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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Renal Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1397384
This article is part of the Research Topic Endocrine Regulation of Homeostasis of Water, Electrolytes and Organic Solutes View all 3 articles

Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency and primary polydipsia data from the CARGO and CARGOx studies

Provisionally accepted
Cihan Atila Cihan Atila 1*Sven Lustenberger Sven Lustenberger 1Irina Chifu Irina Chifu 2Emanuele Ferrante Emanuele Ferrante 3Zoran Erlic Zoran Erlic 4Juliana Drummond Juliana Drummond 5Rita Indirli Rita Indirli 3Roosmarijn Drexhage Roosmarijn Drexhage 6Andrew S Powlson Andrew S Powlson 7Mark Gurnell Mark Gurnell 7Beatriz Santana Soares Beatriz Santana Soares 5Johannes Hofland Johannes Hofland 6Felix Beuschlein Felix Beuschlein 4Martin Fassnacht Martin Fassnacht 2Bettina Felicitas Winzeler Bettina Felicitas Winzeler 1Julie Refardt Julie Refardt 1Mirjam Christ-Crain Mirjam Christ-Crain 1*
  • 1 University Hospital of Basel, Basel, Switzerland
  • 2 University Hospital Würzburg, Würzburg, Bavaria, Germany
  • 3 IRCCS Ca 'Granda Foundation Maggiore Policlinico Hospital, Milan, Lombardy, Italy
  • 4 University Hospital Zürich, Zurich, Zürich, Switzerland
  • 5 Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
  • 6 Erasmus Medical Center, Rotterdam, Netherlands
  • 7 University of Cambridge, Cambridge, England, United Kingdom

The final, formatted version of the article will be published soon.

    Background Arginine infusion stimulates copeptin secretion, a surrogate marker of arginine vasopressin (AVP), thereby serving as a diagnostic test in the differential diagnosis of suspected AVP deficiency (AVP-D). Yet, the precise mechanism underlying the stimulatory effect of arginine on the vasopressinergic system remains elusive. Arginine plays a significant role in the urea cycle and increases the production of urea. An increase in plasma urea concentration raises blood osmolality, thereby possibly stimulating AVP release.We therefore hypothesized that the stimulatory effect of arginine on AVP may involve an increase in plasma urea levels.Methods This analysis combined data from two prospective diagnostic studies. In total, 30 healthy adults (HA), 69 patients with AVP-D, and 89 patients with primary polydipsia (PP) underwent the arginine stimulation test. Infusion of arginine (L-arginine-hydrochloride 21%) at a dose of 0.5 g/kg body weight diluted in 500 ml of 0.9% normal saline was administered over 30 minutes. Blood was collected at baseline and 60, 90, and 120 minutes to analyze plasma copeptin and urea. The main objective was to investigate urea dynamics in response to arginine administration and its effect on copeptin release.Plasma urea levels at baseline were comparable and increased 60 minutes after arginine infusion with a median (IQR) change of +1.1 mmol/L (+0.8, +1.5) in HA, +1.4 mmol/L (+1.1, +1.7) in patients with AVP-D and +1.3 mmol/L (+0.9, +1.5) in patients with PP. Concurrently, plasma copeptin levels substantially increased 60 minutes from baseline in HA (median change +5.3 pmol/L (+3.2, + 8.8)) and in patients with PP (median change + 2.4 pmol/L (+1.2, +3.8)), but remained stable in patients with AVP-D (median change +0.3 pmol/L (+0.1, +0.6)). Plasma urea and copeptin levels correlated the most in HA, with a Spearman's rho of 0.41 at baseline. Patients with AVP-D and PP showed only weak correlations of plasma urea and copeptin, with a correlation coefficient between 0.01 and 0.28.We demonstrate a slight increase in plasma urea levels in response to arginine, but plasma urea and copeptin levels were weakly correlated. Based on these findings, the stimulatory effect of arginine on AVP cannot be explained primarily by increasing urea levels.

    Keywords: Arginine Vasopressin, posterior pituitary, Stimulation test, polyuria polydipsia, Diabetes Insipidus, Pituitary

    Received: 07 Mar 2024; Accepted: 20 Nov 2024.

    Copyright: © 2024 Atila, Lustenberger, Chifu, Ferrante, Erlic, Drummond, Indirli, Drexhage, Powlson, Gurnell, Soares, Hofland, Beuschlein, Fassnacht, Winzeler, Refardt and Christ-Crain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Cihan Atila, University Hospital of Basel, Basel, Switzerland
    Mirjam Christ-Crain, University Hospital of Basel, Basel, Switzerland

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