Copeptin Levels Research Articles

Association of serum copeptin and urinary uromodulin with kidney function, blood pressure and albuminuria at 6 weeks post-partum in pre-eclampsia.

Preeclampsia (PE) is associated with subsequent higher risk of cardiovascular and kidney disease. Serum copeptin, as a proxy for vasopressin, and urinary uromodulin, were associated with PE physiopathology and kidney functional mass respectively. We describe concentrations of these proteins in the post-partum period and characterize their association with persistent hypertension (HTN) or albuminuria. Patients with PE and healthy controls with uncomplicated pregnancy were prospectively included at two teaching hospitals in Switzerland. Clinical parameters along with serum copeptin and urinary uromodulin were measured at 6 weeks post-partum. PE patients were further characterized based on presence of HTN (defined as either systolic BP (SBP) ≥140 mmHg or diastolic (BP) ≥90 mmHg) or albuminuria [defined as urinary albumin to creatinine ratio (ACR) ≥3 mg/mmol]. We included 226 patients with 35 controls, 120 (62.8%) PE with persistent HTN/albuminuria and 71 (37.1%) PE without persistent HTN/albuminuria. Median serum copeptin concentration was 4.27 (2.9-6.2) pmol/L without differences between study groups (p > 0.05). Higher copeptin levels were associated with higher SBP in controls (p = 0.039), but not in PE (p > 0.05). Median urinary uromodulin concentration was 17.5 (7.8-28.7) mg/g with lower levels in PE patients as compared to healthy controls (p < 0.001), but comparable levels between PE patients with or without HTN/albuminuria (p > 0.05). Higher uromodulin levels were associated with lower albuminuria in PE as well as control patients (p = 0.040). Serum copeptin levels at 6 weeks post-partum are similar between PE patients and healthy controls and cannot distinguish between PE with or without residual kidney damage. This would argue against a significant pathophysiological role of the vasopressin pathway in mediating organ damage in the post-partum period. On the opposite, post-partum urinary uromodulin levels are markedly lower in PE patients as compared to healthy controls, potentially reflecting an increased susceptibility to vascular and kidney damage that could associate with adverse long-term cardiovascular and kidney outcomes.

The possible role of the vasopressin system in hematopoiesis

Vasopressin is a pleiotropic hormone that controls body fluid homeostasis. Vasopressin has also been proposed to be involved in erythropoiesis, thrombocyte activity and inflammation. However, whether increasing vasopressin is associated with changes in hematopoietic markers is not known. To evaluate this gap of knowledge we measured the vasopressin marker copeptin and markers of erythropoiesis (erythrocyte count, hemoglobin (Hb), red blood cell distribution width (RDW), mean corpuscular volume (MCV), erythrocyte volume fraction (EVF)), leukocyte count (total count, lymphocytes, neutrophils) and thrombocyte count in 5312 participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS). The associations between increasing copeptin tertile and the hematopoietic markers were analyzed in multivariate linear regression analyses. We found that increasing copeptin tertile was significantly (p < 0.001) associated with increasing erythrocytes, RDW, EVF, Hb, leukocytes and neutrophils after adjustment for age, sex, current smoking, prevalent diabetes, hypertension, creatinine, body mass index and physical activity. Increasing copeptin tertile was, however, not associated with change in MCV, lymphocyte or thrombocyte count. In conclusion, we found that increasing copeptin levels are positively associated with markers of erythropoiesis and leukocyte count in the general population. These results warrant further research on possible mechanistic effects of vasopressin on hematopoiesis.

Zonulin and copeptin relation to some metabolic markers in school-aged obese children

BackgroundUsing Zonulin and Copeptin as potential obesity markers in children, hasn’t yet been focused.AimTo evaluate the association between serum levels of both Zonulin and Copeptin with the obesity markers, and to assess their role as metabolic disturbance predictors in obese children.MethodsA case-control study comprised 111 Egyptian children (45 males and 66 females); aged 6–10 years to avoid the effect of puberty (prepubertal). They were classified according to their body mass index (BMI) percentiles into: 72 obese (BMI ≥ 95th ), and 39 control ones (BMI > 15th - <85th ), based on the Egyptian Growth Charts for children and adolescents. Anthropometric parameters and blood pressure were measured, and body composition analysis, lipid profile, Zonulin, and Copeptin levels were assessed.ResultsThe obese group showed a significantly higher value of Copeptin and a lower value of Zonulin than the control one Also, the obese group showed significant negative correlations between Zonulin and both anthropometric obesity markers and body composition, whereas Copeptin showed significant positive ones. Moreover, significant positive correlations were found between Copeptin and both body weight and fat distribution. Insignificant correlations were observed between both serum Zonulin and Copeptin levels and blood pressure and lipid profile.ConclusionZonulin and Copeptin cannot be used as metabolic disturbance predictors, among Egyptian children, as they were insignificantly correlated with lipid profile or blood pressure.

Food intake, plasma copeptin and cardiovascular risk in patients with type 2 diabetes: A cross-sectional analysis

Background and aimIncreased consumption of ultra-processed foods has been linked to both mortality and cardiovascular risk. Copeptin levels may serve as potential risk markers for cardiovascular death and events. This cross-sectional analysis seeks to assess the potential correlation between the intake of ultra-processed foods and copeptin levels in outpatients diagnosed with type 2 diabetes, based on estimates of cardiovascular risk. Methods and resultsOutpatients underwent clinical and nutritional assessments. Dietary information was gathered using a validated quantitative food frequency questionnaire, and the consumption of all foods, beverages, and food products was assessed according to the NOVA food classification system. Fasting plasma-EDTA samples were collected and preserved at −80 °C. Plasma copeptin measurements were analyzed using an enzyme-linked immunosorbent assay based on the competition principle. Participants were categorized into two groups: high risk and very high risk, based on cardiovascular risk calculated by the HEARTS calculator. A total of 190 participants were included in the evaluation, with an average age of 60 ± 9 years, glycated hemoglobin of 8.4 ± 1.4%, and a diabetes duration of 11 (5–19) years. Patients at a very high cardiovascular risk exhibited higher plasma copeptin levels compared to those at high cardiovascular risk. Notably, 92.1% of patients reported consuming more than 10% of total energy intake from ultra-processed foods, although this proportion did not differ between the two groups. ConclusionThis patient sample reported elevated consumption of ultra-processed foods; nevertheless, the correlation between ultra-processed foods and plasma copeptin has not been substantiated.

Uremic xerosis among patients on maintenance hemodialysis: Prevalence and correlation with clinical and laboratory markers

Xerosis, characterized by dry skin, is a frequent manifestation in patients undergoing maintenance hemodialysis. Understanding the prevalence of xerosis in this population and exploring its associations with various clinical and laboratory parameters is crucial for comprehensive patient care. The present study aimed to estimate the prevalence of xerosis in patients undergoing maintenance hemodialysis and to investigate the association between xerosis and various clinical and laboratory parameters, with a specific focus on serum copeptin as a surrogate for antidiuretic hormone.&#x0D; Methods. This cross-sectional observational study was conducted at the Hemodialysis Clinic of the Basrah Nephrology and Transplantation Center from March 1, 2022, to September 1, 2022. The prevalence of xerosis and its correlation with clinical characteristics and serum copeptin status were analyzed.&#x0D; Results. The study findings indicate that among the 48 patients undergoing maintenance hemodialysis, with an average age of 59.8 ± 8.8 years, 60.4% presented with xerosis. Serum copeptin levels, measuring 3.8 ± 2 ng/mL, showed a significant association with diuretic usage and serum parathyroid hormone (PTH) (p &lt; 0.001 and p = 0.031, respectively). Notably, no correlations were observed with other demographic or laboratory parameters, despite the tendency of serum copeptin levels to be higher in females and patients with low serum albumin and PTH concentrations.&#x0D; Conclusions. In summary, xerosis was prevalent in 60.4% of patients undergoing maintenance hemodialysis and demonstrated a positive correlation with diuretic use and serum PTH levels.

Hyponatremia due to preserved non-osmotic arginine vasopressin secretion in adipsic diabetes insipidus: a case report with review of literature.

Adipsic diabetes insipidus (ADI) is characterized by central diabetes insipidus and an impaired thirst response to hyperosmolality, leading to hypernatremia. Hyponatremia observed in patients with ADI has been considered a complication of desmopressin therapy. Herein, we present a case of impaired thirst sensation and arginine vasopressin (AVP) secretion without desmopressin therapy, in which hyponatremia developed due to preserved non-osmotic AVP secretion. A 53-year-old woman with hypopituitarism, receiving hydrocortisone and levothyroxine, experienced hyponatremia three times over 5 months without desmopressin treatment. The first hyponatremic episode (120 mEq/L) was complicated by a urinary tract infection with a plasma AVP level of 33.8 pg/mL. Subsequent hyponatremia episodes occurred after administration of antipsychotic (124 mEq/L) and spontaneously (125 mEq/L) with unsuppressed plasma AVP levels (1.3 and 1.8 pg/mL, respectively). Hypertonic saline infusion did not affect AVP or copeptin levels. Regulating water intake using a sliding scale based on body weight prevented the recurrence of hyponatremia without the use of desmopressin. Except during infection, plasma AVP levels (1.3 ± 0.4 pg/mL) were not significantly correlated with serum sodium levels (rs = -0.04, p = 0.85). In conclusion, we present a unique case of impaired thirst sensation and AVP secretion in which hyponatremia developed without desmopressin therapy. Preserved non-osmotic AVP secretion, possibly stimulated by glucocorticoid deficiency, may contribute to the development of hyponatremia in patients with ADI.

The Role of Anxiety Scales and Serum Copeptin Levels in Determining the Preprocedure Anxiety Status of Patients Who Undergo Fiberoptic Bronchoscopy and Endobronchial Ultrasonography

Introduction. Fiberoptic bronchoscopy (FOB) and endobronchial ultrasonography (EBUS) are safe and frequently used minimally invasive procedures. However, the decision to undergo an interventional procedure causes anxiety development and negative consequences in the individual. Objective. To determine the role of the State‐Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), visual analog scale (VAS), and serum copeptin levels, their sensitivity, specificity, and the correlation between them in the anxiety levels of patients before undergoing FOB and EBUS. Method. A total of 219 patients who were scheduled to undergo FOB/EBUS were included in this prospective observational study. Demographic data were recorded. Patients’ anxiety levels before the procedure were evaluated using STAI‐SA, STAI‐TA, BAI, and VAS. Copeptin levels were measured before and after the procedure. Results. Patients were moderately anxious according to STAI‐SA, STAI‐TA, and VAS and were mildly anxious according to the BAI. Women and patients aged under 65 years were significantly more anxious. All scales were positively correlated. Serum copeptin levels before the procedure were 5.8 ± 4.8 and 4.3 ± 3.9 ng/mL afterwards, with a significant difference between them. The specificity and sensitivity of VAS were found to be the highest. Conclusion. All anxiety scales are correlated with each other, and we recommend VAS as a powerful alternative for determining anxiety levels in terms of easier understanding and implementation. Serum copeptin levels before the procedure were significantly higher than afterwards and may be used as a potential biomarker for preprocedural anxiety.

Copeptin and the syndrome of inappropriate antidiuresis (SIAD) after pituitary transsphenoidal surgery.

This study evaluates the predictive value of copeptin for syndrome of inappropriate antidiuresis (SIAD) postpituitary transsphenoidal surgery (TSS). Data from 133 consecutive patients undergoing TSS (November 2017-October 2022) at Oxford University Hospitals NHS trust are presented in this retrospective study. Logistic regression (LR) and receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic utility of copeptin. The Mann-Whitney U test was used to compare copeptin levels between the SIAD and no SIAD groups. Fourteen patients (10.8%) developed SIAD. Copeptin was available in 121, 53 and 87 patients for Days 1, 241 and 8 post-TSS, respectively. LR for Day 1 copeptin to predict SIAD gave an odds ratio (OR) of 1.0 (95%CI 42 0.84-1.20, p = .99), area under-ROC curve (AUC) was 0.49; Day 2 copeptin OR was 0.65 (95%CI 0.39-1.19, 43 p = .77), AUC was 0.57 LR for Day 1 sodium to predict SIAD gave an odds ratio (OR) of 1.0 (95%CI 0.85-1.21, p = .99), AUC was 0.50. In conclusion, our data provide no evidence for copeptin as a predictive marker for post-TSS SIAD.

Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. There is a need for biomarkers that can be used for the diagnosis of sepsis and the early identification of patients at high risk of death. In this study, we aimed to investigate the relationship between Mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), and copeptin in sepsis. A total of 28 sepsis, 32 septic shock, and 30 control patients were included in our prospective study. Patients' MR-proADM, PCT, and copeptin levels were recorded. Sequential organ failure assessment scores, length of hospital stay, and 30-day mortality were also recorded. These values were compared between the sepsis, septic shock, and control groups. The mean age of all participants was 64.04 ± 15.83 years. In the study, 37 (61.6%) patients were female and 23 (39.3%) were male. There was no statistically significant difference in gender/age between all patient groups and the control group (for all, p > 0.05). We found a significant difference between the survivors and nonsurvivors in terms of MR-proADM, PCT, and copeptin levels. There was a significant difference between the sepsis and septic shock groups in terms of MR-proADM and PCT. A significant correlation was found between the length of hospital stay and MR-proADM and copeptin. MR-proADM, PCT, and copeptin may be useful in the prognosis of sepsis and to predict the length of stay in hospital and mortality.

Serum Copeptin Level as a Predictor of One-Year Mortality after Acute Decompensated Heart Failure Hospitalization

Background: Acutely decompensated heart failure patients have variable clinical outcomes. Some predictors of mortality in acute heart failure as resting heart rate, blood pressure, Pro-BNP level, and others have been identified. This study addresses the question whether copeptin may add value in the one-year prognosis in this category of high-risk patients. Results: To assess the relationship of serum copeptin level with one year mortality, we evaluated serum copeptin at admission and after 72 hours in 106 consecutive patients hospitalized for acute decompensated heart failure between May 2021 and November 2021 in a tertiary care hospital. Twenty-four patients (23.3%) died during the one-year follow-up period. The mortality was significantly higher in patients with advancing age, male sex, smokers, NYHA class IV heart failure, lower ejection fractions, higher heart rate, higher burden of arrhythmic events, lower creatinine clearance, and higher levels of copeptin at baseline and at day 3. Copeptin level at day 1 with cutoff value of ˃25.4 pmol/l predicted mortality with sensitivity 87.5% and specificity 70.73% [hazard ratio (95% confidence interval): (0.725 - 0.898), P&lt;0.001], while copeptin level at day 3 with cutoff value ˃ 26.1 pmol/l predicted mortality with sensitivity 100% and specificity 73.17% [hazard ratio (95% confidence interval): (0.876 - 0.981), P&lt;0.001]. Finally, increase in copeptin level from bassline was independently associated with increased mortality. (p˂0.001). Conclusions: Elevated copeptin level at baseline and 72 hours post-admission is suggested to be a strong predictor of one year mortality in patients with acute decompensated heart failure.

The diagnostic role of arginine-stimulated copeptin in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in pediatric age.

In recent years, copeptin stimulation through arginine administration has been evaluated as a new potential tool in the differential diagnosis of polyuria-polydipsia syndrome (PPS) in adults; to date very few data, all retrospective, exist in pediatric age. The aim of this prospective study is to evaluate the diagnostic performance of the arginine-stimulation test for copeptin in a cohort of pediatric patients affected by PPS. All children (<18 years) referred to the Department of Pediatric Endocrinology of the Regina Margherita Children Hospital for polyuria-polydipsia in the period January 2021-June 2023 were enrolled. The Arginine-stimulation test for copeptin was performed in all patients presenting PPS after water deprivation test (WDT). Patients with polyuria-polydipsia were then classified as having primary polyuria (PP), complete and partial central diabetes insipidus (CDI), according to the standardized interpretation. Arginine-stimulation test for copeptin was also performed in a control cohort. A significant difference in arginine-stimulated copeptin values was observed at baseline (p = 0.005), at 60 min (p = 0.01), and at 90 min (p = 0.005) in 7 subjects presenting PP, 6 patients affected by CDI and 50 subjects of the control cohort. Plasma osmolality values remained stable at all measurements. The arginine-stimulated copeptin test demonstrated sensitivity and specificity of 100%, whereas the sensitivity of the WDT test was 83.3% and the specificity was 85.7%. Given the reliability and the minor adverse effects and costs, the copeptin level after arginine administration could replace the WDT in the diagnostic workup of these in pediatric age.

Fluid homeostatic action of dapagliflozin in patients with chronic kidney disease: the DAPA-BODY Trial.

Sodium glucose cotransporter 2 (SGLT2) inhibitors have both glucose-lowering and diuretic effects. We recently reported that the SGLT2 inhibitor dapagliflozin exerts short-term fluid homeostatic action in patients with chronic kidney disease (CKD). However, the long-term effects of SGLT2 inhibitors on body fluid status in patients with CKD remain unclear. This was a prospective, non-randomized, open-label study that included a dapagliflozin treatment group (n = 73) and a control group (n = 24) who were followed for 6 months. Body fluid volume was measured using a bioimpedance analysis device. The extracellular water-to-total body water ratio (ECW/TBW), a predictor of renal outcomes, was used as a parameter for body fluid status (fluid retention, 0.400 ≤ ECW/TBW). Six-month treatment with dapagliflozin significantly decreased ECW/TBW compared with the control group (-0.65% ± 2.03% vs. 0.97% ± 2.49%, p = 0.0018). Furthermore, dapagliflozin decreased the ECW/TBW in patients with baseline fluid retention, but not in patients without baseline fluid retention (-1.47% ± 1.93% vs. -0.01% ± 1.88%, p = 0.0017). Vasopressin surrogate marker copeptin levels were similar between the control and dapagliflozin groups at 6 months (32.3 ± 33.4 vs. 30.6 ± 30.1 pmol/L, p = 0.8227). However, dapagliflozin significantly increased the change in copeptin levels at 1 week (39.0% ± 41.6%, p = 0.0010), suggesting a compensatory increase in vasopressin secretion to prevent hypovolemia. Renin and aldosterone levels were similar between the control and dapagliflozin groups at 6 months, while epinephrine and norepinephrine (markers of sympathetic nervous system activity) were significantly lower in the dapagliflozin group than in the control group. In conclusion, the SGLT2 inhibitor dapagliflozin ameliorated fluid retention and maintained euvolemic fluid status in patients with CKD, suggesting that SGLT2 inhibitors exert sustained fluid homeostatic actions in patients with various fluid backgrounds. Clinical trial registration: https://www.umin.ac.jp/ctr/, identifier [UMIN000048568].

High level of psychological stress in COVID-19 recovered individuals: role of copeptin as a potential biomarker.

Study aimed to assess stress in COVID-19 recovered individuals using a validated questionnaire PSS-10 score and stress biomarkers - salivary cortisol and serum copeptin. A total of 83 subjects of which 54 subjects (66.3%) who were hospitalized were recruited 8-20 weeks following recovery from COVID-19. Stress was assessed by PSS-10 stress-scale after a mean duration of 14.5 weeks after recovery. Sixty-eight subjects (81.9%) had new or persistent symptoms after recovery. Subjects were divided into two groups on the basis of PSS score; mild stress (PSS:0-13) and moderate to severe stress (PSS:>14) and levels of biomarkers (serum copeptin, DHEAS and salivary cortisol) were compared in the two groups. Forty-four subjects (53%) had moderate to severe stress and 39 subjects (47%) had mild stress. Subjects with post COVID symptoms had significantly higher stress levels as compared to subjects who were asymptomatic [15 vs. 9; p = 0.003]. Serum copeptin levels were significantly higher among subjects with moderate to severe stress as compared to those with mild stress [0.41 vs. 0.67 ng/mL; p = 0.031]. Subjects with moderate to severe stress had higher median salivary cortisol compared to subjects with mild stress [1.03 vs. 1.44 nmol/L; p = 0.448]. Our study demonstrated moderate to severe stress in over half and some level of stress in nearly all COVID recovered individuals even after 3 months. Serum copeptin was found to be a useful biomarker to objectively measure stress in these subjects.

The association of copeptin with metabolic risk markers is modified by region of origin

Iraqi born immigrants in Sweden have higher prevalence of metabolic diseases compared to native Swedes. Copeptin, a marker for vasopressin, is associated with increased risk of metabolic disease. In this cross-sectional population study based on the MEDIM cohort we investigated differences in copeptin levels between Iraqi and Swedish born individuals and if the association between copeptin and cardiometabolic risk markers differed by region of origin. We included 1109 Iraqi and 613 Swedish born participants (58% men, mean age 47 years). The Swedish participants had a higher concentration of copeptin compared to the Iraqi born group after age and sex adjustment (p < 0.001). This difference existed only among male individuals with the highest copeptin concentrations, i.e. belonging to copeptin quartile 4 (median (25th; 75th percentile) 20.07 (15.27;33.28) pmol/L for the Swedish born versus 15.57 (13.91;19.00) pmol/L for the Iraqi born, p < 0.001). We found a significant interaction between copeptin (continuous ln-transformed) and being born in Iraq regarding the association with plasma triglycerides (Pinteraction = 0.006). The association between copeptin and BMI was stronger amongst the Iraqi born individuals compared to the Swedish born. Together, this could indicate that copeptin is a more potent marker of metabolic disease among individuals born in Iraq compared to Sweden.

The role of arginine vasopressin in the pathophysiology of microvascular dysfunction after ST-elevation myocardial infarction

Abstract Background Coronary microvascular dysfunction (CMD) after ST-elevation myocardial infarction (STEMI), in part due to impaired vasomotor tone, predicts heart failure and mortality at one year. Arginine vasopressin (AVP) may be implicated in CMD as it is released during MI and has known vasoconstrictor effects, but data in humans are lacking. We examined the role of copeptin, a stable plasma surrogate marker of AVP, in humans with STEMI. Methods We included three cohorts. The first cohort prospectively recruited patients presenting with STEMI eligible for primary percutaneous coronary intervention (PPCI) (n= 55). In this cohort, the index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured in the culprit artery at the end of the procedure. The second cohort included 45 patients from a sub-study of the CAPRI trial (Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary PCI; NCT02390674). In this cohort, patients underwent cardiac magnetic resonance (CMR) imaging at one and 12 weeks post-MI, allowing precise measurement of infarct size and microvascular obstruction (MVO), the imaging hallmark of CMD. Both cohorts had serum copeptin measured at four time points. The 3rd cohort included two patients undergoing trans-coronary alcohol ablation of septal hypertrophy (TASH). Serial copeptin measurements were performed in this cohort to assess copeptin release in an induced ischaemia setting. Results One hundred patients were included from both STEMI cohorts. Copeptin levels paralleled AVP plasma levels closely, with mean levels falling in the 24 hours after reperfusion from 92.5 pmol/L to 6.4 pmol/L, and this was mirrored in the TASH patients. Copeptin release wasinversely linked to admission diastolic blood pressure (DBP) (Spearman’s rho r= -0.431, p=0.001), but did not correlate with systolic blood pressure. Copeptin levels at 24 hours were significantly associated with high IMR (r=0.372, p=0.011) and low CFR (r=-0.467, p=0.001). Patients with IMR &amp;gt;40 also had significantly higher mean copeptin concentration at 24 hours than those with lower IMR (19.1 vs 7.1pmol/L, p=0.019, Figure 1). Finally, patients with MVO on early CMR showed a trend towards higher mean copeptin concentration at baseline, although this was not statistically significant. Notably, copeptin levels were not associated with infarct size on either early or late CMR. Conclusions Copeptin, and therefore AVP, is released secondary to acute myocardial ischaemia, particularly in response to reduced coronary perfusion, as evidenced by the inverse correlation with DBP, and normalises by 24 hours. However, evidence of CMD was seen in patients with persistently elevated copeptin at 24 hours, suggesting AVP may contribute to microcirculatory dysfunction. AVP receptor antagonists may represent a novel therapeutic option in patients with STEMI and evidence of microvascular dysfunction.

Serum Copeptin, Perceived Stress, and Pain in Patients Living with Sickle Cell Disease

Sickle cell disease (SCD) is a hereditary blood disorder characterized by intense acute and chronic pain episodes, resulting in a complex interplay of negative physical and emotional experiences. One of the main barriers to addressing pain in this disease state is the limited information about the mechanisms affecting the variable degree and types of pain and stress that impact patients in this population. The arginine vasopressin receptor1a gene (AVPR1A) single nucleotide polymorphism (rs10877969) is associated with aspects of acute pain and stress related pain in patients living with SCD. Arginine vasopressin (AVP) is a hormone known for its role in regulating extracellular fluid, vasoconstriction, and the endocrine stress response. However, due to its short half-life, AVP is difficult to measure. Thus, copeptin, the stable biologically inactive C-terminal portion of pro-vasopressin, is often used as a surrogate marker for AVP secretion. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activation, however, its levels have not been studied in patients living with SCD. Psychological stress has been associated with changes in circulating copeptin concentrations. Considering the relationship between pain, stress, and copeptin, it is important to investigate their relationship in the context of SCD. The primary objective of this study was to examine serum copeptin levels with reports of perceived stress and pain in this patient population. In this cross-sectional study, we investigated serum copeptin levels, perceived stress, and pain experiences in a cohort of 50 adults living with SCD. Th participants had a mean age of 39.8±8.5 years, ranging from 29 to 59 years. Ninety-six percent of the participants were of African ancestry and 62% were female. Participants had the following hemoglobin genotypes: 68% had SS, 24% had SC, and 8% had other Hgb genotypes. To assess pain experiences, participants responded to questionnaires, including the Average Pain Intensity (API, average of current, least, and worst pain experienced within a 24-hour period, measured on a scale from 0 to 10). The Adult Sickle Cell Quality of Life Measure (ASCQ-Me) was used to measure number of vaso-occlusive crises (VOC). Perceived stress was assessed using the Perceived Stress Scale (PSS). Serum copeptin levels were quantified using a well-established laboratory. All the participants provided blood samples and completed psychological scales. Descriptive statistics and bivariate associations were conducted using R statistical software package. The study received approval from the Institutional Review Board at the University of Tennessee Health Science Center. We observed no significant differences in mean copeptin levels by sex ( p=.33) or associations between copeptin levels and age ( p=.66), weight ( p=.81), number of hospitalizations due to pain crisis ( p=.23), and the number of pain crisis managed at home ( p=0.07). The coefficients for API .92 ( p=.05) and PSS .97 ( p=.03) exhibited statistically significant positive association with copeptin levels. Our findings provide insights into the relationship between serum copeptin levels, perceived stress, and pain intensity in patients with sickle cell disease (SCD). The positive associations observed between copeptin levels and both perceived stress and average pain intensity underscore the potential interchange of pain and psychological stress in the regulation of copeptin secretion in this patient population. Our results indicate that copeptin levels are not significantly influenced by sex, age, or weight suggesting that these demographic factors may not be major determinants of copeptin viability in patients living with SCD. While sickle cell severity indicators did not show significant associations with copeptin levels, further investigation with larger sample sizes is needed to validate these findings and explore additional factors contributing to pain and psychological stress in individuals living with SCD. Ultimately, understanding the complexities of copeptin regulation may lead to improved pain management strategies and enhanced overall well-being for patients with this challenging disorder.

Cancer and the Vasopressin Gene: Radioimmunoassay Values and Commentary on Copeptin as a Plasma Marker.

Vasopressin gene expression has been demonstrated to be a common feature of all small-cell lung cancer (SCLC) and breast cancer. Provasopressin (ProVP) is a component of the cancer cell membrane and a likely target for treatment. However, a measurable fraction of this cancer provasopressin is also normally processed and products are released into the circulation. Vasopressin (VP) and vasopressin-associated human neurophysin (VP-HNP), two of three products of processing, were earlier shown to be reliable plasma markers for determining the presence of SCLC and monitoring response to treatment. In this study, copeptin, the third product of provasopressin processing, was preliminarily evaluated as a plasma marker for SCLC or breast cancer using radioimmunoassay (RIA). Antibodies directed against the 18 residue C-terminal peptide fragment of copeptin were used to avoid interference from the large-carbohydrate component of this endogenous glycopeptide. The levels of copeptin in 8 male and 6 female patients with SCLC before treatment ranged from 16 to 319 pmol/L, and these levels were elevated (>2.5 times) in 10 of 14 cases (70%) when compared with healthy volunteers (normal mean, 18 ± 6 pmol/L). Volunteer values for males were smaller than for females (15± 4 pmol/L and 20± 9 pmol/L), but numbers were small. Patients with breast cancer had plasma levels ranging from 12 to 68 pmol/L, with only three of the six elevated. While cancer patients displayed a wide range of plasma copeptin levels over 70% with SCLC and 50% with breast cancer had clearly elevated levels. This finding indicates that for such patients, plasma copeptin, like plasma VP and VP-HNP, could be used to detect disease. The control values found for healthy volunteers using our RIA were in a range predictable from established normal plasma levels of both VP and VP-HNP.

DKK3 as a potential novel biomarker in patients with autosomal polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, and leads to a steady loss of kidney function in adulthood. The variable course of the disease makes it necessary to identify the patients with rapid disease progression who will benefit the most from targeted therapies and interventions. Currently, magnetic resonance imaging-based volumetry of the kidney is the most commonly used tool for this purpose. Biomarkers that can be easily and quantitatively determined, which allow a prediction of the loss of kidney function, have not yet been established in clinical practice. The glycoprotein Dickkopf 3 (DKK3) which is secreted in the renal tubular epithelium upon stress and contributes to tubulointerstitial fibrosis via the Wnt signaling pathway, was recently described as a biomarker for estimating risk of kidney function loss, but has not been investigated for ADPKD. This study aimed to obtain a first insight into whether DKK3 may indeed improve outcome prediction in ADPKD in the future. In 184 ADPKD patients from the AD(H)PKD registry and 47 healthy controls, the urinary DKK3 (uDKK3) levels were determined using ELISA. Multiple linear regression was used to examine the potential of these values in outcome prediction. ADPKD patients showed significantly higher uDKK3 values compared with the controls (mean 1970 ± 5287 vs 112±134.7 pg/mg creatinine). Furthermore, there was a steady increase in uDKK3 with an increase in the Mayo class (A/B 1262 ± 2315 vs class D/E 3104±7627 pg/mg creatinine), the best-established biomarker of progression in ADPKD. uDKK3 also correlated with estimated glomerular filtration rate (eGFR). Patients with PKD1 mutations show higher uDKK3 levels compared with PKD2 patients (PKD1: 2304±5119; PKD2: 506.6±526.8 pg/mg creatinine). Univariate linear regression showed uDKK3 as a significant predictor of future eGFR slope estimation. In multiple linear regression this effect was not significant in models also containing height-adjusted total kidney volume and/or eGFR. However, adding both copeptin levels and the interaction term between copeptin and uDKK3 to the model resulted in a significant predictive value of all these three variables and the highest R2 of all models examined (∼0.5). uDKK3 shows a clear correlation with the Mayo classification in patients with ADPKD. uDKK3 levels correlated with kidney function, which could indicate that uDKK3 also predicts a disproportionate loss of renal function in this collective. Interestingly, we found an interaction between copeptin and uDKK3 in our prediction models and the best model containing both variables and their interaction term resulted in a fairly good explanation of variance in eGFR slope compared with previous models. Considering the limited number of patients in these analyses, future studies will be required to confirm the results. Nonetheless, uDKK3 appears to be an attractive candidate to improve outcome prediction of ADPKD in the future.

OR20-06 Diagnosing Central Diabetes Insipidus Using Copeptin Upon Hypertonic Saline Versus Arginine Stimulation

Abstract Disclosure: J. Refardt: None. C. Atila: None. I.O. Chifu: None. E. Ferrante: None. Z. Erlic: None. J.B. Drummond: None. B. Mantovani: None. R. Drexhage: None. C.O. Sailer: None. A. Widmer: None. S. Felder: None. A.S. Powlson: None. N. Hutter: None. D. Vogt: None. M. Gurnell: None. B. Rocha: None. J. Hofland: None. F. Beuschlein: None. M. Fassnacht: None. B.F. Winzeler: None. M. Christ-Crain: None. Background: The main challenge in the diagnosis of central diabetes insipidus (cDI) is its distinction against primary polydipsia (PP). Hypertonic saline stimulated copeptin has a high diagnostic accuracy of 97%, but comprises discomfort for patients and requires close sodium monitoring. Arginine stimulated copeptin showed similar diagnostic accuracy of 93% with better tolerability, but a head-to-head comparison is lacking. We hypothesized that arginine stimulated copeptin is non-inferior (non-inferiority margin 10%) to hypertonic saline stimulated copeptin for the diagnosis of cDI. Methods: In this prospective randomized multicentre study conducted between 2018-2022 in seven tertiary medical centres, consecutive patients with cDI and PP underwent diagnostic evaluation with hypertonic saline and arginine stimulation. Serum copeptin levels were measured at sodium-level of &amp;gt;149 mmol/L after hypertonic saline and 60 minutes after arginine infusion, respectively. The final diagnosis was made after treatment response assessment at three-month follow-up blinded to copeptin levels. The main outcome measure was the overall diagnostic accuracy using the pre-defined copeptin cut-off of 4.9 pmol/L for hypertonic saline and 3.8 pmol/L for arginine stimulation. Results: 158 patients underwent both tests, of which 69 (44%) were diagnosed with cDI and 89 (56%) with PP. Forty-one (59%) patients had a complete and 28 (41%) patients had partial cDI. The diagnostic accuracy [95% CI] to differentiate patients with cDI from patients with PP was 95.6% [91.1,97.8] for hypertonic saline stimulated copeptin compared to 74.4% [67.0, 80.6] for arginine stimulated copeptin. Accordingly, arginine stimulation was inferior to hypertonic saline stimulation (estimated difference [95% CI] -21.2% [-28.7, -14.3]). Side effects were less frequent and less severe under arginine stimulation, resulting in a clear 72% of patients preferring the arginine stimulation over hypertonic saline stimulation. In addition, arginine stimulated copeptin of 3.0 pmol/L diagnosed cDI with a specificity of 90.9% (sensitivity of 59.5%), while a cut-off of 5.2 pmol/L diagnosed PP with a specificity of 91.4% (sensitivity of 56.4%). Conclusion: In the diagnostic evaluation of cDI, copeptin upon hypertonic saline stimulation was superior to arginine stimulation. Arginine stimulation can be used as a first well-tolerated test diagnosing &amp;gt;50% of patients with high accuracy, but hypertonic saline stimulation remains the test with the highest diagnostic accuracy. Presentation: Saturday, June 17, 2023

Relationship between adiponectin and copeptin levels with long-term cardiovascular mortality in ST-segment elevation myocardial infarction after percutaneous coronary intervention.

The aim of this study was to determine adiponectin and copeptin levels that might be prognostic for cardiovascular mortality (CvsM) in ST-segment elevation myocardial infarction (STEMI) patients who had percutaneous coronary intervention (PCI). Patients who underwent PCI between November 2010 and April 2011 were enrolled and followed for more than eight years. The baseline, demographic and angiographic findings, in-hospital follow up, laboratory results including adiponectin and copeptin levels, and echocardiographic data of the patients were evaluated. There were 78 males and 20 females. The CvsM rate was 26.66% at 112 months of follow up. Some factors were significantly related to CvsM and adiponectin level was an independent predictor of mortality. A cut-off value of ≥ 8 950 ng/ml for adiponectin and ≥ 7.41 ng/ml for copeptin was related to a 3.01- and 2.83-times higher CvsM risk, respectively. Adiponectin level was a predictor for CvsM. Higher levels of adiponectin and copeptin could predict a higher risk of CvsM in STEMI patients.