Low Copeptin Research Articles

Arginine-stimulated copeptin in children and adolescents.

Copeptin is secreted in isomolar amounts along with arginine vasopressin peptide (AVP) from the neurohypophysis. Its stability makes it a perfect candidate for the endocrine approach in the diagnosis of AVPdeficiency (AVPD; cranial diabetes insipidus; CDI). However, pediatric reference values are lacking. This is a monocentric retrospective analysis of donated residual serum samples from 72 children and adolescents who underwent arginine or growth hormone-releasing hormone-arginine stimulation to test GH secretory capacity from 2018 to 2022. Copeptin was measured in baseline, 30-, and 60-min samples by BRAHMS Copeptin proAVP Kryptor immunofluorescence assay. Of the 72 patients, 4 suffered from complete AVPD (CDI). The baseline level of copeptin in the 68 non-AVPD (non-CDI) patients was highly variable (range: 1.3-44.4 pmol/L). The increase after arginine was moderate (30 min range: 1.6-40.4 pmol/L). The median baseline and peak copeptin levels were 5.6 and 8.0 pmol/L, respectively. The 2.5th percentile of the baseline and peak values of copeptin were 2.1 and 3.3 pmol/L, respectively. The increase and peak value of copeptin were inversely related to age (R = -.405; p = .011, and R = -.335; p = .0072, respectively) but not to gender, body mass index(standard deviation score) or GH secretion. In the four patients with AVPD (CDI), baseline or stimulated copeptin was below the 2.5th percentile of non-AVPD (non-CDI) patients. Stimulated copeptin is a promising parameter for the differential diagnosis of polyuria-polydipsia syndrome. However, the low copeptin increase after arginine and the high limit of quantification of the assay are problematic for use in paediatrics.

RF25 | PMON113 Subarachnoid Hemorrhage Complicated by Nephrogenic and Central Diabetes Insipidus

Abstract Introduction Diabetes insipidus (DI) is a rare complication of subarachnoid hemorrhage (SAH) and associated with worse prognosis and increased mortality. We present a case of combined nephrogenic and central DI together with osmotic diuresis as a result of SAH and discuss the pathophysiology. Case A 63-year-old female without significant past medical history was found unresponsive. CT head followed by angiography confirmed extensive SAH arising from a saccular anterior communicating artery (Acoma) aneurysm. She underwent emergent coil embolization and right frontal external ventriculostomy drain placement. Postoperatively, she developed polyuria (300-400 mL/hour) and hypernatremia (156 mEq/L) concerning for the development of DI. Serum osmolality was elevated at 316 mOsm/kg, urine osmolality inappropriately low relative to serum osmolality at 289 mOsm/kg but also unexpectedly high for complete DI, serum potassium 2.9 mEq/L and urine potassium elevated urine at 9 mEq/L. Serum copeptin was 6 pmol/L and inappropriately low for nephrogenic DI, suggesting a mixed central and peripheral process as well as contribution from osmotic diuresis. Intravenous (IV) desmopressin (DDAVP) only slightly reduced the polyuria. Management was complicated by adypsia and persistent hypokalemia requiring ongoing replacement. IV fluid, which had initially consisted of high-osmolality Plasma-Lyte (294 mOsm/L), matched to urine output, was switched to D5W, leading to a significant decrease in polyuria. On post-operative day 17, DDAVP was discontinued with normalization of sodium (137 mEq/L), potassium (3.8 mEq/L) and urine output. Three months post-operatively, she was asymptomatic with intact pituitary function and no hypokalemia. Discussion Hypokalemia in patients with SAH is thought due to acute intracellular shift of potassium caused by excessive β2-adrenergic activity generated endogenously by the sympathetic nervous system. In our patient, there was also likely contribution from distal tubular delivery of sodium from osmotic diuresis, leading to increased urinary potassium losses and hypokalemia-induced partial nephrogenic DI which was further complicated by partial central DI as suggested by the inappropriately low copeptin level for nephrogenic DI in face of a high serum osmolality and inappropriately low urine osmolality. As the vascular supply to anterior hypothalamus is derived from the Acoma, rupture may compromise perfusion affecting neuronal populations in the lamina terminalis that regulate thirst and AVP secretion in response to hyperosmolarity. Early detection of DI is critical because hypovolemia can predispose to cerebral vasospasm and worsen outcomes. This case also depicts the importance of careful consideration of sources of osmolar loads such as the composition of administered IV fluids, and aggressive potassium replacement to maintain DDAVP sensitivity. Conclusion DI should be considered in polyuria syndrome with hypernatremia after a neurosurgical event. Nephrogenic and central DI and adypsia can manifest following SAH, with sources of iatrogenic osmolar load further complicating the clinical picture. Early recognition and treatment may reduce morbidity and mortality. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.

Copeptin Release in Arterial Hypotension and Its Association with Severity of Disease in Critically Ill Children.

Low copeptin levels may indicate inadequate arginine-vasopressin release promoting arterial hypotension, whereas high copeptin concentrations may reflect disease severity. This single-center prospective non-randomized clinical trial analyzed the course of blood copeptin in critically ill normo- and hypotensive children and its association with disease severity. In 164 patients (median age 0.5 years (interquartile range 0.1, 2.9)), the mean copeptin concentration at baseline was 43.5 pmol/L. Though not significantly different after 61 h (primary outcome, mean individual change: −12%, p = 0.36, paired t-test), we detected 1.47-fold higher copeptin concentrations during arterial hypotension when compared to normotension (mixed-effect ANOVA, p = 0.01). In total, 8 out of 34 patients (23.5%) with low copeptin concentrations <10 pmol/L were hypotensive. Copeptin was highest in the adjusted mixed-effect regression analysis within the first day (+20% at 14 h) and decreased significantly at 108 h (−27%) compared to baseline (p = 0.002). Moreover, we found a significant association with vasopressor-inotrope treatment intensity, infancy (1–12 months) and cardiopulmonary bypass (all p ≤ 0.001). In conclusion, high copeptin values were associated with arterial hypotension and severity of disease in critically ill children. This study does not support the hypothesis that low copeptin values might be indicative of arginine-vasopressin deficiency.

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 levels predict left ventricular systolic function in STEMI patients: A 2D speckle tracking echocardiography-based prospective observational study.

In the present study, we aimed to investigate whether copeptin values on admission are related to left ventricle (LV) systolic function and its improvement at 6 months in ST-segment elevation myocardial infarction (STEMI) patients.In this single-center, prospective observational study, we included 122 STEMI patients from January 2016 to November 2016. LV systolic functions in the form of global longitudinal strain (GLS) in addition to conventional echocardiography parameters were evaluated on admission and at 6-month. Serum copeptin levels were determined using an ultrasensitive immunofluorescence assay.The study population was divided into 2 groups according to median values of copeptin. GLS was significantly lower in patients with high copeptin levels compared to those with low copeptin levels at early stage and 6-month (−16% (16–16.5) vs −15% (15–15.5), P < .001 and −18% (18–19) vs −16% (16–16.25), P < .001, respectively). Copeptin values were negatively correlated with an early and 6-month GLS (r = –0.459 at early stage and r = –0.662 at 6-month). In addition, we observed that copeptin values were negatively correlated with the improvement of GLS at 6-month follow-up (r = −0.458, P < .001 and r = −0.357, P = .005, respectively).Serum copeptin levels in STEMI patients at the time of admission may predict early and 6-month LV systolic function assessed by two-dimensional GLS. To the best of our knowledge, this study is the first to specifically address the relationship between copeptin values and GLS in STEMI patients.

Vasopressin associated with renal vascular resistance in adults with longstanding type 1 diabetes with and without diabetic kidney disease.

Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors. Participants with type 1 diabetes (n = 62, duration ≥50 years) were stratified into 42 DKD Resistors and 20 with DKD (eGFR ≤60 mL/min/1.73m2 or ≥30 mg/day urine albumin), and age/sex-matched controls (HC, n = 74) were included. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were calculated by inulin and p-aminohippurate clearance before and after angiotensin II (ang II) infusion. Renal vascular resistance (RVR) was calculated as mean arterial pressure/renal blood flow. Plasma copeptin, renin, aldosterone, neutrophil gelatinase-associated lipocalin (NGAL), and urea concentrations were measured, along with 24-h urine volume. DKD resistors had lower copeptin (95% CI: 4.0 [3.4-4.8] pmol/l) compared to DKD (5.8 [4.5-7.6] pmol/l, p = 0.02) and HC (4.8 [4.1-5.5] pmol/l, p = 0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: -0.32, p = 0.01) and higher renin concentration (r: 0.40, p = 0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (β ± SE: -6.9 ± 3.4, p = 0.04). In longstanding type 1 diabetes, copeptin was associated with intrarenal renin-angiotensin-aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.

Copeptin concentration following cardiac surgery as a prognostic marker of postoperative acute kidney injury: a prospective cohort study.

BackgroundCopeptin, the C-terminal portion of the arginine vasopressin precursor, is a novel candidate biomarker. This study investigated the prognostic value of copeptin levels following cardiac surgery for the occurrence of postoperative acute kidney injury.MethodsWe studied 23 patients who underwent cardiac surgery between January 2018 and December 2019. The primary endpoint was postoperative acute kidney injury onset. Copeptin levels were measured before, right after, and daily for 7 days. The patients were divided into two groups according to the copeptin levels: low (values <43.7 pmol/L) and high (values ≥43.7 pmol/L). Correlations between copeptin levels and variables, such as central venous pressure, were assessed by bivariate analysis.ResultsThe high copeptin group exhibited significantly higher levels of arginine vasopressin and cortisol following surgery, compared to those of the low copeptin group. The copeptin concentration following surgery was correlated to central venous pressure (P=0.03) and norepinephrine administered dose (P=0.008). Also, the copeptin levels right after surgery robustly predicted the onset of postoperative acute kidney injury (area under the receiver operating characteristic curve of 0.83, P=0.004).ConclusionsElevated copeptin levels in patients following cardiac surgery predicted postoperative acute kidney injury development. Therefore, the copeptin concentration after surgery could represent a promising clinical biomarker of the postoperative cardiac outcome.

Prognostic performance of copeptin among patients with acute decompensated heart failure

Background In heart failure (HF), various biomarkers have been established for prognosis. However, little is known about the relevance of copeptin measurements to HF. This study aimed to explore the prognostic value of copeptin for predicting cardiovascular (CV) death or HF-related re-hospitalisation in patients with acute decompensated HF. Materials and Methods We prospectively enrolled 155 consecutive patients with acute signs and symptoms of HF. Plasma copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission. Patients were monitored for 90 days regarding the composite endpoint of CV death or acute HF-related re-hospitalisation. Results Of the 155 patients enrolled, 40 reached the endpoint, and 115 were in a stable condition during follow-up. Patients who reached an adverse endpoint showed higher NT-proBNP and copeptin levels compared to patients in stable condition. Receiver operating characteristic curve analysis revealed that the area under curve of copeptin 0.844 (95% CI, 0.753–0.935) was superior to that of NT-proBNP 0.809 (95% CI, 0.729–0.890) for the prediction of adverse events within 90 days. Meanwhile, compared to the group with lower copeptin levels (<34 pmol/L), patients with higher copeptin levels (≥34 pmol/L) were at a 10.672-times higher risk of CV death or acute HF-related re-hospitalisation. Multivariate Cox proportional hazards regression analysis revealed that increased copeptin level was a significantly independent predictor of adverse events (risk ratio, 1.051; 95% CI, 1.020–1.083; p < 0.001). Conclusion Copeptin was found to be a strong, novel marker for predicting CV death or HF-related re-hospitalisation in patients with acute decompensated HF.

Biomarkers in patients with Takotsubo cardiomyopathy compared to patients with acute anterior ST-elevation myocardial infarction

Background: Takotsubo cardiomyopathy (TTC) is a syndrome of acute non-coronary heart failure with similar symptoms and electrocardiograms to acute anterior ST-elevation myocardial infarction (STEMI). Little is known about the pathophysiology of TTC. We assessed admission plasma concentrations of biomarkers reflecting neuroendocrine response (copeptin, mid-regional-pro-adrenomedullin, pro-atrial-natriuretic-peptide, soluble thrombomodulin (sTM), syndecan-1) and inflammation (suppression-of-tumorigenicity 2 (ST2), high-sensitive C-reactive-protein) in TTC patients and compared to patients with acute anterior STEMI.Materials and methods: Twenty TTC patients were matched with 40 STEMI patients by age, gender and left ventricular ejection fraction. Blood was sampled upon hospital admission immediately before acute coronary angiography.Results: The groups had similar comorbidities. TTC patients had higher plasma concentrations of sTM: 7.94 (5.89;9.61) vs. 6.42 (5.50;7.82)ng/ml, p = 0.04 and ST2 (53 (32;157) vs. 45 (31;55)ng/ml, p = 0.008) and higher heart rate: 101 (33) vs. 76(14)bpm, p = 0.0001, but lower concentrations of copeptin (10.4 (7.6;39) vs. 92.3 (13;197)pmol/l, p < 0.05) and troponin T (348 (98;759) vs. 1190 (261;4105)ng/l, p = 0.04).Conclusion: TTC patients had higher plasma concentrations of sTM and ST2, higher heart rate and lower copeptin and troponin T concentrations compared to acute anterior STEMI patients. This study contributes to the hypothesis that TTC patients have endothelial cell damage and are hemodynamically more stable than patients with acute anterior STEMI on admission.

538-P: Copeptin and Renin Angiotensin Aldosterone System (RAAS) Activation in Long-Standing Type 1 Diabetes (T1D)

It remains unclear why some individuals with long-standing T1D develop diabetic kidney disease (DKD) while others do not (DKD resistors). Vasopressin and its surrogate copeptin have been implicated in the pathogenesis of DKD. We hypothesized that DKD resistors would be distinguished from those with DKD by copeptin concentrations. Renal hemodynamic function, including renal vascular resistance (RVR), was measured by inulin and para-aminohippurate clearance at baseline and after intravenous infusion of angiotensin II as a measure of RAAS activation in 75 participants (65±8 years, HbA1c 7.4±0.8%) with prolonged T1D durations (≥50 years) and in equal numbers of nondiabetic controls (66±8 years). Copeptin was measured by B·R·A·H·M·S proAVP copeptin KRYPTOR assay. Participants with T1D were categorized as DKD resistors (n=50) if they had eGFR ≥60 ml/min/1.73 m2 and 24-hour urine albumin excretion (UAE) &amp;lt;30 mg/d, and as DKD (n=25) if they had eGFR &amp;lt;60 ml/min/1.73 m2 or 24-hour UAE &amp;gt;30 mg/d at their screening visit. Multivariable linear regression (adjusted for age, sex and HbA1c) was used to evaluate the relationships with copeptin. DKD resistors had lower copeptin (least square geometric means, 95% CI: 4.0 [3.4-4.8] pmol/l) compared to those with DKD (5.8 [4.5-7.6] pmol/l, p=0.02) and the nondiabetic controls (4.8 [4.1-5.5] pmol/l, p=0.01) adjusting for age, sex and HbA1c. In T1D, copeptin inversely associated with GFR (adjusted β±SE: -8.0±3.2, p=0.02) and positively with renin concentration (50.3±24.9, p=0.049) after multivariable adjustments. These relationships were not evident in nondiabetic controls. Further, copeptin inversely associated with change in RVR following exogenous angiotensin II only in participants with T1D (adjusted β±SE: -6.9±3.4, p=0.04). In longstanding T1D, copeptin associated with intrarenal RAAS activation and renal hemodynamic function, suggesting a possible interplay between vasopressin and RAAS in the pathogenesis of DKD. Disclosure P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. J.A. Lovshin: Consultant; Self; Eli Lilly and Company, Intarcia Therapeutics, Inc., Prometic Life Sciences Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Y. Lytvyn: None. P. Wiromrat: None. L.T. Chung: None. C.L. Vinovskis: None. L. Lovblom: None. G. Boulet: Other Relationship; Self; Medtronic. V.S. Lai: None. J.M. Tse: None. L. Cham: None. A. Orszag: None. A. Weisman: None. H.A. Keenan: Employee; Self; Sanofi Genzyme. M.H. Brent: Advisory Panel; Self; AbbVie Inc., Bayer Canada, Novartis Canada. Research Support; Self; Bayer Canada, Novartis Canada, Roche Canada. N. Paul: Consultant; Self; Bayer AG. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alexion Pharmaceuticals, Inc., Alnylam, CSL Behring. Consultant; Self; Pfizer Inc. Research Support; Self; Baxter, Biogen, Grifols, UCB, Inc. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. Funding JDRF (17-2013-312, 2-SRA-2018-627-M-B)

Low Copeptin Levels in Patients With Intradialytic Hypotension.

Intradialytic hypotension (IDH) is related to high morbidity and mortality. There is evidence that arginine-vasopressin (AVP) responses could play a role. Copeptin is a reliable biomarker of AVP. In this study, copeptin, aldosterone, epinephrine, and norepinephrine levels in patients with IDH were evaluated throughout a hemodialysis (HD) session and compared with the control group. The study includes 15 patients who were normotensive during HD and 15 patients with IDH with a minimum HD vintage of 1 year. Blood samples were collected before the initiation of an HD session (T0 ), in the mid-session for control group, 30 min after mean arterial pressure drop for IDH patients (T1 ), and at the end of the session (T2 ). Groups had similar demographic features and health parameters, interdialytic weight gains, and ultrafiltration amounts. The IDH group had a mean arterial pressure decline of 39.9 (±6.4) mm Hg. Copeptin levels of the control group increased an average of 79.9 (±97.5) pmol/L at T1 and an additional 24.8 (±33.9) pmol/L at T2 . In the IDH group, copeptin level increases at T1 and T2 were 3.2 (±5.5) pmol/L and 34 (±44.6) pmol/L, respectively. Copeptin levels of the IDH group were significantly lower at T1 (P < 0.001) and at the T0 -T2 interval than control group (P = 0.05). In the control group, aldosterone levels distinctly decreased, and in the IDH group, aldosterone levels were elevated (P < 0.001). Small changes were detected in epinephrine and norepinephrine levels for both groups but did not reach significance (P = 0.6 and P = 0.3, respectively). Lower copeptin level alterations suggest inadequate AVP responses in patients with IDH.

Evaluation of copeptin and commonly used laboratory parameters for the differential diagnosis of profound hyponatraemia in hospitalized patients: 'The Co-MED Study'.

Hyponatraemia is common and its differential diagnosis is challenging. Commonly used diagnostic algorithms have limited diagnostic accuracy. Copeptin, the c-terminal portion of the precursor peptide of arginine vasopressin might help in the differential diagnosis of hyponatraemia. Prospective multicentre observational study. A total of 298 patients admitted with profound hypoosmolar hyponatraemia (Na < 125 mmol/l) were evaluated. Three experts uninvolved in the patients' care determined the aetiology of hyponatraemia after standardized diagnostic evaluation. Hyponatraemia differential diagnoses were as follows: syndrome of inappropriate antidiuresis (SIAD), 106 patients (35·6%); 'diuretic-induced', 72 (24·2%); 'hypovolaemic', 59 (19·8%); 'hypervolaemic', 33 (11·1%); primary polydipsia (PP), 24 (8·1%); and cortisol deficiency, 4 (1·3%). Copeptin levels <3·9 pmol/l identified patients with PP with high specificity (91%). Further, copeptin levels >84 pmol/l were highly predictive for hypovolaemic hyponatraemia (specificity: 90%). Urinary sodium levels and copeptin/urinary sodium ratio in patients with SIAD were higher and lower as compared to other hyponatraemia aetiologies (P < 0·0001). However, the specificity to identify SIAD was moderate for both parameters (31% and 61%). Fractional uric acid excretion (FEUA ) and fractional urea excretion (FEurea ) were higher in patients with SIAD compared to other hyponatraemia aetiologies (both P < 0·0001). FEurea values >55% and FEUA values >12% had a specificity of 96% and 77% to detect patients with SIAD. These results remained similar after excluding patients taking diuretics. Overall, there is only limited diagnostic utility of copeptin in the differential diagnosis of profound hyponatraemia. Very low copeptin levels are seen in patients with PP and highest copeptin levels in hypovolaemic hyponatraemia. To discriminate between SIAD and other hyponatraemia aetiologies, FEurea and FEUA levels are valuable irrespective of diuretics use.

Less increase of copeptin and MR‐proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4‐year prospective randomized double‐blind placebo‐controlled trial among elderly Swedish citizens

Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MR-proADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P = 0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P = 0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P = 0.0001, and P = 0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MR-proADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation.

Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery.

Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation. The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery. This was a prospective multicenter observational cohort study. Three Swiss or Canadian referral centers were used. Consecutive pituitary surgery patients were included. Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI. Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1. Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points. In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.

Low Copeptin Levels Effectively Ruled Out MI

Low Copeptin Levels Effectively Ruled Out MI