were studied in consecutive patients operated on for cardiac surgery.MethodsSixty-four consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass were studied. Hemodynamic, laboratory and clinical data were recorded before and during cardiopulmonary bypass, and at the eighth postoperative hour (H8). At the same time, blood was withdrawn to determine plasma concentrations of arginine vasopressin (AVP, radioimmunoassay) and copeptin (immunoluminometric assay). PCSV was defined as mean arterial blood pressure < 60 mmHg with cardiac index ≥ 2.2 l/min/m2, and was treated with norepinephrine to restore mean blood pressure > 60 mmHg. Patients with PCSV were compared with the other patients (controls). Student's t test, Fisher's exact test, or nonparametric tests (Mann-Whitney, Wilcoxon) were used when appropriate. Correlation between AVP and copeptin was evaluated and receiver-operator characteristic analysis assessed the utility of preoperative copeptin to distinguish between controls and PCSV patients.ResultsPatients who experienced PCSV had significantly higher copeptin plasma concentration before cardiopulmonary bypass (P < 0.001) but lower AVP concentrations at H8 (P < 0.01) than controls. PCSV patients had preoperative hyponatremia and decreased left ventricle ejection fraction, and experienced more complex surgery (redo). The area under the receiver-operator characteristic curve of preoperative copeptin concentration was 0.86 ± 0.04 (95% confidence interval = 0.78 to 0.94; P < 0.001). The best predictive value for preoperative copeptin plasma concentration was 9.43 pmol/l with a sensitivity of 90% and a specificity of 77%.ConclusionsHigh preoperative copeptin plasma concentration is predictive of PSCV and suggests an activation of the AVP system before surgery that may facilitate depletion of endogenous AVP stores and a relative AVP deficit after surgery.

High plasma mid-regional pro-adrenomedullin levels in children with severe dengue virus infections

Background Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is characterized by hemorrhage, plasma leakage and shock. Adrenomedullin and vasopressin are vaso-active hormones that mediate endothelial permeability, vascular tone and water balance and may therefore play a role during DHF/DSS. Adrenomedullin reduces endothelial permeability and has vasodilatory properties, while vasopressin is a potent vasoconstrictor with anti-diuretic effects. Objectives To determine mid-regional pro-adrenomedullin (MR-proADM) and copeptin, which are reliable and stable markers for adrenomedullin and vasopressin response, respectively, and relate their plasma concentrations to outcome and markers of plasma leakage in Indonesian children with DHF and DSS. Study design In this observational cohort study Indonesian children with DHF/DSS were enrolled. On study days 0 and 2, plasma MR-proADM and copeptin concentrations as well as parameters of plasma leakage were determined. Plasma MR-proADM and copeptin concentrations were compared to values of healthy controls. Results MR-proADM was increased in both DHF ( n = 43) and DSS ( n = 28) vs. controls ( n = 17), with median (IQR) values of 0.47 (0.40–0.68), 0.56 (0.44–1.00) vs. 0.22 (0.19–0.29) nmol/L, respectively. Additionally, MR-proADM correlated with signs of increased vascular leakage such as low albumin and increased pleural effusion. Copeptin concentrations showed no significant changes as compared to controls. Conclusions MR-proADM concentrations are elevated in children with DHF and DSS and correlate with the severity of plasma leakage, in contrast to copeptin concentrations. We speculate that adrenomedullin has a functional role in limiting endothelial hyperpermeability during DHF/DSS. Finally, MR-proADM may be a candidate biomarker to predict development of DHF/DSS.

The vasopressin and copeptin response to infection, severe sepsis, and septic shock*

To compare the course of arginine vasopressin (AVP) and copeptin plasma concentrations between patients with infection, severe sepsis, and septic shock. Prospective, closed-cohort study. Twelve-bed general and surgical intensive care unit and 33-bed internal medicine ward in a university hospital. Ten patients with infection, 22 with severe sepsis, and 28 with septic shock. None. Hemodynamic, laboratory and clinical data were recorded daily during the first 7 days after intensive care unit or hospital admission. Parallel thereto, blood was withdrawn to determine plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations. Standard tests, a mixed effects model, and a linear regression analysis were used for statistical analysis. The AVP response was different between the three study groups (p < 0.001) but did not change over time (p = 0.12). Although patients with severe sepsis and septic shock had higher AVP levels than did patients with infection (both p < 0.001), no difference in AVP concentrations was seen between severe sepsis and septic shock patients (p = 0.98). No difference in AVP was observed between survivors and nonsurvivors at day 28 (p = 0.87). In patients with severe sepsis, serum osmolarity (p < 0.001), arterial pH (p = 0.001), lactate (p < 0.001), and Pao2 (p = 0.04) were associated with the course of AVP plasma levels, whereas it was serum osmolarity alone in patients with septic shock (p = 0.03). Plasma AVP concentrations correlated with copeptin (r = .614, p < 0.001), but this correlation was influenced by continuous veno-venous hemofiltration (p = 0.002). Severe sepsis induced a stronger AVP response than infection without systemic inflammation. However, the lack of a difference in AVP plasma concentrations between patients with and without shock indicates that the AVP system does not function normally in severe sepsis. Our data support the hypothesis that impaired AVP response is at least partially responsible for the failure to restore vascular tone in septic shock.

POSTOPERATIVE VASOPRESSIN AND COPEPTIN LEVELS IN NONCARDIAC SURGERY PATIENTS

Further information on the endogenous arginine vasopressin (AVP) response in patients with postoperative systemic inflammatory response syndrome (SIRS) and vasodilatory shock would provide more insight into the pathophysiology of SIRS-associated cardiovascular failure and help indicate AVP therapy. Patients after uncomplicated abdominal surgery without SIRS (n = 10), critically ill patients after noncardiac surgery with SIRS (n = 9), and patients with SIRS plus vasodilatory shock (n = 22) were included in this prospective trial. Plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations together with clinical parameters were documented daily during the first 7 days postoperative. The AVP response significantly differed between the three groups. Patients without SIRS had lower AVP concentrations than SIRS patients with (P = 0.001) or without shock (P = 0.003). Patients with SIRS and shock had higher AVP levels than patients with SIRS alone (P < 0.001). Arginine vasopressin decreased over time (P = 0.007) in all groups. At day 28, nonsurvivors had higher AVP levels than did survivors (P < 0.001). In SIRS patients without shock, serum osmolarity was indirectly associated with AVP levels, whereas mean arterial blood pressure and serum osmolarity were associated with AVP in SIRS patients with shock. Arginine vasopressin and copeptin correlated significantly with each other (P < 0.001; r = 0.76). In patients without hemofiltration, copeptin levels predicted 28-day mortality with high sensitivity and specificity. The postoperative AVP response in noncardiac surgery patients seems well maintained. The possibility that AVP plays a contributory role in the failure to restore vascular tone in patients with vasodilatory shock cannot be excluded but seems less important than in septic or postcardiotomy shock.

Copeptin in the Differential Diagnosis of Hyponatremia

Treatment of patients with hyponatremia varies widely; thus, convenient diagnostic parameters are needed to guide the correct treatment strategy. This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia. In this prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing the syndrome of inappropriate antidiuresis (SIAD). Four patients (4%) were diagnosed as primary polydipsia, nine (8%) as diuretic-induced hyponatremia, 42 (40%) as SIAD, 29 (27%) as hypovolemic hyponatremia, and 22 patients (21%) as hypervolemic hyponatremia. In controls, a close correlation between plasma copeptin and serum sodium (r(2) = 0.62, P < 0.001) or urine osmolality (r(2) = 0.39, P = 0.001) was observed. Plasma copeptin levels were significantly higher in patients with hypo- and hypervolemic hyponatremia compared with SIAD (P < 0.005, respectively) and primary polydipsia (P < 0.001). The copeptin to U-Na ratio differentiated accurately between volume-depleted and normovolemic disorders (area under the receiver-operating characteristic curve 0.88, 95% confidence interval 0.81-0.95; P < 0.001), resulting in a sensitivity and specificity of 85 and 87% if a cutoff value of 30 pmol/mmol was used. The combined information of plasma copeptin less than 3 pmol/liter and urine osmolality less than 200 mOsm/kg ensured primary polydipsia in 100% of suspected patients. Copeptin measurement reliably identifies patients with primary polydipsia but has limited utility in the differential diagnosis of other hyponatremic disorders. In contrast, the copeptin to U-Na ratio is superior to the reference standard in discriminating volume-depleted from normovolemic hyponatremic disorders.

Copeptin in the differential diagnosis of hyponatremia

Background: Treatment of patients with hyponatremia varies widely; thus, convenient diagnostic parameters are needed to guide the correct treatment strategy. This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia. Methods: In this prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing the syndrome of inappropriate antidiuresis (SIAD). Results: Four patients (4%) were diagnosed as primary polydipsia, nine (8%) as diuretic-induced hyponatremia, 42 (40%) as SIAD, 29 (27%) as hypovolemic hyponatremia, and 22 patients (21%) as hypervolemic hyponatremia. In controls, a close correlation between plasma copeptin and serum sodium (r2 = 0.62, P < 0...

The vasopressin and copeptin response in patients with vasodilatory shock after cardiac surgery: a prospective, controlled study

To evaluate arginine vasopressin (AVP) and copeptin plasma concentrations in patients with vasodilatory shock after cardiac surgery. Prospective, controlled, clinical study. Surgical intensive care unit and cardiac surgery ward in a tertiary university teaching hospital. Thirty-three critically ill patients with vasodilatory shock after cardiac surgery and ten control patients undergoing uncomplicated aorto-coronary bypass surgery. Hemodynamic, laboratory and clinical data were recorded daily in all patients during the first 7 days after cardiac surgery. At the same time, points blood was withdrawn to determine plasma concentrations of AVP (radioimmunoassay) and copeptin (immunoluminometric assy). Standard tests, a mixed effects model and regression analyses were used for statistical analysis. The course of AVP was significantly different between groups (P < 0.001). While AVP concentrations were lower in the study group on the first postoperative day, they were higher than that in the control group from postoperative day 3 on. There was no difference in the postoperative AVP response between study patients with or without chronic angiotensin-converting enzyme inhibitor therapy. Except during continuous veno-venous hemofiltration, AVP and copeptin correlated significantly with each other (P < 0.001; r = 0.749). The AVP response to cardiac surgery is significantly different between patients with vasodilatory shock and patients undergoing uncomplicated aorto-coronary bypass surgery. Although no causative relationship between AVP concentrations and cardiovascular instability can be drawn from these results, our data support the hypothesis that inadequately low AVP plasma levels contribute to the failure to restore vascular tone in vasodilatory shock after cardiac surgery.

COPEPTIN, A STABLE PEPTIDE OF THE ARGININE VASOPRESSIN PRECURSOR, IS ELEVATED IN HEMORRHAGIC AND SEPTIC SHOCK

Arginine vasopressin (AVP) levels are increased in hemorrhagic and septic shock. Measurement of AVP levels has limitations due to its short half-life and cumbersome detection method. Copeptin is a more stable peptide derived from the same precursor molecule. We evaluated the plasma copeptin concentration in two independent studies: first, in an experimental baboon model of hemorrhagic shock, and second, in a prospective observational study of 101 consecutive critically ill patients at a university hospital. Copeptin was measured with a newly developed sandwich immunoassay using two polyclonal antibodies to the C-terminal region (amino acid sequence 132-164) of pre-pro-AVP. Copeptin concentrations in hemorrhagic shock increased markedly from median (range) of 7.5 [2.7-13) to 269 pM (241-456 pM). After reperfusion, copeptin levels dropped within hours to a plateau of 27 pM (15-78 pM). In the critically ill patient cohort, copeptin values increased significantly with the severity of the disease and were in patients without sepsis [27.6 pM [2.3-297 pM]), in sepsis [50.0 pM [8.5-268 pM]), in severe sepsis [73.6 pM [15.3-317 pM]), and in septic shock [171.5 pM (35.1-504 pM] compared with 4.1 pM (1.0-13.8 pM) in healthy controls (P for all vs. controls <0.001). On admission, circulating copeptin levels were higher in nonsurvivors (171.5 pM, 46.5-504.0 pM) as compared with survivors (86.8 pM, 8.5-386.0 pM; P = 0.01). Copeptin levels correlated with basal cortisol levels (r = 0.42; P < 0.001) and osmolality (r = 0.42; P < 0.001). In a logistic regression model including other covariates besides copeptin (e.g., determinants of fluid status) on survival, serum copeptin levels were the only independent significant predictor of outcome (P = 0.03). Copeptin concentrations are elevated in hemorrhagic and septic shock. Copeptin was higher on admission in nonsurvivors as compared with survivors, suggesting copeptin as a prognostic marker in sepsis. The availability of a reliable assay for the measurement of AVP release can also prove useful for the assessment of fluid and osmosis status in various diseases.

Comparative Evaluation of B-Type Natriuretic Peptide, Mid-Regional Pro-A-type Natriuretic Peptide, Mid-Regional Pro-Adrenomedullin, and Copeptin to Predict 1-Year Mortality in Patients With Acute Destabilized Heart Failure

The aim of the present study was to evaluate the capability B-type natriuretic peptide (BNP) as a prognostic marker in patients with acute destabilized heart failure in comparison with mid-regional pro-A-type natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), and the C-terminal part of the arginine vasopressin prohormone (Copeptin). BNP, MR-proANP, MR-proADM, and Copeptin plasma concentrations were obtained in 137 patients with acute destabilized heart failure attending a tertiary care hospital. The end point was defined as all-cause mortality, and the study participants were followed for 365 days. Of the 137 patients enrolled, 41 died and 96 survived during follow-up. ROC curve analysis showed that the areas under curve for the prediction of 1-year mortality were similar for BNP (0.716; 95% CI 0.633-0.790), MR-proANP (0.725; 95% CI 0.642-0.798), MR-proADM (0.708; 95% CI 0.624-0.782), and Copeptin (0.688; 95% CI 0.603-0.764). Using tercile approaches, Kaplan-Meier curve analyses demonstrated that the predictive value of all four analytes for survival probability was comparable (log-rank test for trend, P < .001 for each). In multivariable Cox proportional-hazards regression analyses, increased BNP, MR-proANP, MR-proADM, and Copeptin plasma concentrations were the strongest predictors of mortality. BNP is considered an established prognostic marker for heart failure patients. The present study provides evidence that MR-proANP, MR-proADM, and Copeptin measurements might have similar predictive properties compared with BNP determinations for one-year all-cause mortality in acute destabilized heart failure.

Copeptin and Arginine Vasopressin Concentrations in Critically Ill Patients

Determination of arginine vasopressin (AVP) concentrations may be helpful to guide therapy in critically ill patients. A new assay analyzing copeptin, a stable peptide derived from the AVP precursor, has been introduced. Our objective was to determine plasma copeptin concentrations. We conducted a post hoc analysis of plasma samples and data from a prospective study. The setting was a 12-bed general and surgical intensive care unit (ICU) in a tertiary university teaching hospital. Our subjects were 70 healthy volunteers and 157 ICU patients with sepsis, with systemic inflammatory response syndrome (SIRS), and after cardiac surgery. There were no interventions. Copeptin plasma concentrations, demographic data, AVP plasma concentrations, and a multiple organ dysfunction syndrome score were documented 24 h after ICU admission. AVP (P < 0.001) and copeptin (P < 0.001) concentrations were significantly higher in ICU patients than in controls. Patients after cardiac surgery had higher AVP (P = 0.003) and copeptin (P = 0.003) concentrations than patients with sepsis or SIRS. Independent of critical illness, copeptin and AVP correlated highly significantly with each other. Critically ill patients with sepsis and SIRS exhibited a significantly higher ratio of copeptin/AVP plasma concentrations than patients after cardiac surgery (P = 0.012). The American Society of Anesthesiologists' classification (P = 0.046) and C-reactive protein concentrations (P = 0.006) were significantly correlated with the copeptin/AVP ratio. Plasma concentrations of copeptin and AVP in healthy volunteers and critically ill patients correlate significantly with each other. The ratio of copeptin/AVP plasma concentrations is increased in patients with sepsis and SIRS, suggesting that copeptin may overestimate AVP plasma concentrations in these patients.