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American Journal of Physiology. Renal... May 2021The association between diabetes insipidus (DI) and chronic dietary K deprivation is well known, but it remains uncertain how the disorder develops and whether it is... (Comparative Study)
Comparative Study
The association between diabetes insipidus (DI) and chronic dietary K deprivation is well known, but it remains uncertain how the disorder develops and whether it is influenced by the sexual dimorphism in K handling. Here, we determined the plasma K (P) threshold for DI in male and female mice and ascertained if DI is initiated by polydipsia or by a central or nephrogenic defect. C57BL6J mice were randomized to a control diet or to graded reductions in dietary K for 8 days, and kidney function and transporters involved in water balance were characterized. We found that male and female mice develop polyuria and secondary polydipsia. Altered water balance coincided with a decrease in aquaporin-2 (AQP2) phosphorylation and apical localization despite increased levels of the vasopressin surrogate marker copeptin. No change in the protein abundance of urea transporter-A1 was observed. The Na-K-2Cl cotransporter decreased only in males. Desmopressin treatment failed to reverse water diuresis in K-restricted mice. These findings indicate that even a small fall in P is associated with nephrogenic DI (NDI), coincident with the development of altered AQP2 regulation, implicating low P as a causal trigger of NDI. We found that P decreased more in females, and, consequently, females were more prone to develop NDI. Together, these data indicate that AQP2 regulation is disrupted by a small decrease in P and that the response is influenced by sexual dimorphism in K handling. These findings provide new insights into the mechanisms linking water and K balances and support defining the disorder as "potassium-dependent NDI." This study shows that aquaporin-2 regulation is disrupted by a small fall in plasma potassium levels and the response is influenced by sexual dimorphism in renal potassium handling. The findings provided new insights into the mechanisms by which water balance is altered in dietary potassium deficiency and support defining the disorder as "potassium-dependent nephrogenic diabetes insipidus."
Topics: Animals; Antidiuretic Agents; Aquaporin 2; Deamino Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; Disease Models, Animal; Drug Resistance; Female; Kidney; Male; Mice, Inbred C57BL; Phosphorylation; Potassium Deficiency; Potassium, Dietary; Risk Factors; Sex Characteristics; Water-Electrolyte Balance; Mice
PubMed: 33749322
DOI: 10.1152/ajprenal.00655.2020 -
The Netherlands Journal of Medicine Dec 2020The aetiology of hypotonic polyuria, after excluding solute diuresis, is one of primary polydipsia, central, or nephrogenic diabetes insipidus. Theoretically, these...
The aetiology of hypotonic polyuria, after excluding solute diuresis, is one of primary polydipsia, central, or nephrogenic diabetes insipidus. Theoretically, these disorders should be relatively easily distinguished based on history and the results of an indirect water deprivation test. Practically, however, there is a significant overlap in diagnostic evaluation, potentially leading to an erroneous diagnosis and deleterious management plan. The ability to measure a stimulated copeptin level, either with hypertonic saline or arginine infusion, has led to greater diagnostic accuracy.
Topics: Diabetes Insipidus; Diagnosis, Differential; Glycopeptides; Humans; Polyuria
PubMed: 33380527
DOI: No ID Found -
Journal of Human Genetics Oct 2021Wolfram syndrome (WFS) is characterized by deafness, diabetes mellitus, and diabetes insipidus along with optic atrophy. WFS has an autosomal recessive mode of...
BACKGROUND
Wolfram syndrome (WFS) is characterized by deafness, diabetes mellitus, and diabetes insipidus along with optic atrophy. WFS has an autosomal recessive mode of inheritance and is due to variants in WFS1 and CISD2.
METHODS
We evaluated the underlying molecular etiology of three affected members of a consanguineous family with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities via exome sequencing approach. We correlated clinical and imaging data with the genetic findings and their associated phenotypes.
RESULTS
We identified a homozygous missense variant p.(Asn1097Lys) in CDK13, a gene previously associated with autosomal dominant congenital heart defects, dysmorphic facial features, clinodactyly, gastrointestinal tract abnormalities, intellectual developmental disorder, and seizures with variable phenotypic features.
CONCLUSION
We report a homozygous variant in CDK13 and suggest that this gene causes an autosomal recessive disorder with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities.
Topics: Adolescent; Adult; Bicuspid Aortic Valve Disease; CDC2 Protein Kinase; Child; Child, Preschool; Consanguinity; Deafness; Diabetes Mellitus; Female; Gastrointestinal Tract; Genetic Predisposition to Disease; Hearing Loss; Homozygote; Humans; Infant; Male; Mutation, Missense; Optic Atrophy; Wolfram Syndrome; Young Adult
PubMed: 33879837
DOI: 10.1038/s10038-021-00922-0 -
Nephrologie & Therapeutique Dec 2022We describe here the case of a 54-year-old bipolar woman, followed in psychiatry and treated with lithium and a selective serotonin reuptake inhibitor (escitalopram) and...
We describe here the case of a 54-year-old bipolar woman, followed in psychiatry and treated with lithium and a selective serotonin reuptake inhibitor (escitalopram) and lamotrigine, presenting a lithium poisoning with an altered state of consciousness caused by a supposed mismanagement of her treatment. Lithium poisoning was suggested based on neurological clinical features, but the blood test brought out a lithium concentration within the therapeutic values at 1,2 mmol/L (N: 0,6-1,2 mmol/L). The classic biological complications related to lithium poisoning (hypercalcemia, diabetes insipidus) confirmed the diagnosis. The patient has been transferred to our nephrology department where she got two hemodialysis sessions conducting to clinical and biological improvement, confirming the diagnosis of lithium poisoning despite the normal blood levels. Later, she was transferred to the psychiatry department for follow-up and for treatment adjustment.
Topics: Female; Humans; Middle Aged; Lithium; Lithium Compounds; Hypercalcemia; Diabetes Insipidus; Diabetes Insipidus, Nephrogenic
PubMed: 36163235
DOI: 10.1016/j.nephro.2022.07.398 -
Cells Apr 2023Sex hormones play an important role in the regulation of water homeostasis, and we have previously shown that tamoxifen (TAM), a selective estrogen receptor modulator...
Sex hormones play an important role in the regulation of water homeostasis, and we have previously shown that tamoxifen (TAM), a selective estrogen receptor modulator (SERM), affects the regulation of aquaporin (AQP)-2. In this study, we investigated the effect of TAM on the expression and localization of AQP3 in collecting ducts using various animal, tissue, and cell models. The impact of TAM on AQP3 regulation was studied in rats subjected to 7 days of unilateral ureteral obstruction (UUO), with the rats fed a lithium-containing diet to induce nephrogenic diabetes insipidus (NDI), as well as in human precision-cut kidney slices (PCKS). Moreover, intracellular trafficking of AQP3 after TAM treatment was investigated in Madin-Darby Canine Kidney (MDCK) cells stably expressing AQP3. In all models, the expression of AQP3 was evaluated by Western blotting, immunohistochemistry and qPCR. TAM administration attenuated UUO-induced downregulation of AQP3 and affected the localization of AQP3 in both the UUO model and the lithium-induced NDI model. In parallel, TAM also affected the expression profile of other basolateral proteins, including AQP4 and Na/K-ATPase. In addition, TGF-β and TGF-β+TAM treatment affected the localization of AQP3 in stably transfected MDCK cells, and TAM partly attenuated the reduced AQP3 expression in TGF-β exposed human tissue slices. These findings suggest that TAM attenuates the downregulation of AQP3 in a UUO model and a lithium-induced NDI model and affects the intracellular localization in the collecting ducts.
Topics: Rats; Humans; Animals; Dogs; Aquaporin 3; Lithium; Tamoxifen; Kidney Tubules, Collecting; Kidney; Aquaporin 2; Diabetes Insipidus, Nephrogenic; Ureteral Obstruction
PubMed: 37190049
DOI: 10.3390/cells12081140 -
BMC Endocrine Disorders May 2022Novel coronavirus disease 2019 (COVID-19) mainly affects the lungs, but can involve several other organs. The diagnosis of acute and chronic sequelae is one of the...
BACKGROUND
Novel coronavirus disease 2019 (COVID-19) mainly affects the lungs, but can involve several other organs. The diagnosis of acute and chronic sequelae is one of the challenges of COVID-19. The current literature proposes that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may involve the hypothalamic-pituitary axis. In this case report, we present a unique case of new-onset central diabetes insipidus secondary to the COVID-19 disease in a 54-year-old woman.
CASE PRESENTATION
A 54-year-old woman presented with the history of excessive thirst, polyuria, and polydipsia, six weeks after being infected by COVID-19. Laboratory tests revealed low urine osmolarity and increased serum osmolarity, and the patient was diagnosed with central diabetes insipidus. After administration of nasal desmopressin, urinary osmolarity increased, and the patient's symptoms improved. However, to stabilize her condition, desmopressin treatment was required.
CONCLUSIONS
We reported a unique case of diabetes insipidus in a COVID-19 patient. Central diabetes insipidus may be included in clinical manifestations of the COVID-19, in case of new-onset polyuria and polydipsia following COVID-19 disease. Nevertheless, a causal relationship has not been established between the symptoms of the patient and the SARS-CoV-2 infection.
Topics: COVID-19; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Diabetes Mellitus; Female; Humans; Middle Aged; Polydipsia; Polyuria; SARS-CoV-2
PubMed: 35590312
DOI: 10.1186/s12902-022-01048-w -
PLoS Genetics Jul 2023Sleep disruptions are quite common in psychological disorders, but the underlying mechanism remains obscure. Wolfram syndrome 1 (WS1) is an autosomal recessive disease...
Sleep disruptions are quite common in psychological disorders, but the underlying mechanism remains obscure. Wolfram syndrome 1 (WS1) is an autosomal recessive disease mainly characterized by diabetes insipidus/mellitus, neurodegeneration and psychological disorders. It is caused by loss-of function mutations of the WOLFRAM SYNDROME 1 (WFS1) gene, which encodes an endoplasmic reticulum (ER)-resident transmembrane protein. Heterozygous mutation carriers do not develop WS1 but exhibit 26-fold higher risk of having psychological disorders. Since WS1 patients display sleep abnormalities, we aimed to explore the role of WFS1 in sleep regulation so as to help elucidate the cause of sleep disruptions in psychological disorders. We found in Drosophila that knocking down wfs1 in all neurons and wfs1 mutation lead to reduced sleep and dampened circadian rhythm. These phenotypes are mainly caused by lack of wfs1 in dopamine 2-like receptor (Dop2R) neurons which act to promote wake. Consistently, the influence of wfs1 on sleep is blocked or partially rescued by inhibiting or knocking down the rate-limiting enzyme of dopamine synthesis, suggesting that wfs1 modulates sleep via dopaminergic signaling. Knocking down wfs1 alters the excitability of Dop2R neurons, while genetic interactions reveal that lack of wfs1 reduces sleep via perturbation of ER-mediated calcium homeostasis. Taken together, we propose a role for wfs1 in modulating the activities of Dop2R neurons by impinging on intracellular calcium homeostasis, and this in turn influences sleep. These findings provide a potential mechanistic insight for pathogenesis of diseases associated with WFS1 mutations.
Topics: Humans; Wolfram Syndrome; Calcium; Receptors, Dopamine; Dopamine; Dopaminergic Neurons; Mutation; Sleep; Homeostasis
PubMed: 37399203
DOI: 10.1371/journal.pgen.1010827 -
European Journal of Endocrinology Jul 2019Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia.... (Review)
Review
Diabetes insipidus (DI), be it from central or nephrogenic origin, must be differentiated from secondary forms of hypotonic polyuria such as primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since decades, the gold standard for differentiation has been the water deprivation test, which has limitations leading to an overall unsatisfying diagnostic accuracy. Furthermore, it is cumbersome for patients with a long test duration. Clinical signs and symptoms and MRI characteristics overlap between patients with DI and primary polydipsia. The direct test including vasopressin (AVP) measurement upon osmotic stimulation was meant to overcome these limitations, but failed to enter clinical practice mainly due to technical constraints of the AVP assay. Copeptin is secreted in equimolar amount to AVP but can easily be measured with a sandwich immunoassay. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation and has led to a 'revival' of the direct test in the differential diagnosis of DI. We have shown that a baseline copeptin, without prior thirsting, unequivocally identifies patients with nephrogenic DI. In contrast, for the differentiation between central DI 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 superior to the water deprivation test. Close sodium monitoring during the test is a prerequisite. Further new test methods are currently evaluated and might provide an even simpler way of differential diagnosis in the future.
Topics: Awards and Prizes; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Glycopeptides; Humans; Polydipsia; Polyuria; Saline Solution, Hypertonic; Syndrome; Vasopressins
PubMed: 31067508
DOI: 10.1530/EJE-19-0163 -
Critical Care Medicine Dec 2019Vasopressin has achieved common usage for the treatment of catecholamine-requiring and catecholamine-resistant shock. Diabetes insipidus is a syndrome characterized by...
OBJECTIVES
Vasopressin has achieved common usage for the treatment of catecholamine-requiring and catecholamine-resistant shock. Diabetes insipidus is a syndrome characterized by excretion of abnormally large volumes of dilute urine. To date, very few reports of diabetes insipidus after discontinuation of vasopressin infusion have been published; the majority of previous reports describe neurosurgical patients. The purpose of the present study was to investigate the occurrence rate of diabetes insipidus after discontinuation of vasopressin infusion among patients treated with vasopressin infusion for shock.
DESIGN
Retrospective analysis of electronic health records of patients receiving continuous vasopressin infusion for the treatment of shock within a 5-year period (2012-2016).
SETTING
Medical, surgical, and cardiothoracic ICUs within one academic medical center.
PATIENTS
One-thousand eight-hundred ninety-six patients received vasopressin infusion for the treatment of shock.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
The occurrence rate of diabetes insipidus after discontinuation of vasopressin infusion was 1.53% among all patients. Sixteen of 29 patients with diabetes insipidus after discontinuation of vasopressin infusion had undergone cardiothoracic intervention, such as coronary artery bypass graft and valve replacement surgery, extracorporeal membrane oxygenation, and placement of ventricular assist devices. No neurosurgical patients were identified in our cohort. In a control group of patients receiving norepinephrine but not vasopressin infusion for treatment of shock, criteria for diabetes insipidus were observed in two of 1,320 subjects (0.15%).
CONCLUSIONS
Despite a paucity of published reports, diabetes insipidus after discontinuation of vasopressin infusion appears not to be a rare phenomenon, and is likely to be encountered by intensivists who regularly employ vasopressin for the treatment of vasoplegic shock. Previous reports consisted predominantly of neurosurgical patients. Our findings demonstrate the occurrence of diabetes insipidus after discontinuation of vasopressin infusion among patients with septic shock as well as vasoplegic shock after cardiothoracic intervention. The mechanism of diabetes insipidus after discontinuation of vasopressin infusion remains to be elucidated but may involve transient downregulation of V2 receptors induced by exposure to supraphysiological doses of vasopressin.
Topics: Adult; Child, Preschool; Diabetes Insipidus; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies; Shock; Vasopressins; Withholding Treatment; Young Adult
PubMed: 31567344
DOI: 10.1097/CCM.0000000000004045 -
Journal of the American Society of... Jul 2016
Topics: Aquaporin 2; Aquaporins; Diabetes Insipidus, Nephrogenic; Humans; Mutation; Receptors, Vasopressin; Water
PubMed: 26712528
DOI: 10.1681/ASN.2015111223