Nephrogenic+Diabetes+Insipidus

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 * The video above shows how ADH is an essential role in urination and the effects on the person when the ADH is not released.
 * Insipidus means without taste or perceptible flavor, and diabetes means excessive discharge of urine; dia means through and bainein means to go
 * Caused by a non-functional aquaporin protein
 * Causes the excretion of large volumes of dilute urine
 * Improper response to antidiuretic hormone ADH
 * ADH function: balance between fluid intake and urine excretion
 * Also directs the kidneys to concentrate urine by reabsorbing some of the water into the bloodstream
 * This decreases the ability of the kidney to concentrate the urine by removing free water
 * Urine content does not have elevated glucose concentration
 * Caused by mutations in at least two genes
 * About 90% of patients with the hereditary form of the disease have mutations in AVPR2 gene
 * Name: arginine vasopressin receptor 2
 * Provides instructions for making a protein called vasopressin V2 receptor
 * Works with hormone vasopressin or ADH in the kidneys
 * The vasopressin receptor is found in collecting ducts
 * The function is for ADH and vasopressin V2 receptor to interact to trigger chemical reactions that control water balance
 * ADH binds to vasopressin V2 receptor and directs kidneys to concentrate urine by reabsorbing water into blood
 * There is an incorrect fold in the vasopressin V2 receptor protein which causes the incorrect 3-dimensional shape
 * The cell is unable to reach the cell surface so it can interact with ADH
 * Another mutation in the AVPR2 gene prevents the production of any vasopressin V2 receptor protein or lead to a version of the protein that reaches the cell surface but cannot bind with ADH
 * Without a functional vasopressin receptor, the kidneys do not respond to ADH
 * Collecting ducts no longer reabsorb the water, resulting excess urine
 * The AVPR2 gene is located on the X chromosome

Figure 1: AVPR2 mutations, indicated by the red circles, cause the vasopressin protein to fold incorrectly. These mutations do not allow the protein to communicate with ADH, which does not trigger reabsorption of water and increases urination.


 * 10% have mutations in aquaporin 2 AQP2 gene
 * AQP2 function: provides instructions for making a protein called aquaporin 2
 * Protein forms a channel that carries water molecules across cell membranes found in the kidneys in the collecting duct
 * Collecting duct- series of small tubes that reabsorb water from kidneys into bloodstream
 * The placement of aquaporin 2 channel is controlled by ADH
 * When fluid intake is low, more ADH and vise versa
 * The hormone triggers chemical reactions that insert AQP2 water channels in the membrane of collecting duct cells, which allow water to reabsorb back into the blood
 * Mutations in AQP2 protein fold in an incorrect 3-D shape
 * The protein is not stuck in the cell and cannot reach the cell membrane, thus it cannot transport water molecules
 * If AQP2 water channels cannot be inserted in the membrane, there is no response to ADH
 * The AQP2 gene is located on chromosome 12


 * These genes provide instructions for making proteins that help determine how much water is excreted in urine
 * Mutations in AVPR2 or AQP2 prevent the kidneys from responding to ADH
 * The kidneys do not reabsorb water and the body makes too much urine
 * This is an X-linked recessive pattern
 * AVPR2 is located on the x chromosome which is one of the two sex chromosomes
 * When NDI is caused by AQP2 gene, it can be autosomal recessive or autosomal dominant pattern of inheritance (less common)

References code Daniel G. Bichet, Nephrogenic [|diabetes] insipidus, The American Journal of Medicine, Volume 105, Issue 5, November 1998, Pages 431-442, ISSN 0002-9343, 10.1016/S0002-9343(98)00301-5. (http://www.sciencedirect.com/science/article/pii/S0002934398003015) code