Chapter 524 Nephrogenic Diabetes Insipidus Rajasree Sreedharan, Ellis D. Avner Nephrogenic diabetes insipidus (NDI) is a rare congenital or, more commonly, acquired, disorder of water metabolism characterized by an inability to concentrate urine, even in the presence of antidiuretic hormone (ADH). The most common pattern of inheritance in congenital NDI is as an X-linked recessive disorder. Rarely, affected females are seen, presumably secondary to unfavorable X-chromosome inactivation. About 10% of cases of congenital NDI are inherited as autosomal dominant or recessive disorders, with males and females affected equally. The clinical phenotype of autosomal recessive forms is similar to that of the X-linked form. Secondary (acquired), either partial or complete, forms of NDI are not uncommon and may be seen in any disorder affecting renal tubular function including obstructive uropathies, acute or chronic renal failure, renal cystic diseases, interstitial nephritis, nephrocalcinosis, or toxic nephropathy due to hypokalemia, hypercalcemia, lithium, or amphotericin B. Pathogenesis The ability to concentrate urine (and thus absorb water) requires the presence of an intact concentrating gradient in the renal medulla and the ability to modulate water permeability in the collecting tubule. The latter is mediated by ADH (also called arginine vasopressin [AVP]), which is synthesized in the hypothalamus and stored in the posterior pituitary. Under basal situations, the collecting tubule is impermeable to water. However, in response to increased serum osmolarity (as detected by osmoreceptors in the hypothalamus) and/or severe volume depletion, ADH is released into the systemic circulation. It then binds to its receptor, vasopressin V2 (AVPR2), on the basolateral membrane of the collecting tubule cell. Binding of the hormone to its receptor activates a cyclic adenosine monophosphate(cAMP)-dependent cascade that results in movement of preformed water channels (aquaporin 2 [AQP2]) to the luminal membrane of the collecting duct, rendering it permeable to water. Defects in the AVPR2 gene cause the more common X-linked form of NDI. Mutations in the AQP2 Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Rumination, Pica, and Elimination (Enuresis, Encopresis) Disorders Adolescent Pregnancy Neisseria gonorrhoeae (Gonococcus) Blastomycosis (Blastomyces dermatitidis) Stay updated, free articles. Join our Telegram channel Join Tags: Nelson Textbook of Pediatrics Expert Consult Jun 18, 2016 | Posted by admin in PEDIATRICS | Comments Off on Nephrogenic Diabetes Insipidus Full access? Get Clinical Tree
Chapter 524 Nephrogenic Diabetes Insipidus Rajasree Sreedharan, Ellis D. Avner Nephrogenic diabetes insipidus (NDI) is a rare congenital or, more commonly, acquired, disorder of water metabolism characterized by an inability to concentrate urine, even in the presence of antidiuretic hormone (ADH). The most common pattern of inheritance in congenital NDI is as an X-linked recessive disorder. Rarely, affected females are seen, presumably secondary to unfavorable X-chromosome inactivation. About 10% of cases of congenital NDI are inherited as autosomal dominant or recessive disorders, with males and females affected equally. The clinical phenotype of autosomal recessive forms is similar to that of the X-linked form. Secondary (acquired), either partial or complete, forms of NDI are not uncommon and may be seen in any disorder affecting renal tubular function including obstructive uropathies, acute or chronic renal failure, renal cystic diseases, interstitial nephritis, nephrocalcinosis, or toxic nephropathy due to hypokalemia, hypercalcemia, lithium, or amphotericin B. Pathogenesis The ability to concentrate urine (and thus absorb water) requires the presence of an intact concentrating gradient in the renal medulla and the ability to modulate water permeability in the collecting tubule. The latter is mediated by ADH (also called arginine vasopressin [AVP]), which is synthesized in the hypothalamus and stored in the posterior pituitary. Under basal situations, the collecting tubule is impermeable to water. However, in response to increased serum osmolarity (as detected by osmoreceptors in the hypothalamus) and/or severe volume depletion, ADH is released into the systemic circulation. It then binds to its receptor, vasopressin V2 (AVPR2), on the basolateral membrane of the collecting tubule cell. Binding of the hormone to its receptor activates a cyclic adenosine monophosphate(cAMP)-dependent cascade that results in movement of preformed water channels (aquaporin 2 [AQP2]) to the luminal membrane of the collecting duct, rendering it permeable to water. Defects in the AVPR2 gene cause the more common X-linked form of NDI. Mutations in the AQP2 Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Rumination, Pica, and Elimination (Enuresis, Encopresis) Disorders Adolescent Pregnancy Neisseria gonorrhoeae (Gonococcus) Blastomycosis (Blastomyces dermatitidis) Stay updated, free articles. Join our Telegram channel Join Tags: Nelson Textbook of Pediatrics Expert Consult Jun 18, 2016 | Posted by admin in PEDIATRICS | Comments Off on Nephrogenic Diabetes Insipidus Full access? Get Clinical Tree
