2,177 results on '"Nephrogenic diabetes insipidus"'
Search Results
2. Autosomal dominant nephrogenic diabetes insipidus in one family caused by a novel AQP2 mutation.
- Author
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Huang, Hou‐Xuan, Sullivan, Monika, Zayas Borges, Paola, and Kennedy, Sabina
- Subjects
- *
GENETIC testing , *EOSINOPHILIC esophagitis , *PEDIATRIC nephrology , *DIABETES in children , *HYPERNATREMIA - Abstract
A 9‐month‐old male presented with vomiting and dehydration with mild hypernatremia in the context of failure to thrive. He was later diagnosed with nephrogenic diabetes insipidus (NDI) during this hospitalisation and was also found to have eosinophilic esophagitis (EoE). He has since been growing well after EoE and NDI were properly managed. Molecular genetic testing revealed an unreported deletion in AQP2 which was deemed pathogenic and of autosomal dominant inheritance when correlated with his clinical findings and family history. This case report describes the clinical course of this patient in comparison to his family members and reviews current literature on autosomal dominant NDI caused by AQP2 mutations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Acute lymphoblastic leukemia with nephrogenic diabetes insipidus as the first symptom: a case report.
- Author
-
Qu, Ning and Zhu, Hongtao
- Subjects
- *
EXTRAMEDULLARY diseases , *LYMPHOBLASTIC leukemia , *SYMPTOMS , *ASIANS , *ACUTE leukemia , *DIABETES insipidus - Abstract
Background: Acute lymphoblastic leukemia is the most common pediatric malignancy, characterized by fever, anemia, hemorrhage, and symptoms brought on by blasts infiltrating organs. Case presentation: This is a case report of a 9-year-old Asian patient with acute lymphoblastic leukemia who presented with polyuria alone as a presenting feature without any other clinical manifestation; primary renal disease or inherited metabolic disease was highly suspected. However, the water deprivation test and water deprivation pressurization test suggested nephrogenic diabetes insipidus, and the renal biopsy displayed diffuse lymphocytic infiltration in the renal interstitium. Bone marrow aspiration was performed immediately, and a comprehensive diagnosis of B-lymphoblastic leukemia was finally made. Conclusions: Renal infiltration with leukemic blasts mostly remains asymptomatic, but our case suggests that it can present with nephrogenic diabetes insipidus. This case fully demonstrates that the presentation of extramedullary infiltration in acute lymphoblastic leukemia is varied. When the patient has renal diabetes insipidus as the first symptom, the possibility of hematological tumor infiltration should be considered when finding the cause, and timely bone marrow cytology should be performed. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Lithium-induced apoptotic cell death is not accompanied by a noticeable inflammatory response in the kidney.
- Author
-
Baranovskaya, Irina, Volk, Kevin, Alexander, Sati, Abais-Battad, Justine, and Mamenko, Mykola
- Subjects
DIABETES insipidus ,CELL death ,LITHIUM carbonate ,FLOW cytometry ,CASPASES - Abstract
Lithium (Li
+ ) therapy is a valuable tool in psychiatric practice that remains underutilized due to safety concerns. Excessive plasma Li+ levels are nephrotoxic and can trigger a local immune response. Our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+ -induced adverse effects in the kidneys of C57BL/6NJ mice placed on a 0.3% lithium carbonate diet for 28 days. We combined histochemical techniques, immunoblotting, flow cytometry, qPCR and proteome profiler arrays to characterize renal tissue damage, infiltrating immune cells and cytokine markers, activation of pyroptotic and apoptotic cascades in the kidneys of mice receiving Li+ -containing and regular diets. We found that biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinaseassociated lipocalin, NGAL, were elevated in the renal tissue of Li+ -treated mice when compared to controls. This correlated with increased interstitial fibrosis in Li+ -treated mice. Administration of Li+ did not activate the proinflammatory NLRP3 inflammasome cascade but promoted apoptosis in the renal tissue. The TUNEL-positive signal and levels of pro-apoptotic proteins, Bax, cleaved caspase-3, and caspase-8, were elevated in the kidneys of Li+ - treated mice. We observed a significantly higher abundance of CD93, CCL21, and fractalkine, accumulation of F4.80+ macrophages with reduced M1/ M2 polarization ratio and decreased CD4+ levels in the renal tissue of Li+ - treated mice when compared to controls. Therefore, after 28 days of treatment, Li+ -induced insult to the kidney manifests in facilitated apoptotic cell death without an evident pro-inflammatory response. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
5. Effects of YM087 and VPA985 on the T237M mutant receptor functionality in nephrogenic diabetes insipidus.
- Author
-
Avcu, Elif Merve, Erdem Tuncdemir, Beril, and Saglar Ozer, Emel
- Subjects
- *
MOLECULAR chaperones , *DIABETES insipidus , *VASOPRESSIN , *FLOW cytometry , *QUALITY control - Abstract
Mutations detected in the
AVPR2 gene (arginine vasopressin type 2 receptor) are known to cause nephrogenic diabetes insipidus (NDI). Several pharmacological chaperones (PCs) target misfolded AVPR2 proteins and rescue them from the quality control system of the cell. In this study, we investigated the effect of YM087 and VPA985, which are PCs, on T273M-AVPR2 mutant that are known to cause NDI.The total and cell surface expressions of T273M in COS-1 cells were measured by sandwich ELISA and flow cytometry after the cells were treated with YM087 and VPA985 separately. In addition, the cAMP accumulation assay was performed.It was observed that VPA985 treatment significantly increased the cell surface expression and slightly increased the maximum cAMP response of T273M. Both YM087 and VPA985 decreased the ligand concentrations which were responsible for making half of the maximum response of the T273M mutant receptor.PCs have different potential effects on different AVPR2 mutants. Therefore, studying the effectiveness of PCs in rescuing AVPR2 mutants and making them functional again may contribute to the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
6. 'Aquaporin‐omics': mechanisms of aquaporin‐2 loss in polyuric disorders.
- Author
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Mak, Angela, Sung, Chih‐Chien, Pisitkun, Trairak, Khositseth, Sookkasem, and Knepper, Mark A.
- Subjects
- *
AQUAPORINS , *ANIMAL models in research , *PROTEOMICS , *INFLAMMATION , *PATHOLOGY - Abstract
Animal models of a variety of acquired nephrogenic diabetes insipidus (NDI) disorders have identified a common feature: all such models are associated with the loss of aquaporin‐2 (AQP2) from collecting duct principal cells, explaining the associated polyuria. To discover mechanisms of AQP2 loss, previous investigators have carried out either transcriptomics (lithium‐induced NDI, unilateral ureteral obstruction, endotoxin‐induced NDI) or proteomics (hypokalaemia‐associated NDI, hypercalcaemia‐associated NDI, bilateral ureteral obstruction), yielding contrasting views. Here, to address whether there may be common mechanisms underlying loss of AQP2 in acquired NDI disorders, we have used bioinformatic data integration techniques to combine information from all transcriptomic and proteomic data sets. The analysis reveals roles for autophagy/apoptosis, oxidative stress and inflammatory signalling as key elements of the mechanism that results in loss of AQP2. These processes can cause AQP2 loss through the combined effects of repression of Aqp2 gene transcription, generalized translational repression, and increased autophagic degradation of proteins including AQP2. Two possible types of stress‐sensor proteins, namely death receptors and stress‐sensitive protein kinases of the EIF2AK family, are discussed as potential triggers for signalling processes that result in loss of AQP2. Key points: Prior studies have shown in a variety of animal models of acquired nephrogenic diabetes insipidus (NDI) that loss of the aquaporin‐2 (AQP2) protein is a common feature.Investigations of acquired NDI using transcriptomics (RNA‐seq) and proteomics (protein mass spectrometry) have led to differing conclusions regarding mechanisms of AQP2 loss.Bioinformatic integration of transcriptomic and proteomic data from these prior studies now reveals that acquired NDI models map to three core processes: oxidative stress, apoptosis/autophagy and inflammatory signalling.These processes cause loss of AQP2 through translational repression, accelerated degradation of proteins, and transcriptional repression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. Acute lymphoblastic leukemia with nephrogenic diabetes insipidus as the first symptom: a case report
- Author
-
Ning Qu and Hongtao Zhu
- Subjects
Acute lymphoblastic leukemia ,Nephrogenic diabetes insipidus ,Children ,Case report ,Medicine - Abstract
Abstract Background Acute lymphoblastic leukemia is the most common pediatric malignancy, characterized by fever, anemia, hemorrhage, and symptoms brought on by blasts infiltrating organs. Case presentation This is a case report of a 9-year-old Asian patient with acute lymphoblastic leukemia who presented with polyuria alone as a presenting feature without any other clinical manifestation; primary renal disease or inherited metabolic disease was highly suspected. However, the water deprivation test and water deprivation pressurization test suggested nephrogenic diabetes insipidus, and the renal biopsy displayed diffuse lymphocytic infiltration in the renal interstitium. Bone marrow aspiration was performed immediately, and a comprehensive diagnosis of B-lymphoblastic leukemia was finally made. Conclusions Renal infiltration with leukemic blasts mostly remains asymptomatic, but our case suggests that it can present with nephrogenic diabetes insipidus. This case fully demonstrates that the presentation of extramedullary infiltration in acute lymphoblastic leukemia is varied. When the patient has renal diabetes insipidus as the first symptom, the possibility of hematological tumor infiltration should be considered when finding the cause, and timely bone marrow cytology should be performed.
- Published
- 2024
- Full Text
- View/download PDF
8. Goodbye Diabetes Insipidus
- Author
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Bonneville, Jean-François and Bonneville, Jean-François
- Published
- 2024
- Full Text
- View/download PDF
9. National Registry of Rare Kidney Diseases (RaDaR)
- Published
- 2023
10. Remission of nephrogenic diabetes insipidus (arginine vasopressin resistance): description of a rare clinical case
- Author
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R. M. Guseinova, E. A. Pigarova, and L. K. Dzeranova
- Subjects
nephrogenic diabetes insipidus ,desmopressin ,diuresis ,kidney ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Nephrogenic diabetes insipidus is a heterogeneous disease in the etiopathogenesis of which are involved acquired and congenital factors. In this case, the kidneys do not respond to vasopressin and continue to produce large concentrated volumes of urine. Distinctive features in the pathology of central genesis are the fact of trauma, brain tumor with involvement of pituitary gland, response to intranasal vasopressin in the form of decreased diuresis.For diagnosis it is important to perform a series of differential diagnostic tests.In this article we present a unique clinical case of a patient with a long-term course of diabetes insipidus with the development a spectrum of comorbid conditions, metabolic disorders, required kidney transplantation.
- Published
- 2024
- Full Text
- View/download PDF
11. The β3‐AR agonist BRL37344 ameliorates the main symptoms of X‐linked nephrogenic diabetes insipidus in the mouse model of the disease.
- Author
-
Milano, Serena, Saponara, Ilenia, Gerbino, Andrea, Carmosino, Monica, Svelto, Maria, and Procino, Giuseppe
- Subjects
DIABETES insipidus ,LABORATORY mice ,KIDNEY tubules ,ANIMAL disease models ,CONTROLLED release preparations ,DRINKING (Physiology) - Abstract
X‐linked nephrogenic diabetes insipidus (X‐NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type‐2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP‐intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3‐adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3‐AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X‐NDI. Here we demonstrate that the β3‐AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X‐NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow‐release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X‐NDI mice. Taken together, these data suggest that human β3‐AR agonists might represent an effective possible treatment strategy for X‐NDI. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
12. Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population.
- Author
-
Ghasemi, Saeed, Mojbafan, Marzieh, Talebi, Saeed, Hooman, Nakysa, and Hoseini, Rozita
- Subjects
- *
DIABETES insipidus , *IRANIANS , *MEDICAL genetics , *PEOPLE with diabetes , *X chromosome , *MEDICAL genomics - Abstract
Introduction: Nephrogenic diabetes insipidus (NDI) is a rare genetic disease that causes water imbalance. The kidneys play a crucial role in regulating body fluids by controlling water balance through urine excretion. This highlights their essential function in managing the body's water levels, but individuals with NDI may have excess urine production (polyuria), that leads to excessive thirst (polydipsia). Untreated affected individuals may exhibit poor feeding and failure to thrive. This disease is caused by mutations in the AVPR2 and the AQP2 genes which have the X‐linked and autosomal recessive/dominant inheritance, respectively. Both of these genes are expressed in the kidney. Methods: Twelve Iranian patients from 10 consanguineous families were studied in this project. DNA was extracted from the whole blood samples of the patients and their parents. All coding exons and exon‐intron boundaries of the AVPR2 and AQP2 genes were sequenced in the affected individuals, and the identified variants were investigated in the parents. All variants were analyzed according to the ACMG (American College of Medical Genetics and Genomics) guidelines. Results: In this study, 6 different mutations were identified in the patients, including 5 in the AQP2 gene (c.439G>A, c.538G>A, c.140C>T, c.450T>A, and the novel c.668T>C) and 1 in the AVPR2 gene (c.337C>T) in the present study. Discussion: As expected, all the detected mutations in this study were missense. According to the ACMG guideline, the identified mutations were categorized as pathogenic or likely pathogenic. Unlike previous studies which showed more than 90% of mutations were in the AVPR2 gene, and only less than 10% of the mutations were in the AQP2 gene, it was found that more than 90% of our identified mutations located in the AQP2 gene, and only one mutation was observed in the AVPR2 gene, which seems it may be a result of the high rate of consanguineous marriages in the Iranian population. We observed genotype‐phenotype correlation in some of our affected individuals, and some of the mutations were observed in unrelated families from same ethnicity which could be suggestive of a founder mutation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
13. Lithium-induced apoptotic cell death is not accompanied by a noticeable inflammatory response in the kidney
- Author
-
Irina Baranovskaya, Kevin Volk, Sati Alexander, Justine Abais-Battad, and Mykola Mamenko
- Subjects
anti-inflammatory ,apoptosis ,lithium ,nephrogenic diabetes insipidus ,renal damage ,macrophage polarization ,Physiology ,QP1-981 - Abstract
Lithium (Li+) therapy is a valuable tool in psychiatric practice that remains underutilized due to safety concerns. Excessive plasma Li+ levels are nephrotoxic and can trigger a local immune response. Our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+-induced adverse effects in the kidneys of C57BL/6NJ mice placed on a 0.3% lithium carbonate diet for 28 days. We combined histochemical techniques, immunoblotting, flow cytometry, qPCR and proteome profiler arrays to characterize renal tissue damage, infiltrating immune cells and cytokine markers, activation of pyroptotic and apoptotic cascades in the kidneys of mice receiving Li+-containing and regular diets. We found that biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinase-associated lipocalin, NGAL, were elevated in the renal tissue of Li+-treated mice when compared to controls. This correlated with increased interstitial fibrosis in Li+-treated mice. Administration of Li+ did not activate the pro-inflammatory NLRP3 inflammasome cascade but promoted apoptosis in the renal tissue. The TUNEL-positive signal and levels of pro-apoptotic proteins, Bax, cleaved caspase-3, and caspase-8, were elevated in the kidneys of Li+-treated mice. We observed a significantly higher abundance of CD93, CCL21, and fractalkine, accumulation of F4.80+ macrophages with reduced M1/M2 polarization ratio and decreased CD4+ levels in the renal tissue of Li+-treated mice when compared to controls. Therefore, after 28 days of treatment, Li+-induced insult to the kidney manifests in facilitated apoptotic cell death without an evident pro-inflammatory response.
- Published
- 2024
- Full Text
- View/download PDF
14. Clinical manifestations and renal pathology of ethylene glycol
- Author
-
Taira, Shogo, Tamayose, Shiori, Kikumura, Tasuku, and Nishihira, Morikuni
- Published
- 2024
- Full Text
- View/download PDF
15. Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus
- Author
-
Lukáš Strych, Monika Černá, Markéta Hejnalová, Tomáš Zavoral, Pavla Komrsková, Jitka Tejcová, Ibrahim Bitar, Eva Sládková, Josef Sýkora, and Ivan Šubrt
- Subjects
Long-read sequencing ,PacBio ,Breakpoint analysis ,AVPR2 deletion ,Nephrogenic diabetes insipidus ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS). Methods A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females. Results By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands´ mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR. Conclusions Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.
- Published
- 2024
- Full Text
- View/download PDF
16. Nephrogenic Diabetes Insipidus During Prolonged Sevoflurane Sedation in the ICU: a Retrospective Analysis
- Published
- 2023
17. First report on female monozygotic twins discordant for congenital nephrogenic diabetes insipidus.
- Author
-
Chen, Xiang, Yun, Libing, Long, Yang, Sun, Yuxia, and Chen, Tao
- Abstract
Ninety percent of congenital nephrogenic diabetes insipidus (NDI) are X‐linked inherited and are caused by mutations in the vasopressin type 2 receptor gene (AVPR2). Most affected individuals are males. Only sporadic female cases have been reported. Here, we first reported a female monozygotic twin with discordant phenotypes for NDI carrying a missense variant c.845T>C (p.Leu282Pro) in exon 4 of AVPR2. Intracellular cAMP concentrations in COS7 cells transfected with AVPR2‐L282P were significantly decreased by about 60% compared with those in wild‐type AVPR2 plasmid transfected cells, suggesting this variation was pathogenic. The X‐inactivation pattern was investigated in peripheral leukocytes and urine sediments in both the unaffected and affected pair. Results showed that the affected pair had a skewed X chromosome inactivation (XCI) pattern in urine sediments and a random XCI pattern in leukocytes, while the unaffected pair showed a random XCI pattern both in leukocytes and urine sediments. This was the first report of monozygotic twins who developed different phenotypes of NDI. Our study suggested that the development of NDI symptoms is more closely associated with the XCI pattern in urine sediments compared with the XCI pattern in peripheral leukocytes. Analysis of XCI in peripheral leukocytes may not be enough to explore possible mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. Urine concentration impairment in sickle cell anemia: genuine nephrogenic diabetes insipidus or osmotic diuresis?
- Author
-
de Berny, Quentin, Saint-Jacques, Camille, Santin, Aline, Mattioni, Sarah, Steichen, Olivier, Chieze, Rémi, Frochot, Vincent, Letavernier, Emmanuel, Lionnet, François, and Haymann, Jean-Philippe
- Subjects
- *
DIABETES insipidus , *SICKLE cell anemia , *DIURESIS , *VASOPRESSIN , *URINE - Abstract
The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule. NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus.
- Author
-
Strych, Lukáš, Černá, Monika, Hejnalová, Markéta, Zavoral, Tomáš, Komrsková, Pavla, Tejcová, Jitka, Bitar, Ibrahim, Sládková, Eva, Sýkora, Josef, and Šubrt, Ivan
- Subjects
- *
SINGLE nucleotide polymorphisms , *DIABETES insipidus , *GENETIC counseling , *GENETIC testing , *KIDNEY diseases , *MOLECULAR diagnosis - Abstract
Background: X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS). Methods: A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females. Results: By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands´ mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR. Conclusions: Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
20. Ifosfamide-induced nephrotoxicity in oncological patients.
- Author
-
Quiroz-Aldave, Juan Eduardo, Durand-Vásquez, María Del Carmen, Chávez-Vásquez, Freddy Shanner, Rodríguez-Angulo, Alexandra Noelia, Gonzáles-Saldaña, Sonia Elizabeth, Alcalde-Loyola, Carlos César, Coronado-Arroyo, Julia Cristina, Zavaleta-Gutiérrez, Francisca Elena, Concepción-Urteaga, Luis Alberto, Haro-Varas, Juan Carlos, and Concepción-Zavaleta, Marcio José
- Subjects
CANCER patients ,NEPHROTOXICOLOGY ,LITERATURE reviews ,DRUG side effects ,ALKYLATING agents - Abstract
Ifosfamide is an alkylating chemotherapeutic agent used in the treatment of various neoplasms. Its main adverse effects include renal damage. A comprehensive review was conducted, including 100 articles from the Scielo, Scopus, and EMBASE databases. Ifosfamide-induced nephrotoxicity is attributed to its toxic metabolites, such as acrolein and chloroacetaldehyde, which cause mitochondrial damage and oxidative stress in renal tubular cells. Literature review found a 29-year average age with no gender predominance and a mortality of 13%. Currently, no fully effective strategy exists for preventing ifosfamide-induced nephrotoxicity; however, hydration, forced diuresis, and other interventions are employed to limit renal damage. Long-term renal function monitoring is essential for patients treated with ifosfamide. Ifosfamide remains essential in neoplasm treatment, but nephrotoxicity, often compounded by coadministered drugs, poses diagnostic challenges. Preventive strategies are lacking, necessitating further research. Identifying timely risk factors can mitigate renal damage, and a multidisciplinary approach manages established nephrotoxicity. Emerging therapies may reduce ifosfamide induced nephrotoxicity. Ifosfamide is a type of chemotherapy used to treat different types of cancers. However, one of its main side effects is kidney damage. Researchers reviewed 100 articles from medical databases to understand how ifosfamide affects the kidneys. The kidney damage is caused by harmful substances produced when ifosfamide is broken down in the body. These substances can harm the cells in the kidneys. Studies have shown that 13% of the patients treated with ifosfamide can die. Currently, there is no perfect way to prevent kidney damage from ifosfamide, but doctors try to protect the kidneys by giving patients plenty of fluids and using other treatments, so it's important for patients who receive ifosfamide to have their kidney function checked regularly. Although ifosfamide is effective against cancer, its potential kidney side effects should be carefully considered by doctors when deciding on the best treatment for each patient. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
21. Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population
- Author
-
Saeed Ghasemi, Marzieh Mojbafan, Saeed Talebi, Nakysa Hooman, and Rozita Hoseini
- Subjects
antidiuretic hormone ,aquaporin‐2 ,arginine vasopressin receptor 2 ,nephrogenic diabetes insipidus ,Genetics ,QH426-470 - Abstract
Abstract Introduction Nephrogenic diabetes insipidus (NDI) is a rare genetic disease that causes water imbalance. The kidneys play a crucial role in regulating body fluids by controlling water balance through urine excretion. This highlights their essential function in managing the body's water levels, but individuals with NDI may have excess urine production (polyuria), that leads to excessive thirst (polydipsia). Untreated affected individuals may exhibit poor feeding and failure to thrive. This disease is caused by mutations in the AVPR2 and the AQP2 genes which have the X‐linked and autosomal recessive/dominant inheritance, respectively. Both of these genes are expressed in the kidney. Methods Twelve Iranian patients from 10 consanguineous families were studied in this project. DNA was extracted from the whole blood samples of the patients and their parents. All coding exons and exon‐intron boundaries of the AVPR2 and AQP2 genes were sequenced in the affected individuals, and the identified variants were investigated in the parents. All variants were analyzed according to the ACMG (American College of Medical Genetics and Genomics) guidelines. Results In this study, 6 different mutations were identified in the patients, including 5 in the AQP2 gene (c.439G>A, c.538G>A, c.140C>T, c.450T>A, and the novel c.668T>C) and 1 in the AVPR2 gene (c.337C>T) in the present study. Discussion As expected, all the detected mutations in this study were missense. According to the ACMG guideline, the identified mutations were categorized as pathogenic or likely pathogenic. Unlike previous studies which showed more than 90% of mutations were in the AVPR2 gene, and only less than 10% of the mutations were in the AQP2 gene, it was found that more than 90% of our identified mutations located in the AQP2 gene, and only one mutation was observed in the AVPR2 gene, which seems it may be a result of the high rate of consanguineous marriages in the Iranian population. We observed genotype‐phenotype correlation in some of our affected individuals, and some of the mutations were observed in unrelated families from same ethnicity which could be suggestive of a founder mutation.
- Published
- 2024
- Full Text
- View/download PDF
22. Autophagy and regulation of aquaporins in the kidneys
- Author
-
Xiangdong Guo, Yonglun Kong, Tae-Hwan Kwon, Chunling Li, and Weidong Wang
- Subjects
aquaporins ,autophagy ,nephrogenic diabetes insipidus ,urine concentration defect ,Internal medicine ,RC31-1245 ,Specialties of internal medicine ,RC581-951 - Abstract
Aquaporins (AQPs) are water channel proteins that facilitate the transport of water molecules across cell membranes. To date, seven AQPs have been found to be expressed in mammal kidneys. The cellular localization and regulation of the transport properties of AQPs in the kidney have been widely investigated. Autophagy is known as a highly conserved lysosomal pathway, which degrades cytoplasmic components. Through basal autophagy, kidney cells maintain their functions and structure. As a part of the adaptive responses of the kidney, autophagy may be altered in response to stress conditions. Recent studies revealed that autophagic degradation of AQP2 in the kidney collecting ducts leads to impaired urine concentration in animal models with polyuria. Therefore, the modulation of autophagy could be a therapeutic approach to treat water balance disorders. However, as autophagy is either protective or deleterious, it is crucial to establish an optimal condition and therapeutic window where autophagy induction or inhibition could yield beneficial effects. Further studies are needed to understand both the regulation of autophagy and the interaction between AQPs and autophagy in the kidneys in renal diseases, including nephrogenic diabetes insipidus.
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- 2023
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23. Treatment and long-term outcome in primary nephrogenic diabetes insipidus.
- Author
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Lopez-Garcia, Sergio C, Downie, Mallory L, Kim, Ji Soo, Boyer, Olivia, Walsh, Stephen B, Nijenhuis, Tom, Papizh, Svetlana, Yadav, Pallavi, Reynolds, Ben C, Decramer, Stéphane, Besouw, Martine, Carrascosa, Manel Perelló, Scola, Claudio La, Trepiccione, Francesco, Ariceta, Gema, Hummel, Aurélie, Dossier, Claire, Sayer, John A, Konrad, Martin, and Keijzer-Veen, Mandy G
- Subjects
- *
MENTAL illness , *DIABETES insipidus , *ATTENTION-deficit hyperactivity disorder , *CHRONIC kidney failure , *FULL-time employment , *BODY mass index - Abstract
Background Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. Methods Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. Results Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0–60) years and at last follow-up 14.0 (0.1–70) years. In adults, height was normal with a mean (standard deviation) score of −0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. Conclusion This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
24. Lithium poisoning and renal replacement therapy: pathophysiology and current clinical recommendations.
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Spatola, Leonardo, Maringhini, Silvio, Canale, Carmelinda, Granata, Antonio, and D'Amico, Maria
- Abstract
Lithium intoxication is still an undefined and underestimated disease, especially those cases requiring extracorporeal treatment. Lithium is a monovalent cation with small molecular mass of 7 Da that has been regularly and successfully used since 1950 in the treatment of mania and bipolar disorders. However, its careless assumption can lead to a wide spectrum of cardiovascular, central nervous system and kidney diseases in case of acute, acute on chronic and chronic intoxications. In fact, lithium serum range is strict between 0.6 and 1.3 mmol/L, with a mild lithium toxicity observed at the steady-state of 1.5–2.5 mEq/L, moderate toxicity when lithium reaches 2.5–3.5 mEq/L, and severe intoxication with observed serum levels > 3.5 mEq/L. Its favorable biochemical profile allows the complete filtration and partial reabsorption in the kidney due to the similarity to sodium and also the complete removal by renal replacement therapy, that should be considered in specific poisoning conditions. In this narrative and updated review we discussed a clinical case of lithium intoxication, the different pattern of diseases attributable to excessive lithium load and the current indications for extracorporeal treatment. [ABSTRACT FROM AUTHOR]
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- 2023
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25. Disorders of Water Balance: Hypernatremia
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Reddi, Alluru S. and Reddi, Alluru S.
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- 2023
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26. Aquaporins in Diabetes Insipidus
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Lu, H. A. Jenny, He, Jinzhao, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, and Yang, Baoxue, editor
- Published
- 2023
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27. Decline in Renal Concentration Ability in Lithium Treated Patients
- Published
- 2022
28. Diabète insipide néphrogénique induit par le lithium au cours d'une intoxication aiguë: à propos d'un cas.
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Echater, Sara, Mohammed, Hasnaoui, and Lechner, Evelyne
- Subjects
- *
DIABETES insipidus , *ACUTE kidney failure - Abstract
In case of dehydration, lithium can cause acute intoxication. This picture is mainly manifested by neurological disorders that can go as far as coma, digestive disorders, hydroelectrolytic disorders, and cardiovascular disorders. We report the case of a patient followed for bipolar disorder for 20 years and treated with lithium for 14 years and who presented an acute lithium intoxication resulting from a diabetes insipidus. Our objective is to underline the importance of good hydration and strict monitoring of lithium levels especially in situations favouring dehydration, notably the polyuria of diabetes insipidus. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Renal Toxicity of Psychotropic Medications
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How, Poh Choo, Xiong, Glen, Hategan, Ana, editor, Bourgeois, James A., editor, Gangji, Azim S., editor, and Woo, Tricia K.W., editor
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- 2022
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30. Desmopressin responding female nephrogenic diabetes insipidus: a case report
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Juyeon Lee, Hae Il Cheong, Jung Won Lee, and Ki Soo Pai
- Subjects
case reports ,fever of unknown origin ,nephrogenic diabetes insipidus ,polydipsia ,Internal medicine ,RC31-1245 ,Pediatrics ,RJ1-570 - Abstract
Nephrogenic diabetes insipidus, decreased ability to concentrate urine, with production of large amounts of urine, is caused by the refractory response of renal tubules to the action of antidiuretic hormone. This rare disorder, known as X-linked nephrogenic diabetes insipidus, is caused by a mutation in the AVPR2 gene. Because it is hereditary, most patients are male. This report highlights a case of nephrogenic diabetes insipidus in a 3-year 5-month-old female; upon presentation to the hospital, her symptoms included frequent urination and consumption of a significant amount of water, which had begun 2 years ago. The results of blood tests showed increased levels of serum antidiuretic hormone, and sellar magnetic resonance imaging showed no abnormality. The results of the water restriction test and the desmopressin administration test confirmed the diagnosis of nephrogenic diabetes insipidus showing a partial response to desmopressin. The results of genetic testing indicated the presence of an AVPR2 mutation, a heterozygous missense mutation (p.Val88Met), suggesting inheritance of X-linked nephrogenic diabetes insipidus. This report describes a significant case of symptomatic X-linked nephrogenic diabetes insipidus in a female patient who showed a partial response to desmopressin.
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- 2022
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31. β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus.
- Author
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Milano, Serena, Maqoud, Fatima, Rutigliano, Monica, Saponara, Ilenia, Carmosino, Monica, Gerbino, Andrea, Lucarelli, Giuseppe, Battaglia, Michele, Svelto, Maria, and Procino, Giuseppe
- Subjects
- *
ADRENERGIC agonists , *DIABETES insipidus , *LUTEINIZING hormone releasing hormone , *BLADDER , *EXCRETION , *KIDNEY tubules , *GENETIC disorders - Abstract
We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
32. Piège diagnostique : neurotoxicité au lithium avec lithémie normale.
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Tiv, Hugo, Vandelaer, Antoine, Delanaye, Pierre, Forte, Florence, and Bouquegneau, Antoine
- Abstract
Nous présentons ici le cas clinique d'une femme âgée de 54 ans, souffrant d'un trouble bipolaire, suivie en psychiatrie et traitée par lithium, un inhibiteur sélectif de la recapture de sérotonine (escitalopram) et lamotrigine, ayant présenté un tableau d'intoxication au lithium, avec une altération de l'état de conscience, à la suite d'une supposée erreur de gestion de son traitement. L'intoxication au lithium a été suggérée par la présence de symptômes neurologiques et la démonstration biologique d'un taux sérique dans des valeurs thérapeutiques normales à 1,2 mmol/L (N : 0,6–1,2 mmol/L). Les complications biologiques classiques en lien avec une intoxication au lithium (hypercalcémie, diabète insipide) ont conforté le diagnostic. La patiente a été prise en charge dans notre service de néphrologie et a bénéficié d'une épuration extra-rénale qui a conduit à une amélioration clinique et biologique, confortant ainsi le diagnostic d'intoxication au lithium malgré sa lithémie normale. Elle a ensuite été transférée en psychiatrie pour la suite de la prise en charge et l'adaptation du traitement psychotrope. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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33. Nephrogenic Diabetes Insipidus
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Sivasubramanian, Ramya, Meyers, Kevin E., and Alter, Craig A., editor
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- 2021
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34. Initial Evaluation of Polydipsia and Polyuria
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Marks, Brynn E., Stanley, Takara, editor, and Misra, Madhusmita, editor
- Published
- 2021
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35. Transient Antidiuretic Hormone Insufficiency Caused by Severe Hyperosmolar Hyperglycemic Syndrome Based on Nephrogenic Diabetes Insipidus
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Mizuki Gobaru, MD, Kentaro Sakai, MD, Yuki Sugiyama, MD, Chiaki Kohara, MD, Akiko Yoshimizu, MD, Rei Matsui, MD, Yuichi Sato, MD, Tatsuo Tsukamoto, MD, Kenji Ashida, MD, and Harumichi Higashi, MD
- Subjects
nephrogenic diabetes insipidus ,central diabetes insipidus ,hyperglycemic hyperosmolar syndrome ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background: The hyperosmolar hyperglycemic state (HHS), an acute complication of diabetes mellitus with plasma hyperosmolarity, promotes the secretion of anti-diuretic hormone (ADH) and reduces the storage of ADH. Magnetic resonance T1-weighted imaging reflects ADH storage in the posterior pituitary lobe, which disappears when the storage is depleted. Whether the HHS induces ADH depletion leading to clinical manifestations has been unclear. Case Report: A 55-year-old Japanese woman was admitted to our center because of mental disturbance and hypotension. She had received lithium carbonate for bipolar disorder and presented with polydipsia and polyuria from 15 years of age. On admission, she had mental disturbance (Glasgow Coma Scale, E4V1M1), hypotension (systolic blood pressure, 50 mmHg), and tachycardia (pulse rate, 123/min). Plasma glucose was 697 mg/dL osmolality was 476 mOsm/kg•H2O, and bicarbonate was 23.7 mmol/L. The diagnoses of HHS and hypovolemic shock were made. During treatment with fluid replacement and insulin therapy, the urine volume continued to be approximately 3 to 4 L/day, and an endocrine examination revealed ADH insufficiency and nephrogenic diabetes insipidus. Desmopressin 10 μg/day and trichlormethiazide 2 mg/day were necessary and administered, and the endogenous ADH secretion improved gradually. The signal intensity of the pituitary posterior lobe, initially decreased on magnetic resonance T1 images, was also improved. Conclusion: This patient had ADH insufficiency associated with ADH depletion due to hyperosmolarity and nephrogenic diabetes insipidus. Clinicians should be aware of the risk of the development of critical HHS and relative ADH insufficiency in patients being treated with lithium carbonate.
- Published
- 2021
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- View/download PDF
36. Dezmopresszinnel csökkenthető a polyuria a lítium által okozott nephrogen diabetes insipidusban. Rövid irodalmi áttekintés.
- Author
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János, RADÓ
- Subjects
DIABETES insipidus ,DESMOPRESSIN ,LITHIUM carbonate ,BIPOLAR disorder ,AMILORIDE - Abstract
Copyright of Hypertonia és Nephrologia is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2023
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37. Nephrogenic diabetes insipidus with new onset diabetic ketoacidosis in a child — challenges in fluid and electrolyte management.
- Author
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Tseng, Yu-Shan, Swaney, Nicole, Cashen, Katherine, Jain, Amrish, Ma, Nina, and Prout, Andrew
- Subjects
- *
FLUID therapy , *DIABETES insipidus , *WATER-electrolyte imbalances , *SHOCK (Pathology) , *PSYCHOSOCIAL factors , *OSMOLAR concentration , *HYPERTONIC saline solutions , *DIABETIC acidosis , *DISEASE complications - Abstract
Background: Intensive care management of diabetic ketoacidosis (DKA) is targeted to reverse ketoacidosis, replace the fluid deficit, and correct electrolyte imbalances. Adequate restoration of circulation and treatment of shock is key. Pediatric treatment guidelines of DKA have become standard but complexities arise in children with co-morbidities. Congenital nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by impaired kidney concentrating ability and treatment is challenging. NDI and DKA together have only been previously reported in one patient. Case diagnosis/treatment: We present the case of a 12-year-old male with NDI and new onset DKA with hyperosmolality. He presented in hypovolemic shock with altered mental status. Rehydration was challenging and isotonic fluid resuscitation resulted in increased urine output and worsening hyperosmolar state. Use of hypotonic fluid and insulin infusion led to lowering of serum osmolality faster than desired and increased the risk for cerebral edema. Despite the rapid decline in serum osmolality his mental status improved so we allowed him to drink free water mixed with potassium phosphorous every hour to match his urinary output (1:1 replacement) and continued 0.45% sodium chloride based on his fluid deficit and replacement rate with improvement in his clinical status. Conclusions: This case illustrates the challenges in managing hypovolemic shock, hyperosmolality, and extreme electrolyte derangements driven by NDI and DKA, as both disease processes drive excessive urine output, electrolyte and acid–base imbalances, and rapid fluctuation in osmolality. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
38. Molecular Characterization of an Aquaporin-2 Mutation Causing Nephrogenic Diabetes Insipidus.
- Author
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Qian Li, Bichao Lu, Jia Yang, Chao Li, Yanchun Li, Hui Chen, Naishi Li, Lian Duan, Feng Gu, Jianmin Zhang, and Weibo Xia
- Subjects
DIABETES insipidus ,AQUAPORINS ,ETIOLOGY of diabetes ,ENDOPLASMIC reticulum ,FUNCTIONAL analysis ,HYPERNATREMIA ,GENE transfection - Abstract
The aquaporin 2 (AQP2) plays a critical role in water reabsorption to maintain water homeostasis. AQP2 mutation leads to nephrogenic diabetes insipidus (NDI), characterized by polyuria, polydipsia, and hypernatremia. We previously reported that a novel AQP2 mutation (G215S) caused NDI in a boy. In this study, we aimed to elucidate the cell biological consequences of this mutation on AQP2 function and clarify the molecular pathogenic mechanism for NDI in this patient. First, we analyzed AQP2 expression in Madin-Darby canine kidney (MDCK) cells by AQP2-G215S or AQP2-WT plasmid transfection and found significantly decreased AQP2-G215S expression in cytoplasmic membrane compared with AQP2-WT, independent of forskolin treatment. Further, we found co-localization of endoplasmic reticulum (ER) marker (Calnexin) with AQP2-G215S rather than AQP2-WT in MDCK cells by immunocytochemistry. The functional analysis showed that MDCK cells transfected with AQP2-G215S displayed reduced water permeability compared with AQP2-WT. Visualization of AQP2 structure implied that AQP2-G215S mutation might interrupt the folding of the sixth transmembrane a-helix and/or the packing of α-helices, resulting in the misfolding of monomer and further impaired formation of tetramer. Taken together, these findings suggested that AQP2-G215S was misfolded and retained in the ER and could not be translocated to the apical membrane to function as a water channel, which revealed the molecular pathogenic mechanism of AQP2-G215S mutation and explained for the phenotype of NDI in this patient. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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39. A novel AVPR2 gene mutation in a Chinese pedigree with nephrogenic diabetes insipidus.
- Author
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Zhao Y, Li K, Chen C, Lv X, Wang Y, Ma L, Fu S, and Liu J
- Abstract
Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 ( AVPR2 ) gene or the aquaporin 2 ( AQP2 ) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2 , and leads to reduced tubular reabsorption of water.
- Published
- 2024
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40. Renal Aquaporins in Health and Disease
- Author
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Kortenoeven, Marleen L. A., Olesen, Emma T. B., Fenton, Robert A., Hamilton, Kirk L., editor, and Devor, Daniel C., editor
- Published
- 2020
- Full Text
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41. A case of nephrogenic diabetes insipidus likely caused by anti-neutrophil cytoplastic antibody-associated vasculitis
- Author
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Asakura, Kei, Ogata, Hiroaki, Omatsu, Mutsuko, Yamamoto, Masahiro, Yoshida, Kiryu, and Ito, Hidetoshi
- Published
- 2023
- Full Text
- View/download PDF
42. Nephrogenic diabetes insipidus: a comprehensive overview.
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Vaz de Castro, Pedro Alves Soares, Bitencourt, Letícia, de Oliveira Campos, Juliana Lacerda, Fischer, Bruna Luisa, Soares de Brito, Stephanie Bruna Camilo, Soares, Beatriz Santana, Drummond, Juliana Beaudette, and Simões e Silva, Ana Cristina
- Abstract
Nephrogenic diabetes insipidus (NDI) is characterized by the inability to concentrate urine that results in polyuria and polydipsia, despite having normal or elevated plasma concentrations of arginine vasopressin (AVP). In this study, we review the clinical aspects and diagnosis of NDI, the various etiologies, current treatment options and potential future developments. NDI has different clinical manifestations and approaches according to the etiology. Hereditary forms of NDI are mainly caused by mutations in the genes that encode key proteins in the AVP signaling pathway, while acquired causes are normally associated with specific drug exposure, especially lithium, and hydroelectrolytic disorders. Clinical manifestations of the disease vary according to the degree of dehydration and hyperosmolality, being worse when renal water losses cannot be properly compensated by fluid intake. Regarding the diagnosis of NDI, it is important to consider the symptoms of the patient and the diagnostic tests, including the water deprivation test and the baseline plasma copeptin measurement, a stable surrogate biomarker of AVP release. Without proper treatment, patients may developcomplications leading to high morbidity and mortality, such as severe dehydration and hypernatremia. In that sense, the treatment of NDI consists in decreasing the urine output, while allowing appropriate fluid balance, normonatremia, and ensuring an acceptable quality of life. Therefore, therapeutic options include nonpharmacological interventions, including sufficient water intake and a low-sodium diet, and pharmacological treatment. The main medications used for NDI are thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride, used isolated or in combination. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
43. Congenital nephrogenic diabetes insipidus accompanied with central nephrogenic diabetes secondary to pituitary surgery -a case report
- Author
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Wei Zhang, Yimin Shen, Yuezhong Ren, Yvbo Xin, and Lijun Wang
- Subjects
Polyuria ,Nephrogenic diabetes insipidus ,Central nephrogenic diabetes ,AVPR2 mutation ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Abstract Background Diabetes insipidus (DI) can be a common cause of polydipsia and polyuria. Here, we present a case of congenital nephrogenic diabetes insipidus (CNDI) accompanied with central diabetes insipidus (CDI) secondary to pituitary surgery. Case presentation A 24-year-old Chinese woman came to our hospital with the complaints of polydipsia and polyuria for 6 months. Six months ago, she was detected with pituitary apoplexy, and thereby getting pituitary surgery. However, the water deprivation test demonstrated no significant changes in urine volume and urine gravity in response to fluid depression or AVP administration. In addition, the genetic results confirmed a heterozygous mutation in arginine vasopressin receptor type 2 (AVPR2) genes. Conclusions She was considered with CNDI as well as acquired CDI secondary to pituitary surgery. She was given with hydrochlorothiazide (HCTZ) 25 mg twice a day as well as desmopressin (DDAVP, Minirin) 0.1 mg three times a day. There is no recurrence of polyuria or polydipsia observed for more than 6 months. It can be hard to consider AVPR2 mutation in female carriers, especially in those with subtle clinical presentation. Hence, direct detection of DNA sequencing with AVPR2 is a convenient and accurate method in CNDI diagnosis.
- Published
- 2021
- Full Text
- View/download PDF
44. Impact of the 2016 Kumamoto earthquake on patients with nephrogenic diabetes insipidus and preparations for the future
- Author
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Hiroshi Tamura, Hiroko Nagata, Keishiro Furuie, Shohei Kuraoka, Yuko Hidaka, and Hitoshi Nakazato
- Subjects
children ,disasters ,Nephrogenic diabetes insipidus ,water supply ,Medicine ,Medicine (General) ,R5-920 - Abstract
Abstract Patients with nephrogenic diabetes insipidus should establish a support network system by contacting the government to ensure that water can be preferentially obtained in the event of a disaster and create and carry a medical alert card.
- Published
- 2021
- Full Text
- View/download PDF
45. Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
- Author
-
University of Aarhus
- Published
- 2018
46. β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus
- Author
-
Serena Milano, Fatima Maqoud, Monica Rutigliano, Ilenia Saponara, Monica Carmosino, Andrea Gerbino, Giuseppe Lucarelli, Michele Battaglia, Maria Svelto, and Giuseppe Procino
- Subjects
AQP2 ,NKCC2 ,mirabegron ,beta3-adrenoreceptor ,nephrogenic diabetes insipidus ,diuresis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.
- Published
- 2023
- Full Text
- View/download PDF
47. X-Linked Kidney Disorders in Women.
- Author
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Quinlan, Catherine and Rheault, Michelle N.
- Subjects
DIABETES insipidus ,X chromosome ,ANGIOKERATOMA corporis diffusum ,KIDNEYS ,GENETIC disorders ,RICKETS ,GENETIC mutation ,NEPHRITIS ,PHENOTYPES - Abstract
A number of genes that cause inherited kidney disorders reside on the X chromosome. Given that males have only a single active X chromosome, these disorders clinically manifest primarily in men and boys. However, phenotypes in female carriers of X-linked kidney conditions are becoming more and more recognized. This article reviews the biology of X inactivation as well as the kidney phenotype in women and girls with a number of X-linked kidney disorders including Alport syndrome, Fabry disease, nephrogenic diabetes insipidus, X-linked hypophosphatemic rickets, Dent disease, and Lowe syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
48. Bendamustine-induced nephrogenic diabetes insipidus – A case report.
- Author
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Desjardins, Audrey, Le-Nguyen, Viviane, Turgeon-Mallette, Léa, Vo, Chloé, Boudreault, Jean-Samuel, Rioux, Jean-Philippe, Feng, Xue, and Veilleux, Amélie
- Subjects
- *
DIABETES insipidus , *DESMOPRESSIN , *NITROGEN mustards , *PARENTERAL infusions , *TREATMENT effectiveness , *ALKYLATING agents , *INTRANASAL medication - Abstract
Introduction: In patients with relapsed or refractory lymphoma, high-dose chemoimmunotherapy with subsequent autologous hematopoietic cell transplantation (HCT) is a standard of care. Bendamustine, an alkylating agent, is used in the BeEAM (bendamustine, etoposide, cytarabine, melphalan) protocol for conditioning therapy before autologous HCT in patients with relapsed or refractory lymphoma who are eligible for transplant. There is no consensus regarding an optimal salvage regimen and the approach varies according to toxicity. Case report: We present a case of partial nephrogenic diabetes insipidus after receiving bendamustine, as part of the BeEAM protocol. Management and outcome: The patient was managed with parenteral fluid administration and intranasal desmopressin before the condition resolved on its own. Discussion: We summarize published reports of bendamustine-induced diabetes insipidus. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
49. LITHIUM AND ENDOCRINE DYSFUNCTION.
- Author
-
LERENA, VANINA S., LEÓN, NATALIA S., SOSA, SOLEDAD, DELIGIANNIS, NATALIA G., DANILOWICZ, KARINA, and RIZZO, LEONARDO F. L.
- Abstract
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- Published
- 2022
50. Nephrogenic Diabetes Insipidus
- Author
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Balla, András, Hunyady, László, Igaz, Peter, editor, and Patócs, Attila, editor
- Published
- 2019
- Full Text
- View/download PDF
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