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Advances in Experimental Medicine and... 2023Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI)...
Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understanding the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI). This is followed by a discussion of regulatory mechanisms underlying CDI and NDI, with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R) and the water channel molecule, aquaporin 2 (AQP2). The clinical manifestation, diagnosis, and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.
Topics: Animals; Aquaporin 2; Diabetes Insipidus, Nephrogenic; Diabetes Insipidus; Aquaporins; Kidney; Water; Mutation; Receptors, Vasopressin; Diabetes Mellitus
PubMed: 36717500
DOI: 10.1007/978-981-19-7415-1_18 -
Endocrinology and Metabolism Clinics of... Jun 2017Diabetes insipidus is a disease characterized by polyuria and polydipsia due to inadequate release of arginine vasopressin from the posterior pituitary gland... (Review)
Review
Diabetes insipidus is a disease characterized by polyuria and polydipsia due to inadequate release of arginine vasopressin from the posterior pituitary gland (neurohypophyseal diabetes insipidus) or due to arginine vasopressin insensitivity by the renal distal tubule, leading to a deficiency in tubular water reabsorption (nephrogenic diabetes insipidus). This article reviews the genetics of diabetes insipidus in the context of its diagnosis, clinical presentation, and therapy.
Topics: Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Humans; Pituitary Gland, Posterior
PubMed: 28476225
DOI: 10.1016/j.ecl.2017.01.002 -
Vitamins and Hormones 2020V2 vasopressin receptor (V2R) is a member of the G protein-coupled receptor (GPCR) family in which many disease-causing mutations have been identified and thus generated... (Review)
Review
V2 vasopressin receptor (V2R) is a member of the G protein-coupled receptor (GPCR) family in which many disease-causing mutations have been identified and thus generated much interest. Loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI) whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The mechanisms underlying a V2R loss-of-function can be theoretically classified as either protein expression, localization (ER retention) or functional disorders. Functional analyses have revealed however that these mechanisms are likely to be complex. Strikingly, V2R mutations at the same site can result in opposite phenotypes, e.g., R137H and R137L/C cause NDI and NSIAD, respectively. These findings support the notion that the constitutive activation of GPCRs might be often associated with their instability and denaturation. Thus, functional analysis of disease-causing V2R mutations may not only reveal potential new treatment strategies using pharmacochaperones for NDI and inverse agonists for NSIAD, but also provide a greater understanding of the physiological functions of GPCRs and highlight the new paradigms, i.e., biased agonism and protean agonism.
Topics: Diabetes Insipidus, Nephrogenic; Humans; Mutation; Receptors, Vasopressin
PubMed: 32138955
DOI: 10.1016/bs.vh.2019.08.012 -
Journal of Pain & Palliative Care... 2018The authors report a case of diabetes insipidus (DI) associated with a ketamine infusion. A 42-year-old Asian man underwent an exploratory laparotomy and splenectomy who...
The authors report a case of diabetes insipidus (DI) associated with a ketamine infusion. A 42-year-old Asian man underwent an exploratory laparotomy and splenectomy who was admitted to the surgical intensive care unit (ICU) for postoperative management. Pain control was attempted with escalating dose of opioids but was inadequate, prompting the addition of a ketamine infusion. Shortly after initiation, a massive rise in urine output ensued in addition to a change in his urine electrolyte studies, leading to the diagnosis of drug-induced diabetes insipidus. Ketamine was discontinued, and treatment with subcutaneous desmopressin was initiated. Treatment was continued for a total of 5 days, which resulted in a resolution of his DI. This report suggests that the patient likely experienced a medication-induced DI, which was successfully resolved through proper identification of the causative agent, removal, and subsequent treatment with desmopressin. Causality assessment between ketamine and DI was determined using the Naranjo Adverse Drug Reaction Probability Scale-a total score of 7 was achieved and thus identified the adverse drug reaction as probable. Clinicians should be aware of the possibility that ketamine may be contributory in a patient with unexplained DI.
Topics: Adult; Analgesics; Analgesics, Opioid; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Ketamine; Laparotomy; Male; Pain, Postoperative; Splenectomy
PubMed: 30702377
DOI: 10.1080/15360288.2018.1508111 -
Endocrinology and Metabolism Clinics of... Sep 2019Diagnosis of lymphocytic hypophysitis occurring in the peripartum period is based on clinical and neuroradiological data and does not require a biopsy. Its course is... (Review)
Review
Diagnosis of lymphocytic hypophysitis occurring in the peripartum period is based on clinical and neuroradiological data and does not require a biopsy. Its course is generally spontaneously favorable in terms of mass effect but may require the administration of corticosteroids or even transsphenoidal resection. The course of pituitary deficiencies is highly variable; some cases recover over time, whereas others persist indefinitely. Sheehan syndrome is very rare in developed countries. Because agalactia and amenorrhea are often neglected, the diagnosis is generally delayed. Diabetes insipidus occurring in late pregnancy is caused by the increased placental production of vasopressinase and disappears after delivery.
Topics: Diabetes Insipidus; Female; Humans; Hypopituitarism; Pituitary Diseases; Pregnancy; Pregnancy Complications
PubMed: 31345525
DOI: 10.1016/j.ecl.2019.05.005 -
Handbook of Clinical Neurology 2021The hormone arginine vasopressin (AVP) is a nonapeptide synthesized by hypothalamic magnocellular nuclei and secreted from the posterior pituitary into the bloodstream.... (Review)
Review
The hormone arginine vasopressin (AVP) is a nonapeptide synthesized by hypothalamic magnocellular nuclei and secreted from the posterior pituitary into the bloodstream. It binds to AVP receptor 2 in the kidney to promote the insertion of aquaporin channels (AQP2) and antidiuretic responses. AVP secretion deficits produce central diabetes insipidus (CDI), while renal insensitivity to the antidiuretic effect of AVP causes nephrogenic diabetes insipidus (NDI). Hereditary and acquired forms of CDI and NDI generate hypotonic polyuria, polydipsia, hyperosmolality, and hypernatremia. The AVP mutant (Brattleboro) rat is the principal animal model of hereditary CDI, while neurohypophysectomy, pituitary stalk compression, hypophysectomy, and mediobasal hypothalamic lesions produce acquired CDI. In animals, hereditary NDI is mainly caused by mutations in AVP2R or AQP2 genes, while acquired NDI is most frequently induced by lithium. We report here on the determinants of the intake and excretion of water and mineral salts and on the different types of DI in humans. We then describe the hydromineral characteristics of these animal models and the responses observed after administration of hypertonic NaCl or when they are fed with low-sodium diets. Finally, we report on the effects of drugs such as AVP analogues and/or oxytocin, another neuropeptide that increases sodium excretion in animal models and humans with CDI, and sildenafil, a compound that increases the expression and function of AQP2 channels in animal models and humans with NDI.
Topics: Animals; Aquaporin 2; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic; Diabetes Mellitus; Humans; Models, Animal; Rats; Rats, Brattleboro
PubMed: 34238463
DOI: 10.1016/B978-0-12-820683-6.00020-8 -
Frontiers in Endocrinology 2023Copeptin is cleaved from the same precursor as arginine vasopressin and is released in equimolar amounts with arginine vasopressin from the posterior pituitary in... (Review)
Review
Copeptin is cleaved from the same precursor as arginine vasopressin and is released in equimolar amounts with arginine vasopressin from the posterior pituitary in response to the same stimuli. Its level of stability in the blood, quick and simple analysis, and ease of automation make it much easier to analyze than arginine vasopressin, thereby offering a suitable alternative to measuring arginine vasopressin in endocrine disorders. Research has demonstrated the suitability of copeptin in adults for the differentiation of arginine vasopressin resistance and arginine vasopressin deficiency from primary polydipsia, in addition to the early identification of arginine vasopressin deficiency following pituitary surgery; however, further research is still required in the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) and the pediatric population.
Topics: Child; Adult; Humans; Diabetes Insipidus, Neurogenic; Glycopeptides; Arginine Vasopressin; Arginine
PubMed: 37859988
DOI: 10.3389/fendo.2023.1230045 -
Molecular and Cellular Endocrinology Jan 2023Nephrogenic diabetes insipidus is defined as an inability to concentrate urine due to a complete or partial alteration of the renal tubular response to arginine... (Review)
Review
Nephrogenic diabetes insipidus is defined as an inability to concentrate urine due to a complete or partial alteration of the renal tubular response to arginine vasopressin hormone, resulting in excessive diluted urine excretion. Hereditary forms are caused by molecular defects in the genes encoding either of the two main renal effectors of the arginine vasopressin pathway: the AVPR2 gene, which encodes for the type 2 vasopressin receptor, or the AQP2 gene, which encodes for the water channel aquaporin-2. About 90% of cases of nephrogenic diabetes insipidus result from loss-of-function variants in the AVPR2 gene, which are inherited in a X-linked recessive manner. The remaining 10% of cases result from loss-of-function variants in the AQP2 gene, which can be inherited in either a recessive or a dominant manner. The main symptoms of the disease are polyuria, chronic dehydration and hypernatremia. These symptoms usually occur in the first year of life, although some patients present later. Diagnosis is based on abnormal response in urinary osmolality after water restriction and/or administration of exogenous vasopressin. Treatment involves ensuring adequate water intake on demand, possibly combined with thiazide diuretics, non-steroidal anti-inflammatory drugs, and a low-salt and protein diet. In this review, we provide an update on current understanding of the molecular basis of inherited nephrogenic insipidus diabetes.
Topics: Humans; Aquaporin 2; Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; Mutation; Receptors, Vasopressin
PubMed: 36460218
DOI: 10.1016/j.mce.2022.111825 -
Best Practice & Research. Clinical... Mar 2016Diabetes insipidus (DI) in pregnancy is a heterogeneous syndrome, most classically presenting with polyuria and polydipsia that can complicate approximately 1 in 30,000... (Review)
Review
Diabetes insipidus (DI) in pregnancy is a heterogeneous syndrome, most classically presenting with polyuria and polydipsia that can complicate approximately 1 in 30,000 pregnancies. The presentation can involve exacerbation of central or nephrogenic DI during pregnancy, which may have been either overt or subclinical prior to pregnancy. Women without preexisting DI can also be affected by the actions of placental vasopressinase which increases in activity between the 4th and 38th weeks of gestation, leading to accelerated metabolism of AVP and causing a transient form of DI of pregnancy. This type of DI may be associated with certain complications during pregnancy and delivery, such as preeclampsia. Management of DI of pregnancy depends on the pathophysiology of the disease; forms of DI that lack AVP can be treated with desmopressin (DDAVP), while forms of DI that involve resistance to AVP require evaluation of the underlying causes.
Topics: Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Pregnancy; Pregnancy Complications
PubMed: 27156766
DOI: 10.1016/j.beem.2016.02.005 -
Journal of Pediatric Endocrinology &... Jan 2016Diabetes insipidus (DI) is one of the common disorders affecting sodium and water homeostasis, and results when ADH is either inadequately produced, or unable to... (Review)
Review
Diabetes insipidus (DI) is one of the common disorders affecting sodium and water homeostasis, and results when ADH is either inadequately produced, or unable to negotiate its actions on the renal collecting tubules through aquaporins. The diagnostic algorithm starts with exclusion of other causes of polyuria and establishing low urine osmolality in the presence of high serum osmolality. In this paper, we have reviewed the diagnosis, etiology and management of DI in children, with special emphasis on recent advances in the field.
Topics: Child; Diabetes Insipidus; Humans
PubMed: 26353165
DOI: 10.1515/jpem-2014-0518