Evidence map›Paper›PMID 39863827›Full record

ArticlePituitary2025

Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency and primary polydipsia.

Cihan Atila, Sven Lustenberger, Irina Chifu, Emanuele Ferrante, Zoran Erlic, Juliana B Drummond, Rita Indirli, Roosmarijn Drexhage, Andrew S Powlson, Mark Gurnell and 7 more

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Article in Pituitary, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Cihan Atila *Departments of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
Sven Lustenberger *Departments of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
Irina ChifuDivision of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, Wurzburg, Germany.
Emanuele FerranteEndocrinology Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.
Zoran ErlicDepartment of Endocrinology, Diabetology, and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland.
Juliana B DrummondDepartment of Internal Medicine, Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Rita IndirliEndocrinology Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.
Roosmarijn DrexhageSection of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Andrew S PowlsonInstitute of Metabolic Science, University of Cambridge and Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge, UK.
Mark GurnellInstitute of Metabolic Science, University of Cambridge and Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge, UK.
Beatriz Santana SoaresDepartment of Internal Medicine, Medical School of the Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Johannes HoflandSection of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Felix BeuschleinDepartment of Endocrinology, Diabetology, and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland.
Martin FassnachtDivision of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, Wurzburg, Germany.
Bettina WinzelerDepartments of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
Julie RefardtDepartments of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
Mirjam Christ-CrainDepartments of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. mirjam.christ-crain@usb.ch.

Funding

Fundação de Amparo à Pesquisa do Estado de Minas Gerais FAPEMIG-APQ-01521-21Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 32473B_162608
6 · The paper itself

Abstract

backgroundArginine 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.

methodsThis 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 min. Blood was collected at baseline and 60, 90, and 120 min 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.

resultsPlasma urea levels at baseline were comparable and increased 60 min 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 min 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.

conclusionWe 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.

Indexed as

ArginineArginine VasopressinGlycopeptidesPolydipsiaPolydipsia, PsychogenicUreaVasopressinsAdultFemaleHumansMaleMiddle AgedProspective StudiesYoung AdultArginineArginine VasopressincopeptinsGlycopeptidesUreaVasopressinsArginine vasopressinDiabetes insipidusPituitaryPolyuria polydipsiaPosterior pituitaryStimulation test

Identifiers

PMID39863827
PMCPMC11762438

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.