Nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor in Chief: Cafer Zorkun, M.D., Ph.D. [2]

Females heterozygous for X-linked NDI

Although an overnight urinary concentration test in female relatives was proposed as a method of carrier detection, it is unreliable.

Clinical Description

Natural History

Nephrogenic diabetes insipidus (NDI). Individuals with NDI typically have polyuria and polydipsia. However, in some infants, polydipsia and polyuria are often unappreciated or unimpressive. These infants may present with vomiting, gagging or retching, poor feeding, constipation or diarrhea, failure to thrive, unexplained fevers, and lethargy or irritability. The majority of affected individuals are diagnosed in the first year of life [van Lieburg et al 1999]. The initial symptoms in autosomal dominant NDI usually appear later, in some cases not before early adulthood.

Other infants, as well as older individuals, may present with rapid onset of severe dehydration associated with water deprivation, a hot environment, or intercurrent illnesses associated with decreased water intake and/or increased free water losses through vomiting, diarrhea, or fever. Seizures and/or coma may occur with rapid increases or decreases in plasma osmolality. Occasionally, the presenting sign is hydronephrosis, hydroureter, or megacystis.

Dehydrated individuals who have not been diagnosed to have NDI or who are unable to communicate their complaints run the risk of being improperly treated with IV administration of normal saline, especially in emergency situations. This may exacerbate hypernatremia. Prolonged, unrecognized, or repeated episodes of hypernatremic dehydration may result in seizures, permanent brain damage, developmental delay, and mental retardation. With early diagnosis and proper management, intelligence and life span are usually normal.

Chronic excretion of large volumes of urine in untreated persons results in hydronephrosis, hydroureter, and megacystis (huge bladder). Some degree of urinary tract distension may be seen on ultrasound examination even in infants [Yoo et al 2006].

Potential complications of urinary tract dilatation are rupture of the urinary tract, infection, intractable pain, improper bladder function, and/or kidney failure. These complications may occur as early as the second decade of life [Shalev et al 2004]. Lifestyle is substantially affected by the need to have constant access to potable water and by the increased frequency of urination. The unavailability of restroom facilities, even for a short time, is a problem in societies in which public urination is taboo. School and other social or group activities may be disrupted.

Affected individuals are almost always less than 50^th percentile for height; most are more than one standard deviation below the mean. Failure to thrive or short stature may result from unsuccessful management or inadequate nutrition related to polydipsia. Catch-up growth does not occur later in childhood [van Lieburg et al 1999].

Partial nephrogenic diabetes insipidus. Individuals with partial NDI tend to be diagnosed in later childhood. They usually do not have

Heterozygotes for X-linked NDI. Female carriers of X-linked NDI may have no symptoms or a variable degree of polyuria and polydipsia, or they may be as severely affected as males.

Genotype-Phenotype Correlations

X-linked and recessive NDI are similar with respect to initial symptoms and, with a few exceptions, age of onset.

In the minority of individuals with X-linked NDI and a V2 receptor mutation resulting in partial insensitivity to AVP or DDAVP, the disease onset may be later in childhood. Thus, three families had the missense mutation D85N associated with decreased ligand-binding affinity and decreased coupling to Gs, and one had the missense mutation G201D associated with a decreased number of cell surface AVPR2 receptors [Sadeghi et al 1997]. An individual representing a simplex case (a single affected individual in a family) had the mutation P322S, which was able to partly activate the Gs/adenylyl cyclase system [Ala et al 1998].

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with nephrogenic diabetes insipidus (NDI):

• Renal ultrasound examination to evaluate for hydronephrosis, dilatation of the urinary tract, and megacystis

Special situations

Individuals being prepared for surgery are often denied oral intake for many hours and are described as having 'NPO' (nothing per ora) status. In individuals with NDI, an IV must be provided from the beginning of NPO status, and the person's oral intake of water for that period, which is typically much larger than that of an individual who does not have NDI, should be given intravenously as 2.5% dextrose in water [Moug et al 2005].

Hydronephrosis, hydroureter, and megacystis

Treatment involves medical management to reduce urine output and continuous or intermittent bladder catheterization when significant post-void urinary bladder residuals are present.

Psychomotor development

Children with a history of an episode of severe dehydration, delayed developmental milestones, or a delay in establishing the correct diagnosis and management warrant a formal developmental evaluation and intervention before school age.

Surveillance

• Monitoring of growth in infants and children
• Periodic measurement of serum sodium concentration to identify unrecognized hyperosmolality and early dehydration. Note: Urine output and urine specific gravity are useless as indicators of hydration status.
• Annual renal ultrasound evaluation to monitor for hydronephrosis and megacystis [Shalev et al 2004]

Agents/Circumstances to Avoid

Restriction of water intake

Testing of Relatives at Risk

It is appropriate to evaluate at-risk infants as early as possible to allow for prompt diagnosis and treatment to reduce morbidity from hypernatremia, dehydration, and dilation of the urinary tract.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members.

Mode of Inheritance

Nephrogenic diabetes insipidus (NDI) may be transmitted in an X-linked recessive manner (90% of families), an autosomal recessive manner (~9% of families), or an autosomal dominant manner (~1% of families).

Risk to Family Members — X-Linked Inheritance

Parents of a proband

• The father of an affected male will not have NDI nor will he be a carrier of the mutation.

• Women who have an affected son and another affected male relative are obligate heterozygotes.

• A positive family history consistent with X-linked inheritance is observed in about half of X-linked cases [Arthus et al 2000].

• Pedigree analysis reveals that in about half of families with an affected male, he represents a simplex case (i.e., an affected individual with no known family history of NDI); several possibilities regarding his mother's carrier status need to be considered:

• The proband has a de novo disease-causing mutation in the AVPR2 gene and his mother is not a carrier;

• His mother has a de novo disease-causing mutation in the AVPR2 gene, either (a) as a "germline mutation" (i.e., present at the time of her conception and therefore in every cell of her body) or (b) as "germline mosaicism" (i.e., in some of her germ cells only);

• His maternal grandmother has a de novo disease-causing mutation in the AVPR2 gene.

Sibs of a proband

• The risk to sibs depends upon the genetic status of the proband's mother.

• If the mother of the proband has a disease-causing mutation, the chance of transmitting it in each pregnancy is 50%. Male sibs who inherit the mutation will be affected; female sibs who inherit the mutation will be carriers and will usually not be affected.

• If the disease-causing mutation cannot be detected in the DNA of the mother of the only affected male in the family, the risk to sibs is low but greater than that of the general population because the possibility of germline mosaicism exists.

Offspring of a proband

All the daughters of an affected male are carriers; none of his sons will be affected.

Carrier Detection

Carrier testing by molecular analysis of at-risk female relatives is available if the mutation has been identified in the proband.

Risk to Family Members — Autosomal Recessive Inheritance

Parents of a proband

• The parents are obligate heterozygotes and, therefore, carry a single copy of a disease-causing mutation in the AQP2 gene.
• Heterozygotes are asymptomatic.

Sibs of a proband

• At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
• Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3.
• Heterozygotes (carriers) are asymptomatic.

Offspring of a proband.

• The offspring of an individual with autosomal recessive NDI are obligate heterozygotes (carriers) for a disease-causing mutation in the AQP2 gene.

Other family members

Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier Detection

Carrier testing by molecular analysis for at-risk family members is available once the mutations have been identified in the proband.

Risk to Family Members — Autosomal Dominant Inheritance

Parents of a proband

• The proportion of individuals with autosomal dominant NDI who have an affected parent is unknown because the number of reported cases is small.

• A proband with autosomal dominant NDI may have the disorder as the result of a de novo gene mutation. The proportion of cases caused by de novo mutations is unknown.

Sibs of a proband

• The risk to sibs depends upon the genetic status of the proband's parent.

• If a parent of a proband is affected, the risk to the sibs is 50%.

• When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low.

Offspring of a proband

• Each child of an individual with autosomal dominant NDI has a 50% chance of inheriting the AQP2 mutation.

Other family members of a proband

• The risk to other family members depends upon the status of the proband's parents. If a parent is found to be affected, his or her family members are at risk.

Prenatal Testing

X-linked NDI. Prenatal testing is available for pregnancies at increased risk if the AVPR2 mutation has been identified in an affected family member. The usual procedure is to determine fetal sex by performing chromosome analysis on fetal cells obtained by chorionic villus sampling (CVS) at about ten to 12 weeks' gestation or by amniocentesis usually performed at about 15-18 weeks' gestation. If the karyotype is 46,XY, DNA from fetal cells can be analyzed for the known disease-causing mutation.

Autosomal recessive NDI. Prenatal diagnosis is available for pregnancies at increased risk. Analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15-18 weeks' gestation or chorionic villus sampling (CVS) at about ten to 12 weeks' gestation. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed. Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Requests for prenatal testing for conditions such as NDI that do not affect intellect and have treatment available are not common. Differences in perspective may exist among medical professionals and in families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, careful discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation(s) has/have been identified. Although technically feasible, PGD may be unacceptable and/or not allowed in some countries.

References

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. Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol. 1998; 9: 1861–72.

Albertazzi E, Zanchetta D, Barbier P, Faranda S, Frattini A, Vezzoni P, Procaccio M, Bettinelli A, Guzzi F, Parenti M, Chini B. Nephrogenic diabetes insipidus: functional analysis of new AVPR2 mutations identified in Italian families. J Am Soc Nephrol. 2000; 11: 1033–43.

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. Report of 33 novel AVPR2 mutations and analysis of 117 families with X- linked nephrogenic diabetes insipidus. J Am Soc Nephrol. 2000; 11: 1044–54.

Asai T, Kuwahara M, Kurihara H, Sakai T, Terada Y, Marumo F, Sasaki S. Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations. Kidney Int. 2003; 64: 2–10.

Bernier V, Lagace M, Lonergan M, Arthus MF, Bichet DG, Bouvier M. Functional rescue of the constitutively internalized V2 Vasopressin receptor mutant R137H by the pharmacological chaperone action of SR49059. Mol Endocrinol. 2004; 18: 2074–84.

Bernier V, Morello JP, Zarruk A, Debrand N, Salahpour A, Lonergan M, Arthus MF, Laperriere A, Brouard R, Bouvier M, Bichet DG. Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol. 2006; 17: 232–43.

Bichet DG. Nephrogenic diabetes insipidus. Am J Med. 1998; 105: 431–42.

Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S. et al. Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Hum Genet. 1994; 55: 278–86.

de Mattia F, Savelkoul PJ, Kamsteeg EJ, Konings IB, van der Sluijs P, Mallmann R, Oksche A, Deen PM. Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus. J Am Soc Nephrol. 2005; 16: 2872–80.

Feldman BJ, Rosenthal SM, Vargas GA, Fenwick RG, Huang EA, Matsuda-Abedini M, Lustig RH, Mathias RS, Portale AA, Miller WL, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005; 352: 1884–90.

Garofeanu CG, Weir M, Rosas-Arellano MP, Henson G, Garg AX, Clark WF. Causes of reversible nephrogenic diabetes insipidus: a systematic review. Am J Kidney Dis. 2005; 45: 626–37.

Inaba S, Hatakeyama H, Taniguchi N, Miyamori I. The property of a novel v2 receptor mutant in a patient with nephrogenic diabetes insipidus. J Clin Endocrinol Metab. 2001; 86: 381–5.

Iolascon A, Aglio V, Tamma G, D'Apolito M, Addabbo F, Procino G, Simonetti MC, Montini G, Gesualdo L, Debler EW, Svelto M, Valenti G. Characterization of two novel missense mutations in the AQP2 gene causing nephrogenic diabetes insipidus. Nephron Physiol. 2007; 105: 33–41.

Kamsteeg EJ, Bichet DG, Konings IB, Nivet H, Lonergan M, Arthus MF, van Os CH, Deen PM. Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic diabetes insipidus. J Cell Biol. 2003; 163: 1099–109.

Kamsteeg EJ, Wormhoudt TA, Rijss JP, van Os CH, Deen PM. An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus. EMBO J. 1999; 18: 2394–400.

Khanna A. Acquired nephrogenic diabetes insipidus. Semin Nephrol. 2006; 26: 244–8.

Kinoshita K, Miura Y, Nagasaki H, Murase T, Bando Y, Oiso Y. A novel deletion mutation in the arginine vasopressin receptor 2 gene and skewed X chromosome inactivation in a female patient with congenital nephrogenic diabetes insipidus. J Endocrinol Invest. 2004; 27: 167–70.

Knoers NV. Hyperactive vasopressin receptors and disturbed water homeostasis. N Engl J Med. 2005; 352: 1847–50.

Knoers NV, Deen PM. Aquaporin molecular biology and clinical abnormalities of the water transport channels. Curr Opin Pediatr. 1998; 10: 428–34.

Knoers NV, Monnens LL. Nephrogenic diabetes insipidus. Semin Nephrol. 1999; 19: 344–52.

Knoers NV, Deen PM. Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr Nephrol. 2001; 16: 1146–52.

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. Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet. 2001; 69: 738–48.

Lin SH, Bichet DG, Sasaki S, Kuwahara M, Arthus MF, Lonergan M, Lin YF. Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families. J Clin Endocrinol Metab. 2002; 87: 2694–700.

Marr N, Bichet DG, Hoefs S, Savelkoul PJ, Konings IB, De Mattia F, 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. Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus. J Am Soc Nephrol. 2002; 13: 2267–77.

Marr N, Bichet DG, Lonergan M, Arthus MF, Jeck N, Seyberth HW, Rosenthal W, van Os CH, Oksche A, Deen PM. 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. 2002; 11: 779–89.

Mizuno H, Fujimoto S, Sugiyama Y, Kobayashi M, Ohro Y, Uchida S, Sasaki S, Togari H. Successful treatment of partial nephrogenic diabetes insipidus with thiazide and desmopressin. Horm Res. 2003; 59: 297–300.

Morello JP, Bichet DG. Nephrogenic diabetes insipidus. Annu Rev Physiol. 2001; 63: 607–30.

Morello JP, Salahpour A, Laperriere A, Bernier V, Arthus MF, Lonergan M, Petaja-Repo U, Angers S, Morin D, Bichet DG, Bouvier M. Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest. 2000; 105: 887–95.

Moug SJ, McKee RF, O'Reilly DS, Noble S, Boulton-Jones M. The perioperative challenge of nephrogenic diabetes insipidus: a multidisciplinary approach. Surgeon. 2005; 3: 89–94.

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. An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. J Clin Invest. 1998; 102: 57–66.

Nomura Y, Onigata K, Nagashima T, Yutani S, Mochizuki H, Nagashima K, Morikawa A. Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation. J Clin Endocrinol Metab. 1997; 82: 3434–7.

Pasel K, Schulz A, Timmermann K, Linnemann K, Hoeltzenbein M, Jaaskelainen J, Gruters A, Filler G, Schoneberg T. Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families. J Clin Endocrinol Metab. 2000; 85: 1703–10.

Pattaragarn A, Alon US. Treatment of congenital nephrogenic diabetes insipidus by hydrochlorothiazide and cyclooxygenase-2 inhibitor. Pediatr Nephrol. 2003; 18: 1073–6.

Postina R, Ufer E, Pfeiffer R, Knoers NV, Fahrenholz F. Misfolded vasopressin V2 receptors caused by extracellular point mutations entail congential nephrogenic diabetes insipidus. Mol Cell Endocrinol. 2000; 164: 31–9.

Rittig S, Robertson GL, Siggaard C, Kovacs L, Gregersen N, Nyborg J, Pedersen EB. Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus. Am J Hum Genet. 1996; 58: 107–17.

Robben JH, Knoers NV, Deen PM. Characterization of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus in a polarized cell model. Am J Physiol Renal Physiol. 2005; 289: F265–72.

Robben JH, Sze M, Knoers NV, Deen PM. Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism. Mol Biol Cell. 2006; 17: 379–86.

Robertson GL. Differential diagnosis of polyuria. Annu Rev Med. 1988; 39: 425–42.

Robertson GL. Diabetes insipidus. Endocrinol Metab Clin North Am. 1995; 24: 549–72.

Sadeghi H, Robertson GL, Bichet DG, Innamorati G, Birnbaumer M. Biochemical basis of partial nephrogenic diabetes insipidus phenotypes. Mol Endocrinol. 1997; 11: 1806–13.

Schulz A, Sangkuhl K, Lennert T, Wigger M, Price DA, Nuuja A, Gruters A, Schultz G, Schoneberg T. Aminoglycoside pretreatment partially restores the function of truncated V(2) vasopressin receptors found in patients with nephrogenic diabetes insipidus. J Clin Endocrinol Metab. 2002; 87: 5247–57.

Shalev H, Romanovsky I, Knoers NV, Lupa S, Landau D. Bladder function impairment in aquaporin-2 defective nephrogenic diabetes insipidus. Nephrol Dial Transplant. 2004; 19: 608–13.

Sohara E, Rai T, Yang SS, Uchida K, Nitta K, Horita S, Ohno M, Harada A, Sasaki S, Uchida S. Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation. Proc Natl Acad Sci U S A. 2006; 103: 14217–22.

Soylu A, Kasap B, Ogun N, Ozturk Y, Turkmen M, Hoefsloot L, Kavukcu S. Efficacy of COX-2 inhibitors in a case of congenital nephrogenic diabetes insipidus. Pediatr Nephrol. 2005; 20: 1814–7.

Tajima T, Okuhara K, Satoh K, Nakae J, Fujieda K. Two novel aquaporin-2 mutations in a sporadic Japanese patient with autosomal recessive nephrogenic diabetes insipidus. Endocr J. 2003; 50: 473–6.

Tan CM, Nickols HH, Limbird LE. Appropriate polarization following pharmacological rescue of V2 vasopressin receptors encoded by X-linked nephrogenic diabetes insipidus alleles involves a conformation of the receptor that also attains mature glycosylation. J Biol Chem. 2003; 278: 35678–86.

van Balkom BW, Savelkoul PJ, Markovich D, Hofman E, Nielsen S, van der Sluijs P, Deen PM. The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel. J Biol Chem. 2002; 277: 41473–9.

van Lieburg AF, Knoers NV, Monnens LA. Clinical presentation and follow-up of 30 patients with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol. 1999; 10: 1958–64.

Wildin RS, Cogdell DE, Valadez V. AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus. Kidney Int. 1998; 54: 1909–22.

Yoo TH, Ryu DR, Song YS, Lee SC, Kim HJ, Kim JS, Choi HY, Kang SW. Congenital nephrogenic diabetes insipidus presented with bilateral hydronephrosis: genetic analysis of V2R gene mutations. Yonsei Med J. 2006; 47: 126–30.

Source

GeneReviews at NCBI (an article by Nine Knoers, MD)

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