Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study

Winzeler, Bettina; Cesana-Nigro, Nicole; Refardt, Julie; Vogt, Deborah R; Imber, Cornelia; Morin, Benedict; Popović, Milica; Steinmetz, Michelle; Sailer, Clara O; Szinnai, Gabor; Chifu, Irina; Fassnacht, Martin; Christ‐Crain, Mirjam

doi:10.1016/s0140-6736(19)31255-3

Cited by 102 publications

(85 citation statements)

References 24 publications

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“…It has proven to be very useful in the distinction of hypernatremic conditions (such as CDI, NDI, and PP) and less useful in hyponatremia due to the important overlap between SIADH, hyper-or hypovolemic hyponatremia [35][36][37][38][39][40][41][42][43][44][45][46][47], a finding already reported also in a small number of pediatric patients [42]. In adults, it seems to be a promising diagnostic tool even after stimulation tests with hypertonic saline or arginine, not yet explored in children [48,49].…”

Section: Introductionmentioning

confidence: 97%

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

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 97%

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

et al. 2020

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“…A total of 46 patients with cDI or PP and 30 healthy volunteers were included at the University Hospital of Basel, Switzerland, between 2017 and 2018. Participants underwent an arginine stimulation test with measurements of copeptin at baseline and at different time points thereafter (NCT01940614) 10 …”

Section: Methodsmentioning

confidence: 99%

“…For copeptin analysis, blood was drawn and immediately centrifuged and stored at −80°C. After the initial blood withdrawal, diagnostic tests were performed according to the respective study protocols 10,11 …”

Section: Methodsmentioning

confidence: 99%

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia

Winzeler

Morin

Refardt

et al. 2020

Clinical Endocrinology

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Objective Arginine vasopressin (AVP) is released upon osmotic stimulation or hypovolaemia in order to maintain water balance. A recent study showed a role of AVP in haematopoiesis by stimulating red blood cell precursors, suggesting a higher risk of anaemia in patients with AVP deficiency. The objective was to explore the effect of low AVP levels in patients with central diabetes insipidus (cDI) and primary polydipsia (PP) on haemoglobin and the prevalence of anaemia. Methods A total of 164 patients with either cDI (70, 43%) or PP (94, 57%) and 30 healthy volunteers from two prospective diagnostic studies performed in Switzerland, Germany and Brazil were studied. A standardized clinical and biochemical (eg copeptin, full blood count) assessment was performed. Haemoglobin and haematocrit levels and prevalence of anaemia (defined as haemoglobin values of <120 g/L in women and <130 g/L in men) were analysed. Results Mean copeptin values were 2.63 pmol/L (±1.08) and 3.91 pmol/L (±4.28) in patients with cDI and PP and 24.76 pmol/L (±5.75) in healthy volunteers, P = .02. The prevalence of anaemia was low in all participants with 7.1%, 2.2% and 10% in cDI, PP and in healthy volunteers, P = .15. Mean haemoglobin values were similar in all groups: 139 g/L (±15.85), 140 g/L (±13.16) and 139 g/L (±13.05) in patients with cDI, PP and healthy volunteers, P = .90, as were mean haematocrit values with 41% in all groups (P = .85). Conclusion Chronic low AVP levels in patients with cDI and PP do not affect haemoglobin levels and prevalence of anaemia.

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“… Copeptin after arginine infusion, in patients with complete or partial central DI and in primary polydipsia. Adapted from [40]. DI, diabetes insipidus.…”

Section: Second Concept: Nonosmotic Stimulation With Arginine Plus Comentioning

confidence: 99%

Diabetes Insipidus: New Concepts for Diagnosis

Christ-Crain

2020

Neuroendocrinology

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Diabetes insipidus (DI), be it from central or from nephrogenic origin, has to be differentiated from primary polydipsia. This differentiation is crucial since wrong treatment can have dangerous consequences. For decades, the "gold standard" for differential diagnosis has been the standard water deprivation test. However, this test has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 h and is cumbersome for patients. Also clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. Direct measurement of arginine vasopressin (AVP) upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay. Copeptin is secreted in equimolar ratio to AVP, mirroring AVP concentrations in the circulation. We have shown that copeptin, without prior fluid deprivation, identifies patients with nephrogenic DI. For the more difficult differentiation between central DI and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these 2 entities with a high diagnostic accuracy and is superior to the water deprivation test. However, it is important to note that close and regular sodium monitoring every 30 min during the hypertonic saline test is a prerequisite, which is not possible in all hospitals. Furthermore, side effects are common. Therefore, a nonosmotic stimulation test would be advantageous. Arginine significantly stimulates copeptin and therefore is a novel, so far unknown stimulus of this peptide. Consequently, infusion of arginine with subsequent copeptin measurement was shown to be an even simpler and better tolerated test, but head to head comparison is still lacking.

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Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study

Cited by 102 publications

References 24 publications

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

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

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia

Diabetes Insipidus: New Concepts for Diagnosis

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