Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2

Powlson, Andrew S; Challis, Benjamin; Halsall, David; Schoenmakers, Erik; Gurnell, Mark

doi:10.1111/cen.13011

Cited by 20 publications

(15 citation statements)

References 38 publications

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“…In affected male and female patients, the continuous activation of the vasopressin receptor leads to AVP‐independent antidiureses. Consecutively, AVP/copeptin levels are low or suppressed in these patients . Management of this disorder includes fluid restriction and avoidance of potential episodes of fluid overload.…”

Section: The Role Of Copeptin In the Diagnosis Of Siadmentioning

confidence: 99%

Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis

Refardt

Winzeler

2019

Clinical Endocrinology

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Clinical Endocrinology. 2019;91:22-32. wileyonlinelibrary.com/journal/cen 1 | INTRODUC TI ON Arginine vasopressin (AVP) is the main regulating hormone of body fluid homeostasis. It is secreted from the posterior pituitary upon osmotic or nonosmotic stimuli, with the main osmotic stimulus being increased plasma osmolality and the main nonosmotic stimulus being hypovolaemia and promotes water reabsorption via V2 receptors in the kidney, thereby normalizing hypertonicity and vasomotor tone. Disorders of body fluid homeostasis are common and can be divided into hyper-and hypoosmolar circumstances: the classical AbstractCopeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for copeptin are similar to AVP, that is an increase in osmolality and a decrease in arterial blood volume and pressure. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation.Copeptin has, therefore, been evaluated as diagnostic biomarker in vasopressin-dependent disorders of body fluid homeostasis. Disorders of body fluid homeostasis are common and can be divided into hyper-and hypoosmolar circumstances: the classical hyperosmolar disorder is diabetes insipidus, while the most common hypoosmolar disorder is the syndrome of inappropriate antidiuresis (SIAD). Copeptin measurement has led to a "revival" of the direct test in the differential diagnosis of diabetes insipidus. Baseline copeptin levels, without prior thirsting, unequivocally identify patients with nephrogenic diabetes insipidus. In contrast, for the difficult differentiation between central diabetes insipidus and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is clearly superior to the classical water deprivation test. On the contrary, in the SIAD, copeptin measurement is of only little diagnostic value. Copeptin levels widely overlap in patients with hyponatraemia and emphasize the heterogeneity of the disease. Additionally, a variety of factors lead to unspecific copeptin elevations in the acute setting further complicating its interpretation. The broad use of copeptin as diagnostic marker in hyponatraemia and specifically to detect cancer-related disease in SIADH patients can, therefore, not be recommended. K E Y W O R D Scopeptin, diabetes insipidus, diagnosis, hypernatremia, hyponatraemia, primary polydipsia, SIAD This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Section: The Role Of Copeptin In the Diagnosis Of Siadmentioning

confidence: 99%

Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis

Refardt

Winzeler

2019

Clinical Endocrinology

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“…For example, missense mutations in AVPR2 encoding the arginine vasopressin receptor 2 were shown to cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD), a mirror phenotype of nephrogenic diabetes insipidus due to loss‐of‐function mutations in AVPR2 . NSIAD is a subtype of syndrome of inappropriate antidiuresis (SIAD), which is characterized by euvolaemic hyponatraemia due to diminished free water excretion in the renal collecting ducts . While most cases of SIAD are ascribed to excessive secretion of arginine vasopressin (AVP) from the pituitary, NSIAD is characterized by hyponatraemia with relatively low blood levels of AVP .…”

Section: Endocrine Syndromes Caused By Germline Gpcr Activating Mutatmentioning

confidence: 99%

“…NSIAD is a subtype of syndrome of inappropriate antidiuresis (SIAD), which is characterized by euvolaemic hyponatraemia due to diminished free water excretion in the renal collecting ducts . While most cases of SIAD are ascribed to excessive secretion of arginine vasopressin (AVP) from the pituitary, NSIAD is characterized by hyponatraemia with relatively low blood levels of AVP . This phenotype of NSIAD results from increased constitutive activity of AVPR2 in the renal collecting ducts.…”

Section: Endocrine Syndromes Caused By Germline Gpcr Activating Mutatmentioning

confidence: 99%

“…This phenotype of NSIAD results from increased constitutive activity of AVPR2 in the renal collecting ducts. Patients with NSIAD present with several neurological features, such as loss of consciousness and seizure, reflecting hyponatraemia …”

Section: Endocrine Syndromes Caused By Germline Gpcr Activating Mutatmentioning

confidence: 99%

“…First, genetic information is useful to confirm the clinical diagnosis. For example, mutation analysis of AVPR2 helps to identify patients with NSIAD among individuals with hyponatraemia, which is a relatively common multifactorial condition . Molecular diagnosis may reduce the necessity of further laboratory examinations such as water load test.…”

Section: Molecular Diagnosis Of Patients With Gpcr Gain‐of‐function Mmentioning

confidence: 99%

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Gain‐of‐function mutations in G‐protein–coupled receptor genes associated with human endocrine disorders

Fukami

Suzuki

Igarashi

et al. 2017

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SummaryThe human genome encodes more than 700 G-protein-coupled receptors (GPCRs), many of which are involved in hormone secretion. To date, more than 100 gain-offunction (activating) mutations in at least ten genes for GPCRs, in addition to several loss-of-function mutations, have been implicated in human endocrine disorders.Previously reported gain-of-function GPCR mutations comprise various missense substitutions, frameshift mutations, intragenic inframe deletions and copy-number gains.

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Three cases in which drug‐induced hyponatremia was improved by replacing carbamazepine with lacosamide

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et al. 2020

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Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2

Abstract: NSIAD should be considered in young patients with unexplained hyponatraemia. A water load test with AVP measurement is a potentially informative investigation, while AVPR2 sequencing provides a definitive molecular genetic diagnosis and a rationale for long-term fluid restriction.

Cited by 20 publications

References 38 publications

Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis

Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis

Gain‐of‐function mutations in G‐protein–coupled receptor genes associated with human endocrine disorders

Three cases in which drug‐induced hyponatremia was improved by replacing carbamazepine with lacosamide

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