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Diabetes insipidus, nephrogenic, autosomal(NDI2)

MedGen UID:
289643
Concept ID:
C1563706
Disease or Syndrome
Synonyms: Diabetes insipidus, nephrogenic, 2, autosomal; NDI2; Nephrogenic Diabetes Insipidus, Type II
 
Gene (location): AQP2 (12q13.12)
 
Monarch Initiative: MONDO:0007451
OMIM®: 125800

Disease characteristics

Excerpted from the GeneReview: Hereditary Nephrogenic Diabetes Insipidus
Hereditary nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals. [from GeneReviews]
Authors:
Nine Knoers  |  Henny Lemmink   view full author information

Additional descriptions

From OMIM
Nephrogenic diabetes insipidus (NDI) is caused by the inability of the renal collecting ducts to absorb water in response to antidiuretic hormone (ADH), also known as arginine vasopressin (AVP; 192340). Approximately 90% of patients are males with the X-linked recessive form, type I (NDI1; 304800), which is caused by mutation in the gene encoding the vasopressin V2 receptor (AVPR2; 300538). The remaining 10% of patients have the autosomal form, type II (NDI2), caused by mutation in the AQP2 gene (Morello and Bichet, 2001). Neurogenic, or central, diabetes insipidus (CDI; 125700) is caused by mutation in the gene encoding arginine vasopressin, located on 20p13.  http://www.omim.org/entry/125800
From MedlinePlus Genetics
Arginine vasopressin resistance (previously called nephrogenic diabetes insipidus) is a disorder of water balance. The body normally balances fluid intake by releasing excess fluid in urine. However, people with arginine vasopressin resistance produce an excessive amount of urine (polyuria), which depletes the amount of water in the body. This water loss also leads to excessive thirst (polydipsia). 

Affected individuals can quickly become dehydrated if they do not drink enough water. Dehydration can cause dizziness and fatigue. Prolonged dehydration can lead to confusion, low blood pressure, seizures, and coma. People with arginine vasopressin resistance often develop high levels of sodium in the blood (hypernatremia) due to dehydration. Repeated cycles of dehydration can cause long-term health problems, particularly in children. 

Arginine vasopressin resistance can be either acquired or familial. The acquired form can occur at any time during life. The familial form usually become apparent within the first year of life, though in some cases they develop in adolescence or early adulthood.

Researchers have recommended using the condition name arginine vasopressin resistance because the previous name, nephrogenic diabetes insipidus, was often confused with a much more common disorder called diabetes mellitus. Arginine vasopressin resistance and diabetes mellitus are separate disorders with different features, causes, and treatment.

Infants with familial arginine vasopressin resistance tend to have problems feeding and gaining weight (failure to thrive). They may also be irritable and experience fevers, diarrhea, and vomiting. Recurrent episodes of dehydration can lead to slow growth and delayed development. If the condition is not well-managed, it can damage the bladder and kidneys leading to pain, infections, and kidney failure. With appropriate treatment, affected individuals usually have few complications and a normal lifespan.  https://medlineplus.gov/genetics/condition/arginine-vasopressin-resistance

Clinical features

From HPO
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Megacystis
MedGen UID:
343318
Concept ID:
C1855311
Finding
Dilatation of the bladder postnatally.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Polydipsia
MedGen UID:
43214
Concept ID:
C0085602
Sign or Symptom
Excessive thirst manifested by excessive fluid intake.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypernatremia
MedGen UID:
6966
Concept ID:
C0020488
Disease or Syndrome
An abnormally increased sodium concentration in the blood.
Hypertonic dehydration
MedGen UID:
205119
Concept ID:
C1112601
Disease or Syndrome
Unexplained fevers
MedGen UID:
337055
Concept ID:
C1844662
Finding
Episodes of fever for which no infectious cause can be identified.
Nephrogenic diabetes insipidus
MedGen UID:
57876
Concept ID:
C0162283
Disease or Syndrome
Hereditary nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Christ-Crain M, Winzeler B, Refardt J
J Intern Med 2021 Jul;290(1):73-87. Epub 2021 Mar 13 doi: 10.1111/joim.13261. PMID: 33713498
Refardt J
Best Pract Res Clin Endocrinol Metab 2020 Sep;34(5):101398. Epub 2020 Feb 28 doi: 10.1016/j.beem.2020.101398. PMID: 32387127
Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, Gallizia A, Rossi A, Maghnie M
Horm Res Paediatr 2012;77(2):69-84. Epub 2012 Mar 16 doi: 10.1159/000336333. PMID: 22433947

Curated

UK NICE Guideline NG19, Diabetic foot problems: prevention and management, 2019

Recent clinical studies

Etiology

Davis J, Desmond M, Berk M
BMC Nephrol 2018 Nov 3;19(1):305. doi: 10.1186/s12882-018-1101-4. PMID: 30390660Free PMC Article
Fotso Soh J, Torres-Platas SG, Beaulieu S, Mantere O, Platt R, Mucsi I, Saury S, Renaud S, Levinson A, Andreazza AC, Mulsant BH, Müller D, Schaffer A, Dols A, Cervantes P, Low NC, Herrmann N, Christensen BM, Trepiccione F, Rajji T, Rej S
BMC Psychiatry 2018 Jul 16;18(1):227. doi: 10.1186/s12888-018-1793-9. PMID: 30012135Free PMC Article
Baird-Gunning J, Lea-Henry T, Hoegberg LCG, Gosselin S, Roberts DM
J Intensive Care Med 2017 May;32(4):249-263. Epub 2016 Aug 11 doi: 10.1177/0885066616651582. PMID: 27516079
Laniado-Laborín R, Cabrales-Vargas MN
Rev Iberoam Micol 2009 Dec 31;26(4):223-7. doi: 10.1016/j.riam.2009.06.003. PMID: 19836985
Bendz H, Aurell M
Drug Saf 1999 Dec;21(6):449-56. doi: 10.2165/00002018-199921060-00002. PMID: 10612269

Diagnosis

Vaz de Castro PAS, Bitencourt L, de Oliveira Campos JL, Fischer BL, Soares de Brito SBC, Soares BS, Drummond JB, Simões E Silva AC
J Pediatr Endocrinol Metab 2022 Apr 26;35(4):421-434. Epub 2022 Feb 11 doi: 10.1515/jpem-2021-0566. PMID: 35146976
Christ-Crain M, Gaisl O
Presse Med 2021 Dec;50(4):104093. Epub 2021 Oct 27 doi: 10.1016/j.lpm.2021.104093. PMID: 34718110
Christ-Crain M, Winzeler B, Refardt J
J Intern Med 2021 Jul;290(1):73-87. Epub 2021 Mar 13 doi: 10.1111/joim.13261. PMID: 33713498
Refardt J, Winzeler B, Christ-Crain M
Endocrinol Metab Clin North Am 2020 Sep;49(3):517-531. Epub 2020 Jul 15 doi: 10.1016/j.ecl.2020.05.012. PMID: 32741486
Dabrowski E, Kadakia R, Zimmerman D
Best Pract Res Clin Endocrinol Metab 2016 Mar;30(2):317-28. Epub 2016 Feb 27 doi: 10.1016/j.beem.2016.02.006. PMID: 27156767

Therapy

Christ-Crain M, Gaisl O
Presse Med 2021 Dec;50(4):104093. Epub 2021 Oct 27 doi: 10.1016/j.lpm.2021.104093. PMID: 34718110
Mifsud S, Cilia K, Mifsud EL, Gruppetta M
Br J Hosp Med (Lond) 2020 Nov 2;81(11):1-9. Epub 2020 Nov 17 doi: 10.12968/hmed.2020.0457. PMID: 33263481
Kavanagh C, Uy NS
Pediatr Clin North Am 2019 Feb;66(1):227-234. doi: 10.1016/j.pcl.2018.09.006. PMID: 30454745
Dabrowski E, Kadakia R, Zimmerman D
Best Pract Res Clin Endocrinol Metab 2016 Mar;30(2):317-28. Epub 2016 Feb 27 doi: 10.1016/j.beem.2016.02.006. PMID: 27156767
Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, Gallizia A, Rossi A, Maghnie M
Horm Res Paediatr 2012;77(2):69-84. Epub 2012 Mar 16 doi: 10.1159/000336333. PMID: 22433947

Prognosis

Ilardi A
Diagnosis (Berl) 2022 Nov 1;9(4):403-410. Epub 2022 Aug 2 doi: 10.1515/dx-2022-0034. PMID: 35918296
Fotso Soh J, Torres-Platas SG, Beaulieu S, Mantere O, Platt R, Mucsi I, Saury S, Renaud S, Levinson A, Andreazza AC, Mulsant BH, Müller D, Schaffer A, Dols A, Cervantes P, Low NC, Herrmann N, Christensen BM, Trepiccione F, Rajji T, Rej S
BMC Psychiatry 2018 Jul 16;18(1):227. doi: 10.1186/s12888-018-1793-9. PMID: 30012135Free PMC Article
Bockenhauer D, Bichet DG
Curr Opin Pediatr 2017 Apr;29(2):199-205. doi: 10.1097/MOP.0000000000000473. PMID: 28134709
McIntyre RS, Mancini DA, Parikh S, Kennedy SH
Can J Psychiatry 2001 May;46(4):322-7. doi: 10.1177/070674370104600402. PMID: 11387787
Bendz H, Aurell M
Drug Saf 1999 Dec;21(6):449-56. doi: 10.2165/00002018-199921060-00002. PMID: 10612269

Clinical prediction guides

Fotso Soh J, Torres-Platas SG, Beaulieu S, Mantere O, Platt R, Mucsi I, Saury S, Renaud S, Levinson A, Andreazza AC, Mulsant BH, Müller D, Schaffer A, Dols A, Cervantes P, Low NC, Herrmann N, Christensen BM, Trepiccione F, Rajji T, Rej S
BMC Psychiatry 2018 Jul 16;18(1):227. doi: 10.1186/s12888-018-1793-9. PMID: 30012135Free PMC Article
Baird-Gunning J, Lea-Henry T, Hoegberg LCG, Gosselin S, Roberts DM
J Intensive Care Med 2017 May;32(4):249-263. Epub 2016 Aug 11 doi: 10.1177/0885066616651582. PMID: 27516079
Valenti G, Tamma G
G Ital Nefrol 2016 Feb;33 Suppl 66:33.S66.1. PMID: 26913870
Di Iorgi N, Napoli F, Allegri AE, Olivieri I, Bertelli E, Gallizia A, Rossi A, Maghnie M
Horm Res Paediatr 2012;77(2):69-84. Epub 2012 Mar 16 doi: 10.1159/000336333. PMID: 22433947
Robertson GL
Endocrinol Metab Clin North Am 1995 Sep;24(3):549-72. PMID: 8575409

Recent systematic reviews

Mu D, Ma Y, Cheng J, Qiu L, Chen S, Cheng X
Endocr Pract 2023 Aug;29(8):644-652. Epub 2023 May 22 doi: 10.1016/j.eprac.2023.05.006. PMID: 37225043
Schoot TS, Molmans THJ, Grootens KP, Kerckhoffs APM
Eur Neuropsychopharmacol 2020 Feb;31:16-32. Epub 2019 Dec 11 doi: 10.1016/j.euroneuro.2019.11.006. PMID: 31837914
Rej S, Pira S, Marshe V, Do A, Elie D, Looper KJ, Herrmann N, Müller DJ
Int Urol Nephrol 2016 Nov;48(11):1843-1853. Epub 2016 Jun 29 doi: 10.1007/s11255-016-1352-6. PMID: 27357223
Rej S, Herrmann N, Shulman K
J Geriatr Psychiatry Neurol 2012 Mar;25(1):51-61. doi: 10.1177/0891988712436690. PMID: 22467847
Garofeanu CG, Weir M, Rosas-Arellano MP, Henson G, Garg AX, Clark WF
Am J Kidney Dis 2005 Apr;45(4):626-37. doi: 10.1053/j.ajkd.2005.01.008. PMID: 15806465

Supplemental Content

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    Clinical resources

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    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2019
      UK NICE Guideline NG19, Diabetic foot problems: prevention and management, 2019

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