Nephrogenic+Diabetes+Insipidus

=**Nephrogenic Diabetes Insipidus**=



Root cause of disease: X-linked recessive Vasopressin V2 receptor gene in 90% of cases. Can also be caused by autosomal recessive or autosomal dominant Aquaporin-2 gene.


 * __Affected cell types/tissues/organs/systems:__** This disease involves a defect in the distal convoluted tubules of the nephrons of the kidneys. This causes a disruption in the normal reabsorption of water back into the bloodstream.


 * __Historical background:__** Although no famous individuals have admitted to having this disease, it does have an interesting historical background. This disease has been known for hundreds of years, yet it wasn’t clearly defined from Diabetes Mellitus until the 17th century due to the symptoms presenting very similarly. Until 1912 this disease was thought to have been a renal complication until the removal of a lobe of the pituitary brought on the complications of the disease. Around 1950 it was found that the posterior pituitary is what actually contains the Anti-diuretic hormone, and these hormones are actually created in the hypothalamus and just stored in the posterior pituitary.


 * __Common symptoms:__** Common symptoms include polydipsia (Excessive thirst) and polyuria (excessive urination). If left untreated complications lead to extreme dehydration, electrolyte imbalance, and even death.


 * __Standard treatments:__** Treatment of nephrogenic DI is usually an increase in fluid intake to reach fluid output and drugs to lower urine output like anti-inflammatory medication and diuretics. Diuretics may seem contrary to what is believed to help but their ultimate increase in Na and water reabsorption in the Proximal Convoluted Tubule overall decreases urine output. A low solute diet (low sodium and low protein content) is recommended to reduce renal osmolarity. However, these dietary restrictions can pose nutritional risks and are offered under caution.


 * __Current research:__** Current research on nephrogenic DI focuses on the cause and treatment of the disease. The results of the study by Postina et al 2000 demonstrate that different mutations located close to each other in the second extracellular loop of the vasopressin gene have different consequences on the function and expression of the V2 receptor. This mutation hinders both correct folding and transport of the receptor to the plasma membrane and lowers the affinity for its ligands, or AVP. The reduced affinity of AVP causes the symptoms of nephrogenic DI. A study done by Grofeanu et al in 2005 found that drugs can cause this disease, and went to determine the reversibility of such occurrences. 24 of the 30 causes were shown to induce reversible forms of NDI. The time necessary for recovery is related to the duration of exposure as found by the study. This is important because it indicates that NDI can be reversed in certain cases, and thus lead to a full recovery.

Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2008). //Molecular Biology of the Cell// (5th ed., p. 583). New York, NY: Garland Science. Garofeanu, C., Weir, M., Rosas-Arellano, M., Henson, G., Garg, A., & Clark, W. (2005, April). Causes of reversible nephrogenic diabetes insipidus: A systematic review. //American Journal of Kidney Diseases//, //45//(4), 626-637. doi:10.1053/j.ajkd.2005.01.008 Postina, R., Ufer, E., Pfeiffer, R., Knoers, N., & Fahrenholza, F. (2000, June). Misfolded vasopressin V2 receptors caused by extracellular point mutations entail congential nephrogenic diabetes insipidus. //Molecular and Cellular Endocrinology//, //164//(2), 31-39. Sindhwani, A., Singhal, D., & Jerath, N. (2007, June). Nephrogenic Diabetes Insipidus. //Apollo Medicine//, //4//(2), 149-151. doi:10.1016/S0976-0016(11)60125-7
 * __References:__**