Surrogate Marker For Arginine Vasopressin Research Articles

Postsurgical utility of copeptin for the prediction of postoperative arginine vasopressin deficiency.

Arginine vasopressin deficiency (AVD) following neurosurgical procedures for pituitary disorders is common and can delay discharge. Copeptin, a stable surrogate marker of arginine vasopressin, may predict postoperative AVD. The authors' aim was to assess the optimal postoperative sampling time and cut-point concentration of copeptin to predict the development of postsurgical AVD. Adults without preexisting AVD who were undergoing surgery for a pituitary lesion between February 2020 and April 2022 were eligible for study inclusion. Two samples were drawn from each patient postoperatively to assess the copeptin concentration using an immunofluorescent assay. Samples were denoted as "early" (within 6 hours of extubation) or "postoperative day 1" (POD1; within 10-30 hours of extubation). Patients were evaluated for the development of AVD. One hundred ninety-two patients (54.2% female) with a median age of 54.5 years (IQR 39.8-67.0 years) were included in the study. The median copeptin concentration at both time points was significantly lower in those with AVD (transient or permanent; n = 22, 11.5%) than in those without (early: 4.9 vs 18.7 pmol/L, p < 0.001; POD1: 3.4 vs 4.9 pmol/L, p < 0.001) but did not differ in those who developed transient versus permanent AVD. The optimal copeptin cut point for the prediction of AVD was < 8.5 pmol/L for early samples (sensitivity 0.70, specificity 0.80, positive predictive value [PPV] 0.29, negative predictive value [NPV] 0.96) and < 4.3 pmol/L for POD1 samples (sensitivity 0.82, specificity 0.63, PPV 0.22, NPV 0.96). In early samples, a copeptin cutoff of 22.9 pmol/L increased the sensitivity for the detection of AVD to 95% with an NPV of 99%. The proportion of patients who had AVD was higher (60.0% vs 8.8%, p < 0.001) and the copeptin concentration lower (early: 4.3 vs 17.0 pmol/L, p < 0.001; POD1: 2.7 vs 4.9 pmol/L, p < 0.001) among those who had undergone surgery for a craniopharyngeal duct pathology versus a pituitary adenoma. Although copeptin was lower in patients with persistent Cushing's disease than in those in remission, the difference did not reach statistical significance (early p = 0.11, POD1 p = 0.52). Furthermore, the copeptin concentration could not predict the development of syndrome of inappropriate secretion of antidiuretic hormone. Patients without AVD who had received stress dose steroids intraoperatively had lower median early copeptin (11.7 vs 19.1 pmol/L, p = 0.027). In early postoperative copeptin samples, the optimal copeptin cut point for AVD diagnosis was < 8.5 pmol/L, and a level > 22.9 pmol/L had predicative utility in excluding AVD. Caution should be used when interpreting copeptin results, as patients administered glucocorticoids intraoperatively without AVD had lower median copeptin concentrations.

Racial Disparities in Fluid Intake and Plasma Copeptin in Young Adults

INTRO: Underhydration, or habitual low water intake, is associated with increased plasma copeptin, a surrogate marker of arginine vasopressin. Importantly, plasma copeptin is associated with development of cardiovascular disease (CVD) and chronic kidney disease (CKD). Compared with White individuals, Black individuals are more likely to be underhydrated, to develop CVD and end-stage CKD, and exhibit higher plasma copeptin in middle-age and older adulthood. However, there is limited information on potential racial differences in plasma copeptin in young apparently healthy adults, which may have implications for incident CVD and CKD. Therefore, we sought to determine whether young Black adults reported lower fluid intake and exhibited higher plasma copeptin concentration when compared with young White adults. Methods: We analyzed pre-existing data from two registered clinical trials (NCTs 04576338 and 05132556). Participants (n=86, sex; 40F/46M, race; White n=48, Black n=38, age; 21±2 years, BMI; 25±4 kg/m2) completed a three-day food and fluid log and underwent a venous blood draw to measure plasma copeptin concentration (BRAHMS Copeptin proAVP KRYPTOR). Food and fluid records were analyzed using the Nutrition Data System for Research for % fluid from food or water. Separately, records were used to operationalize beverage intake into 8 categories (water, sugar-sweetened beverages (SSB), milk/non-dairy alternatives, 100% juice, non-caloric beverages, plain coffee or tea, milk/sugar added coffee or tea, and alcohol). Statistical analyses included Mann-Whitney U tests for fluid intake data and ANCOVA for plasma copeptin concentration (controlled for site). Plasma copeptin was log transformed. Additionally, we assessed relations between fluid intakes and plasma copeptin concentration using Spearman’s (ρ) correlations. We set α at ≤ 0.05. Results: Compared with White adults, Black adults consumed less total fluid (Black; 1981 ±1035 vs. White; 2780±1242mL), water, alcohol, and coffee/tea (plain and milk/sugar-added), but more juice (all p’s&lt;0.05). There were no differences in % fluid from food or water, milk/non-dairy alternatives, non-caloric beverages, or SSBs. Black individuals exhibited ~22% higher plasma copeptin concentration (Black; 5.5±2.8 vs. White; 4.5±2.8pmol/L, ANCOVA p=0.022). Irrespective of race, copeptin was negatively correlated with water intake (ρ=-0.230, p=0.034). CONCLUSION: Black young adults reported a significantly lower fluid intake and exhibited higher plasma copeptin concentration when compared with White young adults. Future studies should attempt to address racial disparities in hydration practices, which may attenuate racial differences in copeptin and corresponding health disparities. NIH-K01HL147998 (ATR), Auburn University Offce of Vice President for Research Support Program (ATR). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of Copeptin in Predicting Postoperative Hyponatremia and Hypernatremia in Patients Undergoing Endoscopic Pituitary Adenoma Surgery.

Arginine vasopressin (AVP) is an important hormone responsible for maintaining sodium homeostasis after pituitary surgery. The measurement of AVP levels is difficult because of its short half-life (t1/2). Copeptin is a preprohormone of AVP, and it is a more stable peptide, which can be used as surrogate marker for AVP. This study aims to assess the role of copeptin as a predictor of postoperative hyponatremia and hypernatremia in patients undergoing endoscopic pituitary adenoma surgery. This prospective study included 50 patients who underwent endoscopic pituitary adenoma surgery. Serum copeptin levels of these patients were assessed (1) preoperatively (C1), (2) at extubation (C2), and (3) postoperative day 4 (C3). Perioperative data regarding fluid and sodium balance were collected from patients. Statistical analysis was done using the above data. The copeptin values were assessed against the sodium disturbances. 100% of patients who developed transient diabetes insipidus had a relative decrease in C2 from C1 (P - .0002). 88% of patients who developed early hyponatremia had a relative increase in C2 as compared with C1 (P < .01). 75% of patients who developed delayed hyponatremia had a relative increase in C3 as compared with C1 (P = .003). A relative increase or decrease in early change in copeptin (C2-C1) can predict development of early hyponatremia or transient central diabetes insipidus, respectively. A relative increase in delayed change in copeptin (C3-C1) can predict development of delayed hyponatremia.

Paediatric perspectives in the diagnosis of polyuria-polydipsia syndrome.

The elucidation of the underlying cause of polyuria-polydipsia syndrome (PPS)is a challenging-especially in the differentiation of partial defects of arginine vasopressin (AVP)secretion or action from primary polydipsia. The water deprivation test has been utilized for many decades, and its application in the paediatric population has been applied using parameters predominantly established in adult cohorts. In more recent times, the development of automated commercial assays for copeptin, a surrogate marker for AVP, has represented a significant advancement in the diagnostic approach to PPS. Measurement of copeptin concentrations has major advantages and has essentially superseded measurement of AVP in diagnostic protocols for PPS. Additionally, stimulated-copeptin protocols utilizing hypertonic saline infusion, arginine, and glucagon have been investigated, and are promising. However, further studies are required in the population-incorporating the differences in physiological regulation of water homeostasis, and safety requirements-before there is widespread adoption into clinical practice.

THU114 Postsurgical Use Of Copeptin In The Prediction Of Postoperative Arginine Vasopressin Deficiency

Abstract Disclosure: D.Z. Erickson: None. D. Donegan: None. J. Van Gompel: None. J. Atkinson: None. M. Link: None. F. Meyer: None. M. Peris-Celda: None. G. Spears: None. J. Bornhorst: None. M. Hoplin: None. Dysnatremias are common after neurosurgical procedures. Depending on the cohort assessed, transient arginine vasopressin deficiency (AVD) following neurological procedures is seen in up to 46% of patients which can delay discharge. Copeptin (COPEP), a stable surrogate marker of arginine vasopressin, has demonstrated utility in the prediction of postoperative AVD, however COPEP cutoff and sample timing has varied. Aim: To assess the optimal sampling time and cut point concentration of COPEP to predict the development of post-surgical AVD. Method: Adults who had transsphenoidal surgery (TSS) for a sellar or suprasellar mass between February 2020 and April 2022 without pre-existing AVD were prospectively enrolled if agreeable. Two COPEP samples (immunofluorescent assay on B.R.A.H.M.S Kryptor Compact PLUS) included “early” sample 1-6 hours following extubation, and another post-op day 1 (POD1, 10-30 hours of extubation). Patients were assessed for the development of AVD; defined as new onset hypotonic (&amp;lt; 295 mmol/kg) polyuria (&amp;gt;50 ml/kg/d) without other causes. Patient demographics and tumor characteristics were collected. Results: 192 patients (median age 54.5 (39.8-67.0) years with 54.2% female) were included. Surgical indications included non-functioning pituitary adenoma (N=101), functioning pituitary adenoma (N= 78), disorders or the craniopharyngeal duct (N=10) and other (N=3). Median COPEP levels were associated with age, but not sex. Median COPEP levels were significantly lower at both time points in patients who developed AVD (N=20, 10.4%) vs those who did not, (early: 4.9 vs 18.7 pmol/L, P= &amp;lt;0.001; POD1: 3.35 vs 4.9 pmol/L, P=&amp;lt;0.001). Change in median COPEP level between the 2 sample times was lower in those who developed AVD -1.8 pmol/L vs who did not -12.6 pmol/L (P&amp;lt;0.001). ROC curve analysis of early COPEP indicated that a level &amp;gt;20.3 pmol/L had a negative predictive value (NPV) of 97% whereas POD1 level &amp;gt;6.7 pmolL had a NPV of 96%. In univariate logistic analysis, lower early COPEP was associated with higher risk of AVD (OR=0.34, CI 0.26 -0.62, p=0.008), with an optimal cut point of 8.5 pmol/L. A similar association was seen for POD1 COPEP (OR=0.19, CI 0.07- 0.53, p= 0.002), which had an optimal cut point of 4.3 pmol/L. In patients with disorders of the craniopharyngeal system vs those who had TSS for other reasons, AVD was more common (60% vs 9%, P&amp;lt;0.001) and median COPEP levels were lower at both time points. Those without AVD who received stress dose steroids intraoperatively had lower median early COPEP (11.7 vs 19.1 pmol/L, P=0.27). Conclusion: In early samples taken following extubation, the optimal COPEP cut point for AVD diagnosis was 8.5 pmol/L and a level of &amp;gt;20.3 pmol/L has predicative utility in excluding AVD. However, caution should be used in patients who are administered glucocorticoids intra-operatively as this was associated with a lower median COPEP level. Presentation: Thursday, June 15, 2023

The Role of Arginine-Vasopressin in Stroke and the Potential Use of Arginine-Vasopressin Type 1 Receptor Antagonists in Stroke Therapy: A Narrative Review.

Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.

Copeptin as a Diagnostic and Prognostic Biomarker in Cardiovascular Diseases.

Copeptin is the carboxyl-terminus of the arginine vasopressin (AVP) precursor peptide. The main physiological functions of AVP are fluid and osmotic balance, cardiovascular homeostasis, and regulation of endocrine stress response. Copeptin, which is released in an equimolar mode with AVP from the neurohypophysis, has emerged as a stable and simple-to-measure surrogate marker of AVP and has displayed enormous potential in clinical practice. Cardiovascular disease (CVD) is currently recognized as a primary threat to the health of the population worldwide, and thus, rapid and effective approaches to identify individuals that are at high risk of, or have already developed CVD are required. Copeptin is a diagnostic and prognostic biomarker in CVD, including the rapid rule-out of acute myocardial infarction (AMI), mortality prediction in heart failure (HF), and stroke. This review summarizes and discusses the value of copeptin in the diagnosis, discrimination, and prognosis of CVD (AMI, HF, and stroke), as well as the caveats and prospects for the application of this potential biomarker.

Copeptin as a novel biomarker of cardiometabolic syndrome.

Arginine vasopressin (AVP), which is also called antidiuretic hormone (ADH), is a neurohormone synthetized from a pre-pro-hormone precursor in the supraoptic and paraventricular nuclei of the hypothalamus in response to increased plasma osmolality and decreased blood volume. AVP exerts several effects by binding to three different receptors: V1aR, V1bR, and V2R. In recent years, it has been suggested that increased plasma concentration of AVP may play a causal role in the development of type 2 diabetes, the metabolic syndrome, renal dysfunction and cardiovascular disease by influencing glucose homeostasis and lipid metabolism through several possible mechanisms involving V1aR and V1bR. V1aR located in the liver is involved in hepatic glycogenolysis and gluconeogenesis. V1bR, found in the pituitary gland and pancreas, mediates secretion of adrenocorticotrophic hormone (ACTH), insulin, and glucagon. However, AVP's clinical use as a biomarker is limited due to its short half-life in plasma (16-20 minutes), small size, and poor stability, which make direct measurement difficult. Copeptin, the biologically inactive, stable, C-terminal part of pro-vasopressin, is co-secreted with AVP in equimolar amounts and thus is considered an adequate and clinically useful surrogate marker of AVP. The aim of this review is to assess the current state of knowledge about the potential role of copeptin as a novel biomarker of cardiometabolic syndrome on the basis of recent scientific literature published up to December 2020 and searches of the PubMed, Google Scholar, and Web of Science databases.

Copeptin (CTproAVP) - A Biomarker of a Circulatory Impairment in Liver Transplant Recipients? A Prospective, Observational Study

Copeptin, an easily measured and stable surrogate marker of arginine vasopressin, is a biomarker of a homeostasis disorder and a circulatory impairment in a wide spectrum of morbidities. The aim of this study was to evaluate the potential of copeptin as a biomarker of a circulatory impairment in patients undergoing liver transplantation (LT). This was a prospective, observational study. Blood samples were obtained from 38 patients undergoing LT. Serum copeptin level was measured by means of a sandwich immunoassay pre-, intra-, and postoperatively up to 21 days after the operation. The mean concentration of copeptin remained in the range of values slightly below 1000 pg/mL during the analyzed observation period and remained higher than the values observed in healthy individuals. Intraoperative and immediately postoperative copeptin levels did not correlate with hemodynamic parameters. There was also no correlation between preoperative copeptin levels (C1) and preoperative Model for End-Stage Liver Disease scores, serum creatinine levels, plasma transaminase levels, international normalized ratio, or hematocrit (Spearman ρ, P > .05). Preoperative copeptin levels are elevated in most LT recipients and remain elevated for 21 days after surgery. There was no correlation between the concentration of copeptin and the Model for End-Stage Liver Disease-Sodium score or the cause of a hepatic failure. It cannot be concluded that copeptin is a biomarker of a circulatory impairment in patients with transplanted liver in the perioperative period. The secretion of vasopressin, as measured by copeptin concentration during and after LT, requires further study.

Serum Copeptin Level and High-Sensitivity C-Reactive Protein in Centrally Obese Middle-Aged Male Subjects

Background and Aim: Copeptin, a surrogate marker of Arginine Vasopressin, has been recently used as stress related neuroendocrine marker. In addition, chronic psychosocial stress had an association with increased inflammatory cytokines. Moreover, obesity has been recognized as high inflammatory status. Thus, it has been generated an interest whether centrally obese with high copeptin level have higher inflammatory status comparing to those with low copeptin level or not. Methods: Eighty-seven centrally obese male subjects between 40-60 years were recruited for this study. Anthropometric measurements such as height, weight, BMI and waist circumference were measured. Blood sample was collected to measure copeptin and hsCRP. Results: 29 subjects (33.33%) had low copeptin level (&lt;5 pmol/L) and 58 subjects (66.67%) had high copeptin level (≥5 pmol/L). Median hs-CRP levels were 2.86 mg/L (IQR: 1.63-6.7) and 3.42 mg/L (IQR: 2.44-5.46) in obese with low copeptin level and obese with high copeptin level respectively. There was no significant difference in hs-CRP levels between these two study groups (p=0.7). Conclusion: In the study population of the present study, there was no correlation found between copeptin and inflammatory status.

Copeptin Kinetics and Its Relationship to Osmolality During Rehydration for Diabetic Ketoacidosis in Children.

Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). The objective of this work is to characterize kinetics of copeptin and osmolality, and their dynamic relationship during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA. A prospective, observational, multicenter study was conducted. Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours. Measurements included temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), and association between-subject variability (BSV) (coefficient of variation, CV%). Twenty-eight children (20 newly diagnosed T1D) aged 1 to 16 years were included. Copeptin decreased from 95 pmol/L (95% CI, 55-136 pmol/L) (CV%, 158%) to 9.7 pmol/L (95% CI, 8.1-11.4 pmol/L) (CV%, 31%) with a 50% recovery time (t1/2) of 7.1 hours (range, 5.1-11.5 hours) (114%). Serum osmolality decreased from 321 mOsm/kg (range, 315-327 mOsm/kg) (4%) to 294 mOsm/kg (range, 292-296 mOsm/kg) (1%) with a t1/2 of 4.3 hours (range, 3.0-5.6 hours) (64%). Copeptin levels doubled with each osmolality increase by 15 mOsm/kg (range, 10-21 mOsm/kg) (59%), from 9.8 pmol/L (range, 7.3-12.3 pmol/L) (48%) to 280 mOsm/kg. Copeptin kinetics differed between newly diagnosed and known T1D patients (P = .001), and less between mild vs moderate-severe DKA (P = .04). First, this study characterized for the first time copeptin kinetics and dynamics in the high hyperosmolar range in children with DKA. Second, it revealed significant differences in copeptin kinetics between newly diagnosed and known T1D patients that may be explained by changes at the osmoreceptor and renal AVP receptor level due to longstanding osmotic diuresis and DKA.

The role of IL-1 in the regulation of copeptin in patients with metabolic syndrome

Arginine vasopressin (AVP) was suggested to contribute to cardiovascular risk and type 2 diabetes in patients with metabolic syndrome. The proinflammatory cytokine interleukin (IL)-1 is able to induce AVP secretion and plays a causal role in cardiovascular mortality and type 2 diabetes. We investigated in two studies whether copeptin levels – the surrogate marker for AVP – are regulated by IL-1-mediated chronic inflammation in patients with metabolic syndrome. Study A was a prospective, interventional, single-arm study (2014–2016). Study B was a randomized, placebo-controlled, double-blind study (2016–2017). n = 73 (Study A) and n = 66 (Study B) adult patients with metabolic syndrome were treated with 100 mg anakinra or placebo (only in study B) twice daily for 1 day (study A) and 28 days (study B). Fasting blood samples were drawn at day 1, 7, and 28 of treatment for measurement of serum copeptin. Patients with chronic low-grade inflammation (C-reactive protein levels ≥2 mg/L) and BMI >35 kg/m2 had higher baseline copeptin levels (7.7 (IQR 4.9–11.9) vs 5.8 (IQR 3.9–9.3) pmol/L, Pinflamm = 0.009; 7.8 (IQR 5.4–11.7) vs 4.9 (IQR 3.7–9.8) pmol/L, PBMI = 0.008). Copeptin levels did not change either in the anakinra or in the placebo group and remained stable throughout the treatment (P = 0.44). Subgroup analyses did not reveal effect modifications. Therefore, we conclude that, although IL-1-mediated inflammation is associated with increased circulating copeptin levels, antagonizing IL-1 does not significantly alter copeptin levels in patients with metabolic syndrome.

Copeptin-based diagnosis of diabetes insipidus.

Polyuria-polydipsia syndrome consists of the three main entities: central or nephrogenic diabetes insipidus and primary polydipsia. Reliable distinction between these diagnoses is essential as treatment differs substantially, with the wrong treatment potentially leading to serious complications. Past diagnostic measures using the classical water deprivation test had several pitfalls and clinicians were often left with uncertainity concerning the diagnosis. With the establishment of copeptin, a stable and reliable surrogate marker for arginine vasopressin, diagnosis of the polyuria-polydipsia syndrome has been newly evaluated. Whereas unstimulated basal copeptin measurement reliably diagnoses nephrogenic diabetes insipidus, two new tests using stimulated copeptin cutoff levels showed a high diagnostic accuracy in differentiating central diabetes insipidus from primary polydipsia. For the hypertonic saline infusion test, osmotic stimulation via the induction of hypernatraemia is used. This makes the test highly reliable and superior to the classical water deprivation test, but also requires close supervision and the availability of rapid sodium measurements to guarantee the safety of the test. Alternatively, arginine infusion can be used to stimulate copeptin release, opening the doors for an even shorter and safer diagnostic test. The test protocols of the two tests are provided and a new copeptin-based diagnostic algorithm is proposed to reliably differentiate between the different entities. Furthermore, the role of copeptin as a predictive marker for the development of diabetes insipidus following surgical procedures in the sellar region is described.

Copeptin as a marker of outcome after cardiac arrest: a sub-study of the TTM trial

BackgroundArginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest.MethodsSerial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score.ResultsSix hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deterioration within 24 h, and 273 (39.6%) died within 30 days. Copeptin measured at 24 h was found to be independently associated with 30-day survival, hazard ratio 1.17 [1.06–1.28], p = 0.001; circulatory cause of death, odds ratio 1.03 [1.01–1.04], p = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02–1.08], p < 0.001. Copeptin at 24 h was correlated with eCvSOFA score with rho 0.19 [0.12–0.27], p < 0.001.ConclusionCopeptin is an independent marker of severity of the post cardiac arrest syndrome, partially related to circulatory failure.Trial registrationClinical Trials, NCT01020916. Registered November 26, 2009.

Association of Copeptin, a Surrogate Marker of Arginine Vasopressin, with Decreased Kidney Function in Sugarcane Workers in Guatemala

Background: Vasopressin is elevated in response to heat and dehydration and has been postulated to have a role in the chronic kidney disease of unknown origin being observed in Central America. The aims of this study were to examine whether the vasopressin pathway, as measured by copeptin, is associated with the presence of kidney dysfunction, and to examine whether higher fluid intake is associated with lower circulating copeptin and thereby preserves kidney health among sugarcane workers exposed to hot conditions. Methods: Utilizing a longitudinal study of 105 workers in Guatemala, we examined relationships between hydration indices, plasma copeptin concentrations, and kidney function markers at 3 times during the 6-month harvest. We also examined whether baseline copeptin concentrations increased the odds of developing an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Results: Copeptin concentrations were positively associated with serum creatinine (β 1.41, 95% CI 0.88–2.03) and negatively associated with eGFR (β –1.07, 95% CI –1.43 to –0.70). In addition, as workers improved their hydration (measured by increases in fluid balance), copeptin concentrations were reduced, and this reduction was associated with an improvement in kidney function. Conclusions: Results suggest that copeptin should be studied as a potential prognostic biomarker.

Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5

BackgroundVascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30–70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5.MethodsCopeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography.ResultsPatients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman’s rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC.ConclusionsHigh circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.

Osmotic stimulation of vasopressin acutely impairs glucose regulation: a counterbalanced, crossover trial

Epidemiological studies in humans show increased concentrations of copeptin, a surrogate marker of arginine vasopressin (AVP), to be associated with increased risk for type 2 diabetes. To examine the acute and independent effect of osmotically stimulated AVP, measured via the surrogate marker copeptin, on glucose regulation in healthy adults. Sixty subjects (30 females) participated in this crossover design study. On 2 trial days, separated by ≥7 d (males) or 1 menstrual cycle (females), subjects were infused for 120 min with either 0.9% NaCl [isotonic (ISO)] or 3.0% NaCl [hypertonic (HYPER)]. Postinfusion, a 240-min oral-glucose-tolerance test (OGTT; 75 g) was administered. During HYPER, plasma osmolality and copeptin increased (P<0.05) and remained elevated during the entire 6-h protocol, whereas renin-angiotensin-aldosterone system hormones were within the lower normal physiological range at the beginning of the protocol and declined following infusion. Fasting plasma glucose did not differ between trials (P>0.05) at baseline and during the 120 min of infusion. During the OGTT the incremental AUC for glucose from postinfusion baseline (positive integer) was greater during HYPER (401.5±190.5 mmol/L·min) compared with the ISO trial (354.0±205.8 mmol/L·min; P<0.05). The positive integer of the AUC for insulin during OGTT did not differ between trials (HYPER 55,850±36,488 pmol/L·min compared with ISO 57,205±31,119 pmol/L·min). Baseline values of serum glucagon were not different between the 2 trials; however, the AUC of glucagon during the OGTT was also significantly greater in HYPER (19,303±3939 ng/L·min) compared with the ISO trial (18,600±3755 ng/L·min; P<0.05). The present data indicate that acute osmotic stimulation of copeptin induced greater hyperglycemic responses during the oral glucose challenge, possibly due to greater glucagon concentrations.This study was registered at clinicaltrials.gov as NCT02761434.

Exercise upregulates copeptin levels which is not regulated by interleukin-1

ObjectiveStudies have suggested that arginine vasopressin (AVP) and its surrogate marker copeptin increase during exercise, independently of serum sodium and/or osmolality. In extreme cases, this can lead to runners-induced hyponatremia. Interleukin-1 (IL-1) increases during exercise and induces AVP in animal models. We here therefore investigate whether copeptin (a surrogate marker for AVP) increases upon exercise in young and healthy males, and whether this increase is regulated by IL-1.DesignIn a randomized, placebo-controlled, double-blind, crossover trial in 17 healthy male volunteers, the effect of the IL-1 receptor antagonist anakinra on exercise-induced copeptin was compared with placebo.MethodsParticipants exercised for one hour at 75% of VO2max and were not allowed to drink/eat 6 hours before and during the study. Participants received either 100 mg of anakinra or placebo 1h before exercise. Blood was drawn at certain time intervals.ResultsIn both groups, copeptin levels were induced by 2.5-fold upon exercise (p<0.001), from 4.5–10.6 pmol/l in the placebo, and 4.3–11.3 pmol/l in the anakinra group, (p = 0.38). One hour after exercise, copeptin levels dropped to 7.7 and 7.9 pmol/l in the placebo and anakinra group, respectively (p = 0.58). The increase of copeptin levels was not explained by sodium concentrations.ConclusionsExercise induces a continuous rise of plasma copeptin levels in healthy male volunteers independently of sodium levels and fluid intake. This increase is not regulated by the IL-1 pathway.

Association of copeptin, a surrogate marker for arginine vasopressin secretion, with insulin resistance: Influence of adolescence and psychological stress

In middle-aged and elderly individuals, circulating copeptin concentrations, a surrogate marker for arginine vasopressin (AVP) secretion, associates with insulin resistance (IR). Whether this association is present in adolescents and young adults is unclear. Because psychological stress associates with higher circulating copeptin concentrations and IR, it has been speculated that increased AVP secretion could be a link between psychological stress and IR. We measured plasma copeptin concentrations in 351 14–16-year-old adolescents and 617 20–28-year-old young adults from the Danish site of the European Youth Heart Study, a population-based cardiovascular risk factor study in adolescents and young adults. IR was determined by the homeostatic model assessment method. Among the young adults, we used symptoms of depression, evaluated by means of the Major Depression Inventory (MDI) scale, as a measure of psychological stress. We applied linear regressions to examine associations, expressed as unstandardized regression coefficients (B) with 95% confidence intervals (CIs), between variables of interest, stratified by age group and adjusting for age, sex and Tanner stages. Copeptin and IR were log-transformed. Among the young adults, copeptin associated with IR (B (95%CI) = 0.19 (0.11 to 0.27), P < 0.001). This association was not found among the adolescents (B=-0.01 (-0.12 to 0.09), P = 0.78). MDI score associated with IR (B = 0.010 (0.004 to 0.016), P < 0.001) and copeptin (B=0.010 (0.004 to 0.015); P<0.002) in the young adults. Adjusted for copeptin, the strength of the association between MDI score and IR somewhat diminished (to B=0.008). In conclusion, adolescence and psychological stress appear to influence the association between copeptin and IR.

OP03-6 - The prognostic value of perioperative copeptin levels in patients undergoing carotid surgery

Copeptin is a stable, sensitive surrogate marker for Arginine vasopressin (AVP) [1]. It has been shown to be useful as a prognostic marker in patients with acute diseases [2]. Preoperative B-type natriuretic peptides is a predictor of mortality and myocardial infarction in patients undergoing noncardiac surgery [3]. The aim of the study was to evaluate the serum concentrations of copeptin, and B-type natriuretic peptide (BNP), and 3-years mortality in a cohort of patients operated for carotid stenosis.