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nephrogenic diabetes insipidus

Nsabimana A Uwumugambi, Vaishali Sanchorawala, Anthony C Shelton, Lauren Stern, Craig E Gordon
Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis...
October 22, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Michael A Bohl, James Forseth, Peter Nakaji
BACKGROUND: Arginine vasopressin (AVP) is a common second-line or third-line vasopressor used in critically ill neurosurgical patients. Neurosurgical indications include hyperdynamic therapy for vasospasm, maintenance of cerebral perfusion pressure in patients with intracranial hypertension, and prevention of hypotension in patients with sepsis. CASE DESCRIPTION: A series of six neurosurgical patients receiving AVP infusions developed severe but transient diabetes insipidus (tDI) after cessation of AVP...
October 11, 2016: World Neurosurgery
Benjamin Derman, Milli Jain, Elizabeth McAninch, Casey Gashti
A 59-year-old man presented with polyuria and polydipsia immediately following his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. He initially compensated by increasing his oral fluid intake at home, but later developed septic shock and was admitted with orders to be kept nil per os (NPO). This prompted an episode of acute hypernatremia during which he exhibited continued polyuria with inappropriately dilute urine. Desmopressin challenge yielded no response in the urine osmolality, indicating a nephrogenic source of his diabetes insipidus (DI)...
October 10, 2016: Clinical Nephrology
Pui W Cheung, Naohiro Nomura, Anil V Nair, Nutthapoom Pathomthongtaweechai, Lars Ueberdiek, Hua A Jenny Lu, Dennis Brown, Richard Bouley
Nephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been sought. Successful identification of compounds by our high-throughput chemical screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors stimulate AQP2 trafficking and reduce urine output...
October 2016: Journal of the American Society of Nephrology: JASN
Priyakshi Kalita-DE Croft, Jennifer J Bedford, John P Leader, Robert J Walker
AIM: Long-term administration of lithium has been associated with the development of a chronic interstitial fibrosis in addition to nephrogenic diabetes insipidus (NDI). Earlier studies have demonstrated that amiloride, by blocking the epithelial sodium channel ENaC and thus preventing lithium uptake into the principal cells of the collecting ducts, can partially reverse lithium-induced NDI. However, there are no long-term studies examining whether or not amiloride also modifies the progressive chronic interstitial fibrosis and tubular atrophy often evident with long term lithium exposure...
September 28, 2016: Nephrology
Hans K H Ng, Kaleeckal G Harikumar, Laurence J Miller, Billy K C Chow
The involvement of secretin (SCT) and secretin receptor (SCTR) in regulating body water homeostasis is well established. Identified as one of the vasopressin (Vp)-independent mechanisms in fluid balance, SCT regulates aquaporin 2 (AQP2) in the kidney distal collecting duct cells through activating intracellular cAMP production. This ability to bypass Vp-mediated water reabsorption in kidney implicates SCT's potential to treat nephrogenic diabetes insipidus (NDI). Research on NDI in the past has largely been focused on the searching for mutations in vasopressin receptor 2 (AVPR2), while the functional relationship between SCTR, AVPR2 and NDI remains unclear...
2016: PloS One
Abdulah El Tarazi, Yoann Lussier, Sandra Da Cal, Pierre Bissonnette, Daniel G Bichet
Aquaporin-2 (AQP2) is a homotetrameric water channel responsible for the final water reuptake in the kidney. Mutations in the protein induce nephrogenic diabetes insipidus (NDI), which challenges the water balance by producing large urinary volumes. Although recessive AQP2 mutations are believed to generate non-functional and monomeric proteins, the literature identifies several mild mutations which suggest the existence of mixed wt/mut tetramers likely to carry function in heterozygotes. Using Xenopus oocytes, we tested this hypothesis and found that mild mutants (V24A, D150E) can associate with wt-AQP2 in mixed heteromers, providing clear functional gain in the process (62 ± 17% and 63 ± 17% increases, respectively), conversely to the strong monomeric R187C mutant which fails to associate with wt-AQP2...
2016: Scientific Reports
Graça Soveral, Angela Casini
INTRODUCTION: Since the discovery of aquaporin-1 (AQP1) as a water channel, more than 2,000 articles, reviews and chapters have been published. The wide tissue expression, functional and biological roles have documented the major and essential physiological importance of these channels both in health and disease. Thus, over the years, studies have revealed essential importance of aquaporins in mammalian pathophysiology revealing aquaporins as potential drug targets. AREAS COVERED: Starting from a brief description of the main structural and functional features of aquaporins, their roles in physiology and pathophysiology of different human diseases, this review describes the main classes of small molecules and biologicals patented, published from 2010 to 2015, able to regulate AQPs for diagnostic and therapeutic applications...
September 13, 2016: Expert Opinion on Therapeutic Patents
Noriko Makita, Tomohiko Sato, Yuki Yajima-Shoji, Junichiro Sato, Katsunori Manaka, Makiko Eda-Hashimoto, Masanori Ootaki, Naoki Matsumoto, Masaomi Nangaku, Taroh Iiri
Disease-causing mutations in GPCR genes, including V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to the defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously. Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak...
September 6, 2016: Journal of Biological Chemistry
Zhijuan Dai, Luya Ruan, Jian Jin, Yanying Qian, Liang Wang, Zhen Shi, Chaoming Wu
OBJECTIVE: To detect potential mutation in a pedigree affected with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and directly sequenced. RESULTS: The patient presented polyuria and polydipsia postnatally...
October 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Wei-Hong Guo, Qiang Li, Hong-Yan Wei, Hong-Yan Lu, Hui-Qi Qu, Mei Zhu
Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 (AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test...
August 25, 2016: Journal of International Medical Research
Jeff M Sands, Janet D Klein
Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for Nephrogenic Diabetes Insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water channel, or in another key inner medullary transport protein, the UT-A1 urea transporter...
August 17, 2016: American Journal of Physiology. Renal Physiology
Jonathan Baird-Gunning, Tom Lea-Henry, Lotte C G Hoegberg, Sophie Gosselin, Darren M Roberts
Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination...
August 11, 2016: Journal of Intensive Care Medicine
Orhan Efe, Janet D Klein, Lauren M LaRocque, Huiwen Ren, Jeff M Sands
Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/ kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily...
July 21, 2016: JCI Insight
Marie Muyldermans, Serge Jennes, Stuart Morrison, Olivier Soete, Pierre-Michel François, Elkana Keersebilck, Thomas Rose, Olivier Pantet
OBJECTIVE: To describe a case of partial nephrogenic diabetes insipidus in a burned patient after prolonged delivery of low inspired concentrations of sevoflurane via an Anesthetic Conserving Device. DATA SOURCES: Clinical observation. STUDY SELECTION: Case report. DATA EXTRACTION: Relevant clinical information. DATA SYNTHESIS: A 34-year-old man was admitted with burns covering 52% of his total body surface area...
July 13, 2016: Critical Care Medicine
Jo Ann Janovick, Timothy P Spicer, Emery Smith, Thomas D Bannister, Terry Kenakin, Louis Scampavia, P Michael Conn
Pharmacoperones rescue misrouted mutants of the vasopressin receptor type 2 (V2R) and enable them to traffic to the correct biological locus where they function. Previously, a library of nearly 645,000 structures was interrogated with a high throughput screen; pharmacoperones were identified for V2R mutants with a view toward correcting the underlying mutational defects in nephrogenic diabetes insipidus. In the present study, an orthologous assay was used to evaluate hits from the earlier study. We found no consistent relation between antagonism or agonism and pharmacoperone activity...
October 15, 2016: Molecular and Cellular Endocrinology
Peili Zheng, Yu Lin, Feifei Wang, Renfei Luo, Tiezheng Zhang, Shan Hu, Pinning Feng, Xinling Liang, Chunling Li, Weidong Wang
Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenybutyric acid (4-PBA) improves urinary concentrating defect in a lithium-treated rats. Wistar rats have received lithium (40 mmol/kg food), 4-PBA (320 mg/kg BW by gavage every day), or no treatment (control) for two weeks and some of them were dehydrated for 24 hours...
July 6, 2016: American Journal of Physiology. Renal Physiology
Soham Rej, Shamira Pira, Victoria Marshe, André Do, Dominique Elie, Karl J Looper, Nathan Herrmann, Daniel J Müller
PURPOSE: Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease. METHODS: We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium's effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers...
June 29, 2016: International Urology and Nephrology
Anatoly Tiulpakov, Carl W White, Rekhati S Abhayawardana, Heng B See, Audrey S Chan, Ruth M Seeber, Julian I Heng, Ivan Dedov, Nathan J Pavlos, Kevin D G Pfleger
Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a genetic disease first described in 2 unrelated male infants with severe symptomatic hyponatremia. Despite undetectable arginine vasopressin levels, patients have inappropriately concentrated urine resulting in hyponatremia, hypoosmolality, and natriuresis. Here, we describe and functionally characterize a novel vasopressin type 2 receptor (V2R) gain-of-function mutation. An L312S substitution in the seventh transmembrane domain was identified in a boy presenting with water-induced hyponatremic seizures at the age of 5...
August 2016: Molecular Endocrinology
Werner Keenswijk, Johan Vande Walle
A 4-year-old boy was referred to the nephrologist with daytime urinary incontinence and suspicion of an overactive bladder. At the age of 17 months he had been referred to the pediatric endocrinologist because of polyuria and polydipsia in order to exclude diabetes insipidus. Repeated water deprivation tests and a magnetic resonance imaging scan of the brain were normal. Diabetes insipidus was excluded, and primary polydipsia was thought to be most likely since diabetes mellitus also had been excluded. At the current presentation, he drank up to 3 L a day and quite often had wet diapers...
June 27, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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