Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Pediatric Nephrology
Erschienen in: Pediatric Nephrology 12/2012

01.12.2012 | Review

Congenital nephrogenic diabetes insipidus: the current state of affairs

verfasst von: Daniel Wesche, Peter M. T. Deen, Nine V. A. M. Knoers

Erschienen in: Pediatric Nephrology | Ausgabe 12/2012

Einloggen, um Zugang zu erhalten

Abstract

The anti-diuretic hormone arginine vasopressin (AVP) is released from the pituitary upon hypovolemia or hypernatremia, and regulates water reabsorption in the renal collecting duct principal cells. Binding of AVP to the arginine vasopressin receptor type 2 (AVPR2) in the basolateral membrane leads to translocation of aquaporin 2 (AQP2) water channels to the apical membrane of the collecting duct principal cells, inducing water permeability of the membrane. This results in water reabsorption from the pro-urine into the medullary interstitium following an osmotic gradient. Congenital nephrogenic diabetes insipidus (NDI) is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their pro-urine, which leads to a high risk of dehydration. This review focuses on the current knowledge regarding the cell biological aspects of congenital X-linked, autosomal-recessive and autosomal-dominant NDI while specifically addressing the latest developments in the field. Based on deepened mechanistic understanding, new therapeutic strategies are currently being explored, which we also discuss here.
Literatur
1.
van Lieburg AF, Knoers NV, Monnens LA (1999) Clinical presentation and follow-up of 30 patients with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 10:1958–1964PubMed
2.
Forssman H (1955) Is hereditary diabetes insipidus of nephrogenic type associated with mental deficiency? Acta Psychiatr Neurol Scand 30:577–587PubMedCrossRef
3.
Macaulay D, Watson M (1967) Hypernatraemia in infants as a cause of brain damage. Arch Dis Child 42:485–491PubMedCrossRef
4.
Kanzaki S, Omura T, Miyake M, Enomoto S, Miyata I, Ishimitsu H (1985) Intracranial calcification in nephrogenic diabetes insipidus. JAMA 254:3349–3350PubMedCrossRef
5.
Schofer O, Beetz R, Kruse K, Rascher C, Schutz C, Bohl J (1990) Nephrogenic diabetes insipidus and intracerebral calcification. Arch Dis Child 65:885–887PubMedCrossRef
6.
Hoekstra JA, van Lieburg AF, Monnens LA, Hulstijn-Dirkmaat GM, Knoers VV (1996) Cognitive and psychosocial functioning of patients with congenital nephrogenic diabetes insipidus. Am J Med Genet 61:81–88PubMedCrossRef
7.
Shalev H, Romanovsky I, Knoers NV, Lupa S, Landau D (2004) Bladder function impairment in aquaporin-2 defective nephrogenic diabetes insipidus. Nephrol Dial Transplant 19:608–613PubMedCrossRef
8.
Makaryus AN, McFarlane SI (2006) Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med 73:65–71PubMedCrossRef
9.
Marples D, Christensen S, Christensen EI, Ottosen PD, Nielsen S (1995) Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest 95:1838–1845PubMedCrossRef
10.
Klein JD, Gunn RB, Roberts BR, Sands JM (2002) Down-regulation of urea transporters in the renal inner medulla of lithium-fed rats. Kidney Int 61:995–1002PubMedCrossRef
11.
Timmer RT, Sands JM (1999) Lithium intoxication. J Am Soc Nephrol 10:666–674PubMed
12.
Trepiccione F, Christensen BM (2010) Lithium-induced nephrogenic diabetes insipidus: new clinical and experimental findings. J Nephrol 23(Suppl 16):S43–S48PubMed
13.
Amlal H, Krane CM, Chen Q, Soleimani M (2000) Early polyuria and urinary concentrating defect in potassium deprivation. Am J Physiol Renal Physiol 279:F655–F663PubMed
14.
Elkjaer M-L, Kwon T-H, Wang W, Nielsen J, Knepper MA, Frøkiaer J, Nielsen S (2002) Altered expression of NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats. Am J Physiol Renal Physiol 283:F1376–F1388PubMed
15.
Wang W, Li C, Kwon T-H, Miller RT, Knepper M, Frøkiaer J, Nielsen S (2004) Reduced expression of renal Na+ transporters in rates with PTH-induced hypercalcemia. Am J Physiol Renal Physiol 286:F535–F545
16.
Earm JH, Christensen BM, Frokiaer J, Marples D, Han JS, Knepper MA, Nielsen S (1998) Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats. J Am Soc Nephrol 9:2181–2193PubMed
17.
Sands JM, Naruse M, Jacobs JD, Wilcox JN, Klein JD (1996) Changes in aquaporin-2 protein contribute to the urine concentrating defect in rats fed a low-protein diet. J Clin Invest 97:2807–2814PubMedCrossRef
18.
Frokiaer J, Li C, Shi Y, Jensen A, Praetorius H, Hansen H, Topcu O, Sardeli C, Wang W, Kwon TH, Nielsen S (2003) Renal aquaporins and sodium transporters with special focus on urinary tract obstruction. APMIS Suppl:71–79
19.
Frokiaer J, Marples D, Knepper MA, Nielsen S (1996) Bilateral ureteral obstruction downregulates expression of vasopressin-sensitive AQP-2 water channel in rat kidney. Am J Physiol 270:F657–F668PubMed
20.
Garofeanu CG, Weir M, Rosas-Arellano MP, Henson G, Garg AX, Clark WF (2005) Causes of reversible nephrogenic diabetes insipidus: a systematic review. Am J Kidney Dis 45:626–637PubMedCrossRef
21.
22.
Trachtman H (2009) Sodium and water. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds) Pediatr nephrol, 6th edn. Springer, Berlin Heidelberg New York, pp 159–184
23.
Sachs H, Takabatake Y (1964) Evidence for a precursor in vasopressin biosynthesis. Endocrinol 75:943–948CrossRef
24.
Nossent AY, Robben JH, Deen PM, Vos HL, Rosendaal FR, Doggen CJ, Hansen JL, Sheikh SP, Bertina RM, Eikenboom JC (2010) Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels. J Thromb Haemost 8:1547–1554PubMedCrossRef
25.
Loonen AJ, Knoers NV, van Os CH, Deen PM (2008) Aquaporin 2 mutations in nephrogenic diabetes insipidus. Semin Nephrol 28:252–265PubMedCrossRef
26.
Hendriks G, Koudijs M, van Balkom BW, Oorschot V, Klumperman J, Deen PM, van der Sluijs P (2004) Glycosylation is important for cell surface expression of the water channel aquaporin-2 but is not essential for tetramerization in the endoplasmic reticulum. J Biol Chem 279:2975–2983PubMedCrossRef
27.
Nielsen S, DiGiovanni SR, Christensen EI, Knepper MA, Harris HW (1993) Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA 90:11663–11667PubMedCrossRef
28.
Kamsteeg EJ, Heijnen I, van Os CH, Deen PM (2000) The subcellular localization of an aquaporin-2 tetramer depends on the stoichiometry of phosphorylated and nonphosphorylated monomers. J Cell Biol 151:919–930PubMedCrossRef
29.
Mandon B, Chou CL, Nielsen S, Knepper MA (1996) Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: possible role in aquaporin-2 trafficking. J Clin Invest 98:906–913PubMedCrossRef
30.
Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30PubMedCrossRef
31.
Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, Hirakawa M (2006) From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res 34:D354–D357PubMedCrossRef
32.
Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 38:D355–D360PubMedCrossRef
33.
Teng FY, Wang Y, Tang BL (2001) The syntaxins. Genome Biol 2:REVIEWS3012
34.
Nielsen S, Marples D, Birn H, Mohtashami M, Dalby NO, Trimble M, Knepper M (1995) Expression of VAMP-2-like protein in kidney collecting duct intracellular vesicles. Colocalization with Aquaporin-2 water channels. J Clin Invest 96:1834–1844PubMedCrossRef
35.
36.
Lee YJ, Kwon TH (2009) Ubiquitination of aquaporin-2 in the kidney. Electrolyte Blood Press 7:1–4PubMedCrossRef
37.
Vossenkamper A, Nedvetsky PI, Wiesner B, Furkert J, Rosenthal W, Klussmann E (2007) Microtubules are needed for the perinuclear positioning of aquaporin-2 after its endocytic retrieval in renal principal cells. Am J Physiol Cell Physiol 293:C1129–C1138PubMedCrossRef
38.
Marples D, Schroer TA, Ahrens N, Taylor A, Knepper MA, Nielsen S (1998) Dynein and dynactin colocalize with AQP2 water channels in intracellular vesicles from kidney collecting duct. Am J Physiol 274:F384–F394PubMed
39.
Palamidessi A, Frittoli E, Garre M, Faretta M, Mione M, Testa I, Diaspro A, Lanzetti L, Scita G, Di Fiore PP (2008) Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. Cell 134:135–147PubMedCrossRef
40.
Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10:513–525PubMedCrossRef
41.
Kamsteeg EJ, Hendriks G, Boone M, Konings IB, Oorschot V, van der Sluijs P, Klumperman J, Deen PM (2006) Short-chain ubiquitination mediates the regulated endocytosis of the aquaporin-2 water channel. Proc Natl Acad Sci USA 103:18344–18349PubMedCrossRef
42.
Klussmann E, Tamma G, Lorenz D, Wiesner B, Maric K, Hofmann F, Aktories K, Valenti G, Rosenthal W (2001) An inhibitory role of Rho in the vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells. J Biol Chem 276:20451–20457PubMedCrossRef
43.
Tajika Y, Matsuzaki T, Suzuki T, Ablimit A, Aoki T, Hagiwara H, Kuwahara M, Sasaki S, Takata K (2005) Differential regulation of AQP2 trafficking in endosomes by microtubules and actin filaments. Histochem Cell Biol 124:1–12PubMedCrossRef
44.
Yasui M, Zelenin SM, Celsi G, Aperia A (1997) Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. Am J Physiol 272:F443–F450PubMed
45.
Nielsen S, Kwon TH, Christensen BM, Promeneur D, Frokiaer J, Marples D (1999) Physiology and pathophysiology of renal aquaporins. J Am Soc Nephrol 10:647–663PubMed
46.
Blanchard A, Frank M, Wuerzner G, Peyrard S, Bankir L, Jeunemaitre X, Azizi M (2011) Antinatriuretic effect of vasopressin in humans is amiloride-sensitive, thus ENaC dependent. Clin J Am Soc Nephrol 6:753–759PubMedCrossRef
47.
48.
49.
Brown D, Katsura T, Gustafson CE (1998) Cellular mechanisms of aquaporin trafficking. Am J Physiol 275:F328–F331PubMed
50.
Sands JM, Bichet DG (2006) Nephrogenic diabetes insipidus. Ann Intern Med 144:186–194PubMed
51.
Birnbaumer M (2001) The V2 vasopressin receptor mutations and fluid homeostasis. Cardiovasc Res 51:409–415PubMedCrossRef
52.
van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA (1992) Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus. Nat Genet 2:99–102PubMedCrossRef
53.
Bichet DG (2008) Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin Nephrol 28:245–251PubMedCrossRef
54.
Nomura Y, Onigata K, Nagashima T, Yutani S, Mochizuki H, Nagashima K, Morikawa A (1997) Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation. J Clin Endocrinol Metab 82:3434–3437PubMedCrossRef
55.
Faerch M, Corydon TJ, Rittig S, Christensen JH, Hertz JM, Jendle J (2010) Skewed X-chromosome inactivation causing diagnostic misinterpretation in congenital nephrogenic diabetes insipidus. Scand J Urol Nephrol 44:324–330PubMedCrossRef
56.
Firsov D, Mandon B, Morel A, Merot J, Le Maout S, Bellanger AC, de Rouffignac C, Elalouf JM, Buhler JM (1994) Molecular analysis of vasopressin receptors in the rat nephron. Evidence for alternative splicing of the V2 receptor. Pflug Arch 429:79–89CrossRef
57.
Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, Martin MJ, Michoud K, O'Donovan C, Phan I, Pilbout S, Schneider M (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res 31:365–370PubMedCrossRef
58.
Brown CA, Black SD (1989) Membrane topology of mammalian cytochromes P-450 from liver endoplasmic reticulum. Determination by trypsinolysis of phenobarbital-treated microsomes. J Biol Chem 264:4442–4449PubMed
59.
Hartmann E, Rapoport TA, Lodish HF (1989) Predicting the orientation of eukaryotic membrane-spanning proteins. Proc Natl Acad Sci USA 86:5786–5790PubMedCrossRef
60.
Conner M, Hawtin SR, Simms J, Wootten D, Lawson Z, Conner AC, Parslow RA, Wheatley M (2007) Systematic analysis of the entire second extracellular loop of the V(1a) vasopressin receptor: key residues, conserved throughout a G-protein-coupled receptor family, identified. J Biol Chem 282:17405–17412PubMedCrossRef
61.
Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739–745PubMedCrossRef
62.
Sangkuhl K, Rompler H, Busch W, Karges B, Schoneberg T (2005) Nephrogenic diabetes insipidus caused by mutation of Tyr205: a key residue of V2 vasopressin receptor function. Hum Mutat 25:505PubMedCrossRef
63.
Oksche A, Schulein R, Rutz C, Liebenhoff U, Dickson J, Muller H, Birnbaumer M, Rosenthal W (1996) Vasopressin V2 receptor mutants that cause X-linked nephrogenic diabetes insipidus: analysis of expression, processing, and function. Mol Pharmacol 50:820–828PubMed
64.
Sadeghi H, Birnbaumer M (1999) O-Glycosylation of the V2 vasopressin receptor. Glycobiology 9:731–737PubMedCrossRef
65.
Robben JH, Knoers NV, Deen PM (2004) Regulation of the vasopressin V2 receptor by vasopressin in polarized renal collecting duct cells. Mol Biol Cell 15:5693–5699PubMedCrossRef
66.
Sarmiento JM, Anazco CC, Campos DM, Prado GN, Navarro J, Gonzalez CB (2004) Novel down-regulatory mechanism of the surface expression of the vasopressin V2 receptor by an alternative splice receptor variant. J Biol Chem 279:47017–47023PubMedCrossRef
67.
Gonzalez A, Borquez M, Trigo CA, Brenet M, Sarmiento JM, Figueroa CD, Navarro J, Gonzalez CB (2011) The splice variant of the V2 vasopressin receptor adopts alternative topologies. Biochem 50:4981–4986CrossRef
68.
69.
Thibonnier M, Preston JA, Dulin N, Wilkins PL, Berti-Mattera LN, Mattera R (1997) The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. Endocrinol 138:4109–4122CrossRef
70.
Vargas-Poussou R, Forestier L, Dautzenberg MD, Niaudet P, Dechaux M, Antignac C (1997) Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 8:1855–1862PubMed
71.
Spanakis E, Milord E, Gragnoli C (2008) AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. J Cell Physiol 217:605–617PubMedCrossRef
72.
73.
Krawczak M, Ball EV, Cooper DN (1998) Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. Am J Hum Genet 63:474–488PubMedCrossRef
74.
Wenkert D, Schoneberg T, Merendino JJ Jr, Rodriguez Pena MS, Vinitsky R, Goldsmith PK, Wess J, Spiegel AM (1996) Functional characterization of five V2 vasopressin receptor gene mutations. Mol Cell Endocrinol 124:43–50PubMedCrossRef
75.
Abaci A, Wood K, Demir K, Buyukgebiz A, Bober E, Kopp P (2010) A novel mutation in the AVPR2 gene (222delA) associated with X-linked nephrogenic diabetes insipidus in a boy with growth failure. Endocr Pract 16:231–236PubMedCrossRef
76.
Moon SD, Kim JH, Shim JY, Lim DJ, Cha BY, Han JH (2011) Analysis of a novel AVPR2 mutation in a family with nephrogenic diabetes insipidus. Int J Clin Exp Med 4:1–9PubMed
77.
Fujimoto M, Imai K, Hirata K, Kashiwagi R, Morinishi Y, Kitazawa K, Sasaki S, Arinami T, Nonoyama S, Noguchi E (2008) Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes. BMC Med Genet 9:42PubMedCrossRef
78.
Satoh M, Ogikubo S, Yoshizawa-Ogasawara A (2008) Correlation between clinical phenotypes and X-inactivation patterns in six female carriers with heterozygote vasopressin type 2 receptor gene mutations. Endocr J 55:277–284PubMedCrossRef
79.
Sakallioglu O, Tascilar ME, Kalman S, Cheong HI, Atay AA (2009) Nephrogenic diabetes insipidus due to a novel AVPR2 mutation. J Pediatr Endocrinol Metab 22:187–189PubMedCrossRef
80.
Ranadive SA, Ersoy B, Favre H, Cheung CC, Rosenthal SM, Miller WL, Vaisse C (2009) Identification, characterization and rescue of a novel vasopressin-2 receptor mutation causing nephrogenic diabetes insipidus. Clin Endocrinol (Oxf) 71:388–393CrossRef
81.
Vaisbich MH, Carneiro J, Boson W, Resende B, De ML, Honjo RS, Kim CA, Koch VH (2009) Nephrogenic diabetes insipidus (NDI): clinical, laboratory and genetic characterization of five Brazilian patients. Clinics(Sao Paulo) 64:409–414
82.
Takatani T, Matsuo K, Kinoshita K, Takatani R, Minagawa M, Kohno Y (2010) A novel missense mutation in the AVPR2 gene of a Japanese infant with nephrogenic diabetes insipidus. J Pediatr Endocrinol Metab 23:415–418PubMedCrossRef
83.
El-Kares R, Hueber PA, Blumenkrantz M, Iglesias D, Ma K, Jabado N, Bichet DG, Goodyer P (2009) Wilms tumor arising in a child with X-linked nephrogenic diabetes insipidus. Pediatr Nephrol 24:1313–1319PubMedCrossRef
84.
Sahakitrungruang T, Tee MK, Rattanachartnarong N, Shotelersuk V, Suphapeetiporn K, Miller WL (2010) Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families. Horm Res Paediatr 73:349–354PubMedCrossRef
85.
Oksche A, Dickson J, Schulein R, Seyberth HW, Muller M, Rascher W, Birnbaumer M, Rosenthal W (1994) Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus. Biochem Biophys Res Comm 205:552–557PubMedCrossRef
86.
Welsh MJ, Smith AE (1993) Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 73:1251–1254PubMedCrossRef
87.
Tsukaguchi H, Matsubara H, Taketani S, Mori Y, Seido T, Inada M (1995) Binding-, intracellular transport-, and biosynthesis-defective mutants of vasopressin type 2 receptor in patients with X-linked nephrogenic diabetes insipidus. J Clin Invest 96:2043–2050PubMedCrossRef
88.
Ala Y, Morin D, Mouillac B, Sabatier N, Vargas R, Cotte N, Dechaux M, Antignac C, Arthus MF, Lonergan M, Turner MS, Balestre MN, Alonso G, Hibert M, Barberis C, Hendy GN, Bichet DG, Jard S (1998) Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol 9:1861–1872PubMed
89.
Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S (1994) Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Hum Genet 55:278–286PubMed
90.
91.
Arthus MF, Lonergan M, Crumley MJ, Naumova AK, Morin D, De Marco LA, Kaplan BS, Robertson GL, Sasaki S, Morgan K, Bichet DG, Fujiwara TM (2000) Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 11:1044–1054PubMed
92.
Ellgaard L, Helenius A (2001) ER quality control: towards an understanding at the molecular level. Curr Opin Cell Biol 13:431–437PubMedCrossRef
93.
Oueslati M, Hermosilla R, Schonenberger E, Oorschot V, Beyermann M, Wiesner B, Schmidt A, Klumperman J, Rosenthal W, Schulein R (2007) Rescue of a nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutant by cell-penetrating peptides. J Biol Chem 282:20676–20685PubMedCrossRef
94.
Pan Y, Wilson P, Gitschier J (1994) The effect of eight V2 vasopressin receptor mutations on stimulation of adenylyl cyclase and binding to vasopressin. J Biol Chem 269:31933–31937PubMed
95.
Robben JH, Knoers NV, Deen PM (2006) Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 291:F257–F270PubMedCrossRef
96.
Barak LS, Oakley RH, Laporte SA, Caron MG (2001) Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus. Proc Natl Acad Sci USA 98:93–98PubMedCrossRef
97.
Knoers N, Monnens LA (1992) Nephrogenic diabetes insipidus: clinical symptoms, pathogenesis, genetics and treatment. Pediatr Nephrol 6:476–482PubMedCrossRef
98.
Bai L, Fushimi K, Sasaki S, Marumo F (1996) Structure of aquaporin-2 vasopressin water channel. J Biol Chem 271:5171–5176PubMedCrossRef
99.
Marr N, Bichet DG, Hoefs S, Savelkoul PJ, Konings IB, De MF, Graat MP, Arthus MF, Lonergan M, Fujiwara TM, Knoers NV, Landau D, Balfe WJ, Oksche A, Rosenthal W, Muller D, van Os CH, Deen PM (2002) Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus. J Am Soc Nephrol 13:2267–2277PubMedCrossRef
100.
Baumgarten R, Van De Pol MH, Wetzels JF, van Os CH, Deen PM (1998) Glycosylation is not essential for vasopressin-dependent routing of aquaporin-2 in transfected Madin-Darby canine kidney cells. J Am Soc Nephrol 9:1553–1559PubMed
101.
Fushimi K, Sasaki S, Marumo F (1997) Phosphorylation of serine 256 is required for cAMP-dependent regulatory exocytosis of the aquaporin-2 water channel. J Biol Chem 272:14800–14804PubMedCrossRef
102.
Hoffert JD, Pisitkun T, Wang G, Shen RF, Knepper MA (2006) Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites. Proc Natl Acad Sci USA 103:7159–7164PubMedCrossRef
103.
Hoffert JD, Fenton RA, Moeller HB, Simons B, Tchapyjnikov D, McDill BW, Yu MJ, Pisitkun T, Chen F, Knepper MA (2008) Vasopressin-stimulated increase in phosphorylation at Ser269 potentiates plasma membrane retention of aquaporin-2. J Biol Chem 283:24617–24627PubMedCrossRef
104.
Moeller HB, MacAulay N, Knepper MA, Fenton RA (2009) Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating. Am J Physiol Renal Physiol 296:F649–F657PubMedCrossRef
105.
Xie L, Hoffert JD, Chou CL, Yu MJ, Pisitkun T, Knepper MA, Fenton RA (2010) Quantitative analysis of aquaporin-2 phosphorylation. Am J Physiol Renal Physiol 298:F1018–F1023PubMedCrossRef
106.
Hoffert JD, Nielsen J, Yu MJ, Pisitkun T, Schleicher SM, Nielsen S, Knepper MA (2007) Dynamics of aquaporin-2 serine-261 phosphorylation in response to short-term vasopressin treatment in collecting duct. Am J physiology Renal Physiol 292:F691–F700CrossRef
107.
Moeller HB, Olesen ET, Fenton RA (2011) Regulation of the water channel aquaporin-2 by posttranslational modification. Am J Physiol Renal Physiol 300:F1062–F1073PubMedCrossRef
108.
Heymann JB, Engel A (1999) Aquaporins: Phylogeny, Structure, and Physiology of Water Channels. News Physiol Sci 14:187–193PubMed
109.
Hub JS, Grubmuller H, de Groot BL (2009) Dynamics and energetics of permeation through aquaporins. What do we learn from molecular dynamics simulations? Handb Exp Pharmacol 57–76
110.
de Groot BL, Grubmuller H (2001) Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science 294:2353–2357PubMedCrossRef
111.
Kozono D, Yasui M, King LS, Agre P (2002) Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine. J Clin Invest 109:1395–1399PubMed
112.
Murata K, Mitsuoka K, Hirai T, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y (2000) Structural determinants of water permeation through aquaporin-1. Nature 407:599–605PubMedCrossRef
113.
de Groot BL, Grubmuller H (2005) The dynamics and energetics of water permeation and proton exclusion in aquaporins. Curr Opin Struct Biol 15:176–183PubMedCrossRef
114.
Lin SH, Bichet DG, Sasaki S, Kuwahara M, Arthus MF, Lonergan M, Lin YF (2002) Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families. J Clin Endocrinol Metab 87:2694–2700PubMedCrossRef
115.
Boone M, Deen PM (2009) Congenital nephrogenic diabetes insipidus: what can we learn from mouse models? Exp Physiol 94:186–190PubMedCrossRef
116.
Lloyd DJ, Hall FW, Tarantino LM, Gekakis N (2005) Diabetes insipidus in mice with a mutation in aquaporin-2. PLoS Genet 1:e20PubMedCrossRef
117.
Tamarappoo BK, Verkman AS (1998) Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones. J Clin Invest 101:2257–2267PubMedCrossRef
118.
Abrami L, Berthonaud V, Deen PM, Rousselet G, Tacnet F, Ripoche P (1996) Glycerol permeability of mutant aquaporin 1 and other AQP-MIP proteins: inhibition studies. Pflug Arch 431:408–414CrossRef
119.
Goji K, Kuwahara M, Gu Y, Matsuo M, Marumo F, Sasaki S (1998) Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function. J Clin Endocrinol Metab 83:3205–3209PubMedCrossRef
120.
Kamsteeg EJ, Deen PM (2000) Importance of aquaporin-2 expression levels in genotype -phenotype studies in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 279:F778–F784PubMed
121.
Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (2001) Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus. J Biol Chem 276:2775–2779PubMedCrossRef
122.
Deen PM, van Balkom BW, Kamsteeg EJ (2000) Routing of the aquaporin-2 water channel in health and disease. Eur J Cell Biol 79:523–530PubMedCrossRef
123.
De Mattia F, Savelkoul PJ, Kamsteeg EJ, Konings IB, van der Sluijs P, Mallmann R, Oksche A, Deen PM (2005) Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus. J Am Soc Nephrol 16:2872–2880PubMedCrossRef
124.
Kamsteeg EJ, Bichet DG, Konings IB, Nivet H, Lonergan M, Arthus MF, van Os CH, Deen PM (2003) Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic diabetes insipidus. J Cell Biol 163:1099–1109PubMedCrossRef
125.
Kuwahara M, Iwai K, Ooeda T, Igarashi T, Ogawa E, Katsushima Y, Shinbo I, Uchida S, Terada Y, Arthus MF, Lonergan M, Fujiwara TM, Bichet DG, Marumo F, Sasaki S (2001) Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet 69:738–748PubMedCrossRef
126.
Marr N, Bichet DG, Lonergan M, Arthus MF, Jeck N, Seyberth HW, Rosenthal W, van Os CH, Oksche A, Deen PM (2002) Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus. Hum Mol Genet 11:779–789PubMedCrossRef
127.
Mulders SM, Bichet DG, Rijss JP, Kamsteeg EJ, Arthus MF, Lonergan M, Fujiwara M, Morgan K, Leijendekker R, van der Sluijs P, van Os CH, Deen PM (1998) An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. J Clin Invest 102:57–66PubMedCrossRef
128.
Savelkoul PJ, De MF, Li Y, Kamsteeg EJ, Konings IB, van der Sluijs P, Deen PM (2009) p.R254Q mutation in the aquaporin-2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin-induced phosphorylation. Hum Mutat 30:E891–E903PubMedCrossRef
129.
Shinbo I, Fushimi K, Kasahara M, Yamauchi K, Sasaki S, Marumo F (1999) Functional analysis of aquaporin-2 mutants associated with nephrogenic diabetes insipidus by yeast expression. Am J Physiol 277:F734–F741PubMed
130.
Kamsteeg EJ, Wormhoudt TA, Rijss JP, van Os CH, Deen PM (1999) An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus. EMBO J 18:2394–2400PubMedCrossRef
131.
Moon SS, Kim HJ, Choi YK, Seo HA, Jeon JH, Lee JE, Lee JY, Kwon TH, Kim JG, Kim BW, Lee IK (2009) Novel mutation of aquaporin-2 gene in a patient with congenital nephrogenic diabetes insipidus. Endocr J 56:905–910PubMedCrossRef
132.
van Lieburg AF, Verdijk MA, Knoers VV, van Essen AJ, Proesmans W, Mallmann R, Monnens LA, van Oost BA, van Os CH, Deen PM (1994) Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene. AmJ Hum Genet 55:648–652
133.
Asai T, Kuwahara M, Kurihara H, Sakai T, Terada Y, Marumo F, Sasaki S (2003) Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations. Kidney Int 64:2–10PubMedCrossRef
134.
van Balkom BW, Savelkoul PJ, Markovich D, Hofman E, Nielsen S, van der Sluijs P, Deen PM (2002) The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel. J Biol Chem 277:41473–41479PubMedCrossRef
135.
Lu HJ, Matsuzaki T, Bouley R, Hasler U, Qin QH, Brown D (2008) The phosphorylation state of serine 256 is dominant over that of serine 261 in the regulation of AQP2 trafficking in renal epithelial cells. Am J Physiol Renal Physiol 295:F290–F294PubMedCrossRef
136.
Moeller HB, MacAulay N, Knepper MA, Fenton RA (2009) Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating. Am J Physiol Renal Physiol 296:F649–F657PubMedCrossRef
137.
Kamsteeg EJ, Stoffels M, Tamma G, Konings IB, Deen PM (2009) Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus. Hum Mutat 30:1387–1396PubMedCrossRef
138.
Kamsteeg EJ, Savelkoul PJ, Hendriks G, Konings IB, Nivillac NM, Lagendijk AK, van der Sluijs P, Deen PM (2008) Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphorylation by PKC but is due to the loss of E258. Pflug Arch 455:1041–1054CrossRef
139.
Tajika Y, Matsuzaki T, Suzuki T, Aoki T, Hagiwara H, Tanaka S, Kominami E, Takata K (2002) Immunohistochemical characterization of the intracellular pool of water channel aquaporin-2 in the rat kidney. Anat Sci Int 77:189–195PubMedCrossRef
140.
Sohara E, Rai T, Yang SS, Uchida K, Nitta K, Horita S, Ohno M, Harada A, Sasaki S, Uchida S (2006) Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation. Proc Natl Acad Sci USA 103:14217–14222PubMedCrossRef
141.
Katsura T, Gustafson CE, Ausiello DA, Brown D (1997) Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells. Am J Physiol 272:F817–F822PubMed
142.
Edemir B, Pavenstadt H, Schlatter E, Weide T (2011) Mechanisms of cell polarity and aquaporin sorting in the nephron. Pflug Arch 461:607–621CrossRef
143.
McDill BW, Li SZ, Kovach PA, Ding L, Chen F (2006) Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. Proc Natl Acad Sci USA 103:6952–6957PubMedCrossRef
144.
Rojek A, Fuchtbauer EM, Kwon TH, Frokiaer J, Nielsen S (2006) Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proc Natl Acad Sci USA 103:6037–6042PubMedCrossRef
145.
Yang B, Zhao D, Qian L, Verkman AS (2006) Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion. Am J Physiol Renal Physiol 291:F465–F472PubMedCrossRef
146.
De Mattia F, Savelkoul PJ, Bichet DG, Kamsteeg EJ, Konings IB, Marr N, Arthus MF, Lonergan M, van Os CH, van der Sluijs P, Robertson G, Deen PM (2004) A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L. Hum Mol Genet 13:3045–3056PubMedCrossRef
147.
Deen PM (2007) Mouse models for congenital nephrogenic diabetes insipidus: what can we learn from them? Nephrol Dial Transplant 22:1023–1026PubMedCrossRef
148.
Kirchlechner V, Koller DY, Seidl R, Waldhauser F (1999) Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride. Arch Dis Child 80:548–552PubMedCrossRef
149.
Alon U, Chan JC (1985) Hydrochlorothiazide-amiloride in the treatment of congenital nephrogenic diabetes insipidus. Am J Nephrol 5:9–13PubMedCrossRef
150.
Knoers N, Monnens LA (1990) Amiloride-hydrochlorothiazide versus indomethacin-hydrochlorothiazide in the treatment of nephrogenic diabetes insipidus. J Pediatr 117:499–502PubMedCrossRef
151.
Knoers NV, Deen PM (2001) Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr Nephrol 16:1146–1152PubMedCrossRef
152.
Kim GH, Lee JW, Oh YK, Chang HR, Joo KW, Na KY, Earm JH, Knepper MA, Han JS (2004) Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. J Am Soc Nephrol 15:2836–2843PubMedCrossRef
153.
Loffing J, Kaissling B (2003) Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human. Am J Physiol Renal Physiol 284:F628–F643PubMed
154.
Los EL, Deen PM, Robben JH (2010) Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus. J Neuroendocrinol 22:393–399PubMedCrossRef
155.
Robben JH, Kortenoeven ML, Sze M, Yae C, Milligan G, Oorschot VM, Klumperman J, Knoers NV, Deen PM (2009) Intracellular activation of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus by nonpeptide agonists. Proc Natl Acad Sci USA 106:12195–12200PubMedCrossRef
156.
Li JH, Chou CL, Li B, Gavrilova O, Eisner C, Schnermann J, Anderson SA, Deng CX, Knepper MA, Wess J (2009) A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus. J Clin Invest 119:3115–3126PubMedCrossRef
157.
Cohen FE, Kelly JW (2003) Therapeutic approaches to protein-misfolding diseases. Nature 426:905–909PubMedCrossRef
158.
Eilers M, Schatz G (1986) Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria. Nature 322:228–232PubMedCrossRef
159.
Morello JP, Salahpour A, Laperriere A, Bernier V, Arthus MF, Lonergan M, Petaja-Repo U, Angers S, Morin D, Bichet DG, Bouvier M (2000) Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 105:887–895PubMedCrossRef
160.
Wuller S, Wiesner B, Loffler A, Furkert J, Krause G, Hermosilla R, Schaefer M, Schulein R, Rosenthal W, Oksche A (2004) Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors. J Biol Chem 279:47254–47263PubMedCrossRef
161.
Bernier V, Morello JP, Zarruk A, Debrand N, Salahpour A, Lonergan M, Arthus MF, Laperriere A, Brouard R, Bouvier M, Bichet DG (2006) Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 17:232–243PubMedCrossRef
162.
Robben JH, Sze M, Knoers NV, Deen PM (2007) Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 292:F253–F260PubMedCrossRef
163.
Bernier V, Lagace M, Lonergan M, Arthus MF, Bichet DG, Bouvier M (2004) Functional rescue of the constitutively internalized V2 vasopressin receptor mutant R137H by the pharmacological chaperone action of SR49059. Mol Endocrinol 18:2074–2084PubMedCrossRef
164.
Thibonnier M, Conarty DM, Preston JA, Wilkins PL, Berti-Mattera LN, Mattera R (1998) Molecular pharmacology of human vasopressin receptors. Adv Exp Med Biol 449:251–276PubMedCrossRef
165.
Jean-Alphonse F, Perkovska S, Frantz MC, Durroux T, Mejean C, Morin D, Loison S, Bonnet D, Hibert M, Mouillac B, Mendre C (2009) Biased agonist pharmacochaperones of the AVP V2 receptor may treat congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 20:2190–2203PubMedCrossRef
166.
Calebiro D, Nikolaev VO, Persani L, Lohse MJ (2010) Signaling by internalized G-protein-coupled receptors. Trends Pharmacol Sci 31:221–228PubMedCrossRef
167.
Calebiro D, Nikolaev VO, Lohse MJ (2010) Imaging of persistent cAMP signaling by internalized G protein-coupled receptors. J Mol Endocrinol 45:1–8PubMedCrossRef
168.
Calebiro D, Nikolaev VO, Gagliani MC, de FT, Dees C, Tacchetti C, Persani L, Lohse MJ (2009) Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol 7:e1000172
169.
Yun J, Schoneberg T, Liu J, Schulz A, Ecelbarger CA, Promeneur D, Nielsen S, Sheng H, Grinberg A, Deng C, Wess J (2000) Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene. J Clin Invest 106:1361–1371PubMedCrossRef
170.
Li Y, Shaw S, Kamsteeg EJ, Vandewalle A, Deen PM (2006) Development of lithium-induced nephrogenic diabetes insipidus is dissociated from adenylyl cyclase activity. J Am Soc Nephrol 17:1063–1072PubMedCrossRef
171.
Olesen ET, Rutzler MR, Moeller HB, Praetorius HA, Fenton RA (2011) Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus. Proc Natl Acad Sci USA 108:12949–12954PubMedCrossRef
172.
Desai S, April H, Nwaneshiudu C, Ashby B (2000) Comparison of agonist-induced internalization of the human EP2 and EP4 prostaglandin receptors: role of the carboxyl terminus in EP4 receptor sequestration. Mol Pharmacol 58:1279–1286PubMed
173.
174.
Steinwall M, Akerlund M, Bossmar T, Nishii M, Wright M (2004) ONO-8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women. BJOG 111:120–124PubMedCrossRef
175.
Yang B, Zhao D, Verkman AS (2009) Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation. FASEB J 23:503–512PubMedCrossRef
176.
Jiang C, Fang SL, Xiao YF, O'Connor SP, Nadler SG, Lee DW, Jefferson DM, Kaplan JM, Smith AE, Cheng SH (1998) Partial restoration of cAMP-stimulated CFTR chloride channel activity in DeltaF508 cells by deoxyspergualin. Am J Physiol 275:C171–C178PubMed
177.
Taiyab A, Sreedhar AS, Rao C (2009) Hsp90 inhibitors, GA and 17AAG, lead to ER stress-induced apoptosis in rat histiocytoma. Biochem Pharmacol 78:142–152PubMedCrossRef
178.
Wang W, Li C, Kwon TH, Knepper MA, Frokiaer J, Nielsen S (2002) AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors. Am J Physiol Renal Physiol 283:F1313–F1325PubMed
179.
Souness JE, Aldous D, Sargent C (2000) Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors. Immunopharmacol 47:127–162CrossRef
Metadaten
Titel
Congenital nephrogenic diabetes insipidus: the current state of affairs
verfasst von
Daniel Wesche
Peter M. T. Deen
Nine V. A. M. Knoers
Publikationsdatum
01.12.2012
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 12/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-012-2118-8

Weitere Artikel der Ausgabe 12/2012

Pediatric Nephrology 12/2012 Zur Ausgabe

Original Article

DNA methylation changes between relapse and remission of minimal change nephrotic syndrome

Brief Report

Eculizumab therapy in a child with hemolytic uremic syndrome and CFI mutation

Erratum

Erratum to: The phenomenon of focal segmental glomerulosclerosis post-transplantation—a one-hit wonder?

Original Article

Trends in pediatric primary membranoproliferative glomerulonephritis costs and complications

Abstracts

Abstracts for XXXVII Spanish Congress 2-4-June 2011 Barcelona

Original Article

TNFα pathway blockade ameliorates toxic effects of FSGS plasma on podocyte cytoskeleton and β3 integrin activation

Neu im Fachgebiet Pädiatrie

Neuer Typ-1-Diabetes bei Kindern am Wochenende eher übersehen

23.04.2024 Typ-1-Diabetes Nachrichten

Wenn Kinder an Werktagen zum Arzt gehen, werden neu auftretender Typ-1-Diabetes und diabetische Ketoazidosen häufiger erkannt als bei Arztbesuchen an Wochenenden oder Feiertagen.

Neue Studienergebnisse zur Myopiekontrolle mit Atropin

22.04.2024 Fehlsichtigkeit Nachrichten

Augentropfen mit niedrig dosiertem Atropin können helfen, das Fortschreiten einer Kurzsichtigkeit bei Kindern zumindest zu verlangsamen, wie die Ergebnisse einer aktuellen Studie mit verschiedenen Dosierungen zeigen.

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

18.04.2024 Spinale Muskelatrophien Nachrichten

Seit 2021 ist die Untersuchung auf spinale Muskelatrophie Teil des Neugeborenen-Screenings in Deutschland. Eine Studie liefert weitere Evidenz für den Nutzen der Maßnahme.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise