Copeptin Levels Research Articles

Role of copeptin as biomarker of volume overload in children with end-stage renal disease

BackgroundChildren who undergo dialysis may develop hypertension and cardiovascular morbidity as a result of fluid overload. The intravascular parameter is clinically relevant in children because it directly influences systemic blood pressure, cardiac output, and cardiovascular squeals. Optimum fluid management is still a chronic clinical challenge, despite recent advances in the care of children with end-stage renal disease (ESRD). The paraventricular and supraoptic nuclei of the hypothalamus emit arginine vasopressin (AVP), a nonapeptide. It is secreted into the bloodstream by the pituitary gland in response to both osmotic and nonosmotic stimuli. Copeptin and AVP are released at equimolar concentrations. The aim of the study is to determine if copeptin, a surrogate marker of AVP, may be used to predict unfavorable outcomes, including chronic volume overload and its impact on hypertension and cardiovascular diseases in children undergoing dialysis.ResultsA cross-sectional study including 65 children: The mean age of the investigated patients was 10.79 ± 2.857 years, with 53% being male. The patient group had significantly greater mean blood levels of AVP and copeptin compared to the control group (P value = 0.0001). 45% of patients experienced cardiac issues, specifically left ventricular hypertrophy. Hypertensive patients accounted for 57%. The mean blood levels of AVP and copeptin were considerably greater in individuals with cardiac problems and hypertension.ConclusionsHemodynamics have a significant influence on cardiac function and hypertension in children receiving hemodialysis. Copeptin is a more appropriate biomarker for evaluating the effects of AVP on hypertension and cardiac problems in children with ESRD.

Prognostic role of serum copeptin levels in adults with graded traumatic brain injury.

The efficacy of copeptin in patients with severe head injuries remains unclear. To investigate the role of serum copeptin levels in detecting intracranial injury, assessing trauma severity, and predicting outcomes in adults with graded traumatic brain injury (TBI). This prospective non-randomized controlled study enrolled 78 adults with isolated head trauma, as well as 59 age- and sex-matched controls. Baseline serum copeptin levels were measured in both groups. Patients were categorized by head trauma severity using Glasgow Coma Scale (GCS) scores (severe GCS 3-8, moderate GCS 9-13, mild GCS 14-15) and by the presence of intracerebral or extracerebral lesions on cranial computed tomography (CCT). Patients were also classified as survivors or non-survivors. Serum copeptin levels were compared among these. Mean serum copeptin levels were significantly higher in patients with graded TBI than in controls. Furthermore, patients with severe and moderate head trauma had significantly higher copeptin levels compared with patients exhibiting mild trauma. An optimal copeptin cutoff value of > 1147pg/mL was identified, indicating the presence of moderate or severe trauma in TBI patients. Patients with abnormal CCT findings had significantly higher mean serum copeptin levels compared with patients exhibiting normal CCT scans. Non-survivors also showed significantly higher serum copeptin levels compared with survivors. Serum copeptin levels rise after graded TBI and can distinguish between patients with and without intracranial or extracranial lesions evident on CCT. Copeptin levels also aid in identifying moderate or severe TBI and in predicting 28-day mortality.

6379 Clonidin does not stimulate copeptin release

Abstract Disclosure: G. Binder: None. K. Weber: None. A. Peter: None. R. Schweizer: None. Background: Copeptin is secreted in isomolar amounts along with arginine vasopressin peptide from the posterior pituitary. Its stability makes it a perfect candidate for a biomarker of AVP deficiency. In children, the infusion of arginine and bolus of insulin stimulate copeptin; the respective stimulation test could be an alternative to the water deprivation test. Here, we retrospectively studied the effect of clonidine on copeptin release. Design and patients: This is a monocentric retrospective analysis of donated residual serum samples from 42 children with suspected of GH deficiency who underwent clonidine stimulation between 2020 and 2023. Measurements: Copeptin was measured in baseline, 30-, 60-, 90- and 120-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. GH was measured using an in-house RIA calibrated against the WHO International Reference Preparation 98/574. Results: According to the test results (clonidine and arginine test), there were 20 patients with GHD and 16 without GHD. No patient had polyuria-polydipsia syndrome. Median age was 6.7 years (quartiles; 5.6-7.8), the median height was -2.92 SDS (-3.42- -2.34), and the median BMI was-0.29 SDS (-1,32 - +0,16). The median baseline level of copeptin was 5,6 pmol/l (3.4-9.6). Median copeptin mildly decreased to 4.5 pmol/l (3.0-10.0) after 30 min; this change was not significant (P=0.45). Thereafter, median values remained low at 4.6, 4.6 and 4.6 pmol/l (60, 90 and 120 min). There was no correlation between baseline copeptin levels and the diagnosis of GHD. Conclusion: The clonidine stimulation test does not stimulate copeptin release and is therefore not suitable for the assessment of AVP deficiency in children. Presentation: 6/2/2024

6616 Copeptin Use To Reduce Hospital Stay In A Complicated DI Case

Abstract Disclosure: S.S. Kowsika: None. H. Moran: None. Introduction: While there is literature describing the use of copeptin for the diagnosis of polyuria-polydipsia syndrome, its utilization remains very limited in many hospitals. We present a case where the patient, initially misdiagnosed with central diabetes insipidus (DI), was appropriately diagnosed with partial nephrogenic DI through the use of copeptin. Case: A 48-year old female with a history of cardiac arrest, anoxic brain injury and diabetes insidious (DI) presented to the emergency department with hypernatremia (Na 154 mmol/L). The patient had been initiated on desmopresin (DDAVP) at an outside facility prior to her current admission. Despite receiving high doses of DDAVP, her sodium levels remained elevated, prompting further investigation. DDAVP administration was discontinued. A water deprivation test was subsequently performed, followed by IV administration of 2 mcg of DDAVP, which resulted in an increase in urine osmolality from 191 to 331 mosm/kg, which was less than the expected 50% increase observed in central DI. Additionally, a baseline copeptin level was obtained and noted to be 31 pmol/L, confirming the diagnosis of partial nephrogenic DI. The patient was started on Amiloride, leading to normalization of sodium levels. Discussion: Many patients with polyuria-polydipsia syndrome are frequently misdiagnosed and receive incorrect treatment, potentially worsening their clinical condition. Copeptin (Carboxy-Terminal-Pro-vasopressin) is the C-terminal peptide of pro-vasopressin, co-secreted with arginine vasopressin (AVP). It has been proposed as a direct test for diagnosing polyuria-polydipsia syndrome. Baseline Copeptin testing without stimulation can accurately diagnose nephrogenic DI if elevated (>21.4, pmol/L). To differentiate between central DI and chronic polyuria, prior thirsting with hypertonic saline or glucagon stimulation is necessary, with stimulated copeptin <4.9 pmol/L diagnosing central DI. Despite its diagnostic potential, Copeptin is underutilized in many settings. In this case, using Copeptin to accurately diagnose our patient led to appropriate treatment and the resolution of hypernatremia. Presentation: 6/1/2024

6520 Stimulated Copeptin Measurement in the Evaluation of a Patient Presenting Hypernatremia and Adipsia

Abstract Disclosure: B.R. Assunção: None. M.M. Freire: None. M. De Castro: None. A.C. Moreira: None. P.C. Elias: None. Introduction: Hypernatremia (hyperNA) in patients submitted to neurosurgery involving the hypothalamic region prompts the diagnosis of vasopressin deficiency (AVP-D), typically accompanied by increased thirst, polydipsia and polyuria. Classic adipsic AVP-D is characterized by hypotonic polyuria and no thirst in response to hyperNA. Clinical Case: A 21 yo male patient, followed since he had a surgery for a pilocytic astrocytoma of the third ventricle at 12 yo, presented hyperNA (154 mEq/L) with mild dehydration. He denied increased thirst, polyuria or polydipsia. Further evaluation showed elevated plasma and urinary osmolalities (pOsm: 317 mOsm/Kg; uOsm: 878 mOsm/Kg). The patient was admitted for hydration and fluid balance. Oral water intake (2500-3000L/day) was prescribed. Serum sodium (Na+) decreased from 158 to 133 mEq/L within 72h, and no polyuria was detected at hyper or normonatremic states. A 3% saline infusion test (SIT) was performed with thirst visual scale and plasma copeptin (CP) assessment. Na+ rose from 139 to 150 mEq/L and pOsm from 295 to 321 mOsm/kg, with no rise in thirst scale (4,2 to 4,8 cm). Basal and maximal 3% SIT CP levels were 3.1 and 3.2 pmol/L, respectively, also displaying subnormal values. CP assessed under hypovolemic hyperNA (Na+: 158 mEq/L) was 4.1 pmol/L, suggesting that this patient might have an adispic disorder with subnormal thirst and AVP osmotic responses, explaining the lack of polyuria. Patient was treated with fixed daily fluid intake with a last follow-up Na+ of 141 mEq/L.Discussion: Adipsic AVP-D is characterized by hypotonic polyuria and no thirst in response to hyperNA. However, polyuria, a hallmark of clinical presentation, was not observed in the present case. Other adipsic disorders include upward resetting of the osmotic thresholds for both thirst and AVP release (Type A); sub-normal thirst and AVP responses to osmotic stimuli (Type B); and intact osmoregulation of AVP release with absent thirst response (Type D). The lack of polyuria even in normovolemic conditions and the subnormal thirst and CP responses to normovolemic hyperNA and dehydrate states suggest the present case to be a Type B adipsic disorder. In those patients, the secretion of small amounts of AVP in response to osmotic stimulation explains why they retain the ability to concentrate urine, limiting free water excretion. Treatment is based on a fixed fluid intake of around 2 liters per day. Conclusions: Adipsic AVP-D and other adipsic disorders are extremely rare, presenting a great challenge in the diagnosis and management. To our knowledge, this is the first description of CP assessment in a patient with hyperNA and adipsia. CP might be an important diagnostic approach to adipsic disorders. Presentation: 6/2/2024

Copeptin as an inflammatory marker in diagnosis and prognosis of neonatal sepsis

BackgroundCopeptin is an immediate biomarker of individual stress response; many life-threatening diseases are causing a high elevation of its concentration in plasma, such as myocardial infarction and cardiovascular shock. Moreover, copeptin is a promising marker in sepsis. We aimed to evaluate copeptin as a diagnostic and prognostic marker in neonatal sepsis for the early initiation of appropriate therapy and the prediction of mortality. A prospective case-control study involved 237 neonates (165 cases had neonatal sepsis, and 72 served as controls). Cases were admitted to the neonatal intensive care unit (NICU) and followed up for symptoms and signs of sepsis confirmed by laboratory data: complete blood count (CBC), c-reactive protein (CRP), and cultures. Serum copeptin level by the enzyme-linked immunosorbent assay (ELISA) was measured for all included neonates. We observed that the copeptin level was significantly higher in cases than control (3.51 ± 1.4, 1.61 ± 0.51 pmol/liter, respectively). The cut-off value of copeptin at which we can discriminate between cases and controls was above 2.065 pmol/liter. Among cases, copeptin was higher in early-onset sepsis (EOS) than late-onset sepsis (LOS) neonates, and there was a significant correlation between its level and all the following: age at admission, birth weight, gestational age, history of perinatal asphyxia, maternal chorioamnionitis, and premature rupture of membrane (PROM). Also, copeptin was strongly associated with CRP level and the poor prognosis of patients. Copeptin can predict the death of cases at a cut-off value above 2.995 pmol/liter.ConclusionSerum copeptin level can be used as a diagnostic and prognostic marker in neonatal sepsis.

A New Biomarker Copeptin in Determining Disease Severity in COVID-19.

Copeptin is released from the posterior pituitary gland into systemic circulation in response to various stimuli, including stress. We aimed to evaluate the role of copeptin in determining the severity of the disease in patients with COVID-19. The study was conducted prospectively in two centers between June 1, 2022, and October 1, 2022. Severe and mild-moderate COVID-19 patients were compared in terms of clinical, laboratory and imaging findings, and serum copeptin levels at hospitalization. A total of 90 patients were included in the study; 45 patients were in severe disease groups. Dyspnea, loss of appetite, and loss of smell were significantly more common in the severe disease group (p<0.001, p=0.025, and p<0.001, respectively). Among the tomography findings, the consolidation frequency was similar in both groups (p=0.259). C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), procalcitonin, troponin and copeptin levels were higher in the severe group (p<0.05); hemoglobin, total protein and vitamin D levels were lower (p=0.05). The area under the curve (AUC) values for severe disease were 0.643 for copeptin (p=0.019), 0.656 for CRP (p=0.011), 0.684 for procalcitonin (p=0.004), 0.657 for ferritin (p=0.01), 0.72 for D-dimer (p=0), 0.688 for troponin (p=0.002), and 0.672 for age (p=0.005). In our study, copeptin was identified as a new prognostic biomarker indicating the severity of the disease in patients with COVID-19.

A single-centre retrospective study looking at copeptin levels in children and young people who underwent water deprivation test

A single-centre retrospective study looking at copeptin levels in children and young people who underwent water deprivation test

Establishment and Clinical Application in Stroke of a Serum Copeptin Time-Resolved Fluorescence Immunoassay.

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using thewell-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

Copeptin associates with major adverse cardiovascular events in patients on maintenance hemodialysis

BackgroundEnd-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. ObjectiveThis study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. MethodsESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. ResultsAmong 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. ConclusionElevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Circadian copeptin and oxytocin profiles in anorexia nervosa: Exploring the interplay with neurohypophysis opioid tone.

Neurohypophysis (NH) function in eating disorders (ED) remains poorly elucidated. Studies on vasopressin and oxytocin display inconclusive findings regarding their levels and associations with psychological complications in ED. The profile of opioid tone, a crucial NH activity regulator, is also unknown. To characterise the circadian profile of NH hormones and NH opioid tone using positron emission tomography/MRI (PET/MRI) imaging in patients with ED compared to healthy controls. Twelve-point plasma circadian profiles of copeptin and oxytocin, alongside nutritional and psychological scores, were assessed in age-matched female participants: 13 patients with anorexia nervosa restrictive-type (ANR), 12 patients recovered from AN (ANrec), 14 patients with bulimia nervosa and 12 controls. Neurohypophysis PET/MRI [11C] diprenorphin binding potential (BPND) was evaluated in AN, ANrec and controls. Results revealed lower copeptin circadian levels in both ANR and ANrec compared to controls, with no oxytocin differences. Bulimia nervosa exhibited elevated copeptin and low oxytocin levels. [11C] diprenorphin pituitary binding was fully localised in NH. Anorexia nervosa restrictive-type displayed lower NH [11C] diprenorphin BPND (indicating higher opioid tone) and volume than controls. In ANR, copeptin inversely correlated with osmolarity. Neurohypophysis [11C] diprenorphin BPND did not correlated with copeptin or oxytocin. Copeptin demonstrated significant group differences, highlighting its potential diagnostic and prognostic value. Oxytocin levels exhibited conflicting results, questioning the reliability of peripheral blood assessment. Increased NH opioid tone in anorexia nervosa may influence the vasopressin or oxytocin release, suggesting potential therapeutic applications.

Association of Preoperative Copeptin Levels with Risk of All-Cause Mortality in a Prospective Cohort of Adult Cardiac Surgery Patients.

We aimed to investigate the association of preoperative copeptin, a new cardiovascular biomarker, with short- and long-term mortality in a cohort of adult patients undergoing cardiac surgery, including its potential as a prognostic marker for clinical outcome. Preoperative blood samples of the Bern Perioperative Biobank, a prospective cohort of adults undergoing cardiac surgery during 2019, were analyzed. The primary and secondary outcome measures were 30-day and 1-year all-cause mortality. Optimal copeptin thresholds were calculated with the Youden Index. Associations of copeptin levels with the two outcomes were examined with multivariable logistic regression models; their discriminatory capacity was assessed with the area under the receiver operating characteristic (AUROC). A total of 519 patients (78.4% male, median age 67 y (IQR: 60-73 y)) were included, with a median preoperative copeptin level of 7.6 pmol/L (IQR: 4.7-13.2 pmol/L). We identified an optimal threshold of 15.9 pmol/l (95%-CI: 7.7 to 46.5 pmol/L) for 30-day mortality and 15.9 pmol/L (95%-CI: 9.0 to 21.3 pmol/L) for 1-year all-cause mortality. Regression models featured an AUROC of 0.79 (95%-CI: 0.56 to 0.95) for adjusted log-transformed preoperative copeptin for 30-day mortality and an AUROC of 0.76 (95%-CI: 0.64 to 0.88) for 1-year mortality. In patients undergoing cardiac surgery, the baseline levels of copeptin emerged as a strong marker for 1-year all-cause death. Preoperative copeptin levels might possibly identify patients at risk for a complicated, long-term postoperative course, and therefore requiring a more rigorous postoperative observation and follow-up.

Copeptin's role in traumatic brain injury: The promising quest for a new biomarker

ObjectiveTraumatic brain injury (TBI) necessitates reliable biomarkers to improve patient care. This study explored copeptin as a potential biomarker in TBI and its relation to vasopressin (ADH) in such patients. MethodsA cross-sectional study was conducted on 50 TBI patients. Exclusion criteria included specific medical conditions and recent traumatic events. Copeptin and ADH testing were performed within 30 days post-trauma. Patient data, Glasgow Coma Scale (GCS) scores, imaging results, and the need for surgical intervention were obtained from medical charts. ResultsCopeptin levels negatively correlated with GCS scores (ρ = − 0.313, p = 0.027), indicating a potential association with trauma severity. Copeptin levels (mean: 3.22 pmol/L, median 2.027 pmol/L, SD = 3.15) tended to be lower than those found in the normal population, suggesting possible neuroendocrine dysfunction post-TBI. ADH levels (mean: 67.93 pmol/L, median 56.474 pmol/L SD = 47.67) were higher than the normal range and associated with the need for surgery (p = 0.048). Surprisingly, copeptin and ADH levels negatively correlated (r = − 0.491; p < 0.001), potentially due to differences in degradation processes and physiological variations in TBI patients. ConclusionCopeptin shows potential as a predictive biomarker for assessing TBI severity and predicting patient outcome. However, its complex relationship with ADH in TBI requires further investigation. Careful interpretation is needed due to potential variations in excretion dynamics and metabolism. Larger studies on TBI patient cohorts are essential to validate copeptin as a reliable biomarker and improve patient care in TBI.

Nonspecific stress biomarkers for mortality prediction in older emergency department patients presenting with falls: a prospective multicenter observational study.

Older patients presenting to the emergency department (ED) after falling are increasingly prevalent. Falls are associated with functional decline and death. Biomarkers predicting short-term mortality might facilitate decisions regarding resource allocation and disposition. D-dimer levels are used to rule out thromboembolic disease, while copeptin and adrenomedullin (MR-proADM) may be used as measures of the patient`s stress level. These nonspecific biomarkers were selected as potential predictors for mortality. Prospective, international, multicenter, cross-sectional observation was performed in two tertiary and two regional hospitals in Germany and Switzerland. Patients aged 65years or older presenting to the ED after a fall were enrolled. Demographic data, Activities of Daily Living (ADL), and D-dimers were collected upon presentation. Copeptin and MR-proADM levels were determined from frozen samples. Primary outcome was 30-day mortality; and secondary outcomes were mortality at 90, 180, and 365days. Five hundred and seventy-two patients were included. Median age was 83 [IQR 78, 89] years, 236 (67.7%) were female. Mortality overall was 3.1% (30d), 5.4% (90d), 7.5% (180d), and 13.8% (365d), respectively. Non-survivors were older, had a lower ADL index and higher levels of all three biomarkers. Elevated levels of MR-proADM and D-dimer were associated with higher risk of mortality. MR-proADM and D-dimer showed high sensitivity and low negative likelihood ratio regarding short-term mortality, whereas copeptin did not. D-dimer and MR-proADM levels might be useful as prognostic markers in older patients presenting to the ED after a fall, by identifying patients at low risk of short-term mortality. ClinicalTrials.gov Identifier: NCT02244983.

Evaluating Serum Copeptin as a Promising Biomarker for Predicting Acute Ischaemic Stroke Severity: A Hospital-Based Study on Strokes.

Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to prognosticating the severity in the acute phase of stroke as well as help with risk stratification. Copeptin, an inactive peptide that is produced in an equimolar ratio to arginine vasopressin and adequately mirrors an individual's stress response to acute illnesses like acute ischaemic stroke as evidenced by elevated or increasing levels is being explored in this study to determine its relationship with acute stroke severity and infarct size on admission. This is a cross-sectional study of 80 neuroimaging-confirmed acute ischaemic patients who presented within seven days of symptom onset and 80 control subjects. The ischaemic stroke cases had stroke severity and infarct volume determined on admission by the National Institute of Health Stroke Scale (NIHSS) and neuroimaging (brain CT/MRI). A baseline serum copeptin level was measured in the study subjects. Spearman correlation and Kruskal Wallis test were used to determine the relationship between serum copeptin level with admission NIHSS and infarct size respectively. The receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of copeptin to predict severity and outcome. The mean age of the study group was 61.3 ± 12.7 years with 55.0% males and 45.0% females. The serum level of copeptin was significantly higher in the stroke cases with a median of 28.6 pmol/L (interquartile range (IQR)- 15.4-31.6 pmol/L) versus 8.8 pmol/L (IQR- 3.2- 10.7 pmol/L) among the stroke-free controls (p= 0.001) at a statistically significant level. There was a weak correlation between copeptin and NIHSS calculated at admission to measure stroke severity (r- 0.02, p= 0.873). Patients with infarct sizes in the fourth quartile (infarct sizes greater than 18.78 cm3) had higher copeptin levels, though this was not statistically significant (H= 2.88; p= 0.410). Admission serum copeptin did not show a statistically significant prognostic value in predicting stroke severity and mortality in stroke patients who presented within seven days of symptomonset with an area under curve (AUC) of 0.51 (95% CI: 0.36-0.65; p= 0.982). In this study, copeptin was higher among the stroke cases compared with the stroke-free controls which suggests a significant prognostic value in risk stratification in the acute phase of stroke; however, this did not significantly correlate with stroke severity and thus warrants further study in this field to elucidate it's fascinating potential as a prognostic biomarker (especially in the acute period) as this may enable allocation of a better-focused therapy for stroke patients.

Investigation of serum copeptin levels in patients with congestive heart failure

Aims: Congestive heart failure (CHF) is characterized by symptoms and signs of volume overload and tissue perfusion insufficiency and accompanied by neurohormonal activation. Copeptin is a part of pre-pro-vasopressin and synthesized in equal molar amounts with vasopressin. We aimed to evaluate the sensitivity and specificity of copeptin in indicating the diagnostic value of CHF Methods: This retrospective study included a total of 80 patients including 40 with heart failure and 40 healthy individuals. The groups were compared in terms of demographic features, laboratory findings including copeptin levels. Results: There was no statistically significant difference between the groups in terms of gender (p&gt;0.05). Age, hypertension, diabetes mellitus, smoking were statistically significantly higher in the heart failure group compared to the control group (p&lt;0.05). In both groups, serum copeptin levels were higher in men than in women. Copeptin levels in the heart failure group were statistically significantly higher than in the control group (p&lt;0.05). In the heart failure group, there was a negative correlation between serum copeptin levels and age, gender, hypertension, smoking, HDL cholesterol, hematocrit, creatinine levels. Conclusion: Copeptin is a good indicator of the course of the disease in patients with heart failure.

Urinary hyaluronidase activity is closely related to vasopressinergic system following an oral water load in men: a potential role in blood pressure regulation and early stages of hypertension development.

Blood pressure (BP) regulation is a complex process involving several factors, among which water-sodium balance holds a prominent place. Arginin-vasopressin (AVP), a key player in water metabolism, has been evoked in hypertension development since the 1980s, but, to date, the matter is still controversial. Hyaluronic acid metabolism has been reported to be involved in renal water management, and AVP appears to increase hyaluronidase activity resulting in decreased high-molecular-weight hyaluronan content in the renal interstitium, facilitating water reabsorption in collecting ducts. Hence, our aim was to evaluate urinary hyaluronidase activity in response to an oral water load in hypertensive patients (HT, n=21) compared to normotensive subjects with (NT+, n=36) and without (NT-, n=29) a family history of hypertension, and to study its association with BP and AVP system activation, expressed by serum copeptin levels and urine Aquaporin 2 (AQP2)/creatinine ratio. Eighty-six Caucasian men were studied. Water load test consisted in oral administration of 15-20 ml of water/kg body weight over 40-45 min. BP, heart rate, serum copeptin, urine hyaluronidase activity and AQP2 were monitored for 4 hours. In response to water drinking, BP raised in all groups with a peak at 20-40 min. Baseline levels of serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio were similar among groups and all decreased after water load, reaching their nadir at 120min and then gradually recovering to baseline values. Significantly, a blunted reduction in serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio was observed in NT+ compared to NT- subjects. A strong positive correlation was also found between urinary hyaluronidase activity and AQP2/creatinine ratio, and, although limited to the NT- group, both parameters were positively associated with systolic BP. Our results demonstrate for the first time the existence in men of a close association between urinary hyaluronidase activity and vasopressinergic system and suggest that NT+ subjects have a reduced ability to respond to water loading possibly contributing to the blood volume expansion involved in early-stage hypertension. Considering these data, AVP could play a central role in BP regulation by affecting water metabolism through both hyaluronidase activity and AQP2 channel expression.

The Association between Echocardiographic Parameters of Heart Failure with Preserved Ejection Fraction and Fluid Status Biomarkers in Hemodialysis Patients

Overhydration and cardiac function abnormalities are common in hemodialysis patients. The association of N-terminal prohormone for brain natriuretic peptide (NT-proBNP) and other fluid status biomarkers with echocardiographic parameters of heart failure with preserved ejection fraction (HFpEF) is scarcely investigated in this population. A total of 100 separate measurements performed in 50 dialysis patients (29 male, aged 60 ± 17 years) in NYHA class II/II and preserved left ventricle ejection fraction were analyzed. Plasma levels of NT-proBNP, mid-regional prohormone for atrial natriuretic peptide (MR-proANP) and copeptin (CPP) were measured. The E/e’ ratio as an index of HFpEF and other echocardiographic parameters were calculated. An E/e’ ratio &gt;9 was associated with higher median right ventricular systolic pressure (RVSP) and LVMI values. Left atrium volume index (LAVI) as well as NT-proBNP and MR-proANP, but not CPP levels were significantly higher in this group. In a stepwise multivariate analysis, only CPP and IL-6 levels were found to be independently associated with the E/e’ ratio in the study group, whereas NT-proBNP and MR-proANP were associated only with left heart structure parameters and LVEF. Of the analyzed biomarkers, only the CPP level was found to be independently associated with the E/e’ ratio in maintenance hemodialysis patients.

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

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

Sodium-Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction.

We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.