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      Distribution of plasma copeptin levels and influence of obesity in children and adolescents

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          Abstract

          In recent years, a more stable AVP surrogate, called copeptin, has been used as an adjuvant diagnostic tool for dysnatremia in adults and appears to be promising even in the pediatric age. The aim of this study is to present the distribution of plasma copeptin in a large pediatric cohort and to observe the influence of fluid consumption and obesity on its values. A cohort of 128 children and adolescents was divided into two groups on the basis of nocturnal deprivation (group A) or free access to oral fluids in the 6–8 h before blood collection (group B). At all distribution percentiles, copeptin levels were higher ( p < 0.0001) in group A, as were plasma sodium levels and osmolality ( p = 0.02 and p = 0.008, respectively). The influence of BMI on copeptin levels was investigated by dividing the cohort into nonobese (group C) and obese children and adolescents (group D). Copeptin levels were higher in group D ( p = 0.04).

          Conclusion: The measurement of copeptin could represent a useful tool for the diagnostic pathway of dysnatremic conditions, but its interpretation should take into consideration the state of hydration. Furthermore, it could also be a promising marker for obesity and metabolic syndrome, although this hypothesis needs further studies to be confirmed.

          What is Known:

          Copeptin use as a diagnostic tool in AVP-related disorders, such as diabetes insipidus or syndrome of inappropriate secretion of antidiuretic hormone, is well established in adults

          In pediatric age, few studies are available, but the preliminary data, including our previous study, seems to be promising.

          What is New:

          In this study, we represent the distribution of copeptin levels in a pediatric cohort and show the significant influence of fluid ingestion on its plasma levels.

          Also BMI seems to be a significant variable on copeptin levels and may be used as an obesity marker in pediatric age

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          Most cited references65

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          Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity : Extended international BMI cut-offs

          The international (International Obesity Task Force; IOTF) body mass index (BMI) cut-offs are widely used to assess the prevalence of child overweight, obesity and thinness. Based on data from six countries fitted by the LMS method, they link BMI values at 18 years (16, 17, 18.5, 25 and 30 kg m(-2)) to child centiles, which are averaged across the countries. Unlike other BMI references, e.g. the World Health Organization (WHO) standard, these cut-offs cannot be expressed as centiles (e.g. 85th). To address this, we averaged the previously unpublished L, M and S curves for the six countries, and used them to derive new cut-offs defined in terms of the centiles at 18 years corresponding to each BMI value. These new cut-offs were compared with the originals, and with the WHO standard and reference, by measuring their prevalence rates based on US and Chinese data. The new cut-offs were virtually identical to the originals, giving prevalence rates differing by < 0.2% on average. The discrepancies were smaller for overweight and obesity than for thinness. The international and WHO prevalences were systematically different before/after age 5. Defining the international cut-offs in terms of the underlying LMS curves has several benefits. New cut-offs are easy to derive (e.g. BMI 35 for morbid obesity), and they can be expressed as BMI centiles (e.g. boys obesity = 98.9th centile), allowing them to be compared with other BMI references. For WHO, median BMI is relatively low in early life and high at older ages, probably due to its method of construction. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.
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            Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin.

            Arginine vasopressin (AVP) is a key regulator of water balance, but its instability makes reliable measurement difficult and precludes routine use. We present a method for quantifying AVP release by use of copeptin, a glycopeptide comprising the C-terminal part of the AVP prohormone. We measured copeptin in 50-microL serum and plasma samples from healthy individuals and from critically ill patients with sepsis. Our sandwich immunoluminometric assay used 2 polyclonal antibodies to amino acids 132-164 of pre-provasopressin. The assay yielded results within 3 h. The analytical detection limit was 1.7 pmol/L, and the interlaboratory CV was 2.25 pmol/L. The assay was linear on dilution of the analyte. Ex vivo copeptin stability (<20% loss of analyte) for at least 7 days at room temperature and 14 days at 4 degrees C was shown for serum and EDTA-, heparin-, and citrate plasma. Copeptin (median, 4.2 pmol/L; range, 1-13.8 pmol/L) was detectable in 97.5% of 359 healthy individuals and was not associated with age. Median concentrations were considerably higher in men than women, increased significantly after exercise, and were influenced by fasting and water load. Copeptin was significantly (P <0.001) increased in 60 critically ill patients with sepsis (median, 79.5 pmol/L; range, 10.6-228.0 pmol/L). The correlation between copeptin and AVP for 110 samples was r = 0.78 (P <0.0001). Copeptin is stable for days after blood withdrawal and can be quickly and easily measured. The copeptin assay may be a useful alternative to direct measurement of AVP concentration.
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              Vasopressin: physiology, assessment and osmosensation

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                Author and article information

                Contributors
                gerdi.tuli@unito.it
                jessica.munarin@edu.unito.it
                daniele.tessaris@unito.it
                seinaudi@cittadellasalute.to.it
                pmatarazzo@cittadellasalute.to.it
                luisa.desanctis@unito.it
                Journal
                Eur J Pediatr
                Eur J Pediatr
                European Journal of Pediatrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-6199
                1432-1076
                18 August 2020
                18 August 2020
                2021
                : 180
                : 1
                : 119-126
                Affiliations
                [1 ]GRID grid.415778.8, Department of Pediatric Endocrinology, , Regina Margherita Children’s Hospital, ; Turin, Italy
                [2 ]GRID grid.7605.4, ISNI 0000 0001 2336 6580, Department of Public Health and Pediatric Sciences, , University of Turin, ; Turin, Italy
                [3 ]Turin, Italy
                Author notes

                Communicated by Peter de Winter

                Author information
                http://orcid.org/0000-0001-5862-8958
                Article
                3777
                10.1007/s00431-020-03777-3
                7782451
                32809080
                4e60248b-ba52-42b3-b111-9126fc74df6d
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 April 2020
                : 4 August 2020
                : 10 August 2020
                Funding
                Funded by: Università degli Studi di Torino
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                Pediatrics
                copeptin,distribution,avp related disorders,pediatric age,obesity
                Pediatrics
                copeptin, distribution, avp related disorders, pediatric age, obesity

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