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Disease Profile

Nephrogenic diabetes insipidus

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

N25.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Diabetes insipidus nephrogenic; Diabetes insipidus nephrogenic type 1; Vasopressin-resistant diabetes insipidus;

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Metabolic disorders

Summary

Nephrogenic diabetes insipidus is a disorder in which a defect in the small tubes (tubules) in the kidneys causes a person to produce a large amount of urine. Nephrogenic diabetes insipidus occurs when the kidney tubules, which allow water to be removed from the body or reabsorbed, do not respond to a chemical in the body called antidiuretic hormone (ADH) or vasopressin.[1] ADH normally tells the kidneys to make the urine more concentrated. As a result of the defect, the kidneys release an excessive amount of water into the urine, producing a large quantity of very dilute urine.[2] The most common symptoms are frequent urination (polyuria), especially during nighttime (nocturia), and drinking too much liquids (polydipsia). It can be either acquired or hereditary. The acquired form is brought on by certain drugs and chronic diseases and can occur at any time during life. About 90% of all cases of hereditary nephrogenic diabetes insipidus result from mutations in the AVPR2 gene, and about 10% of cases are caused by mutations in the AQP2 gene.[3][4] Treatment consists of plenty of water intake; medication, such as thiazide diuretics and NSAIDs; and a low-salt, lowprotein diet.[5]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Nephrogenic diabetes insipidus
0009806
80%-99% of people have these symptoms
Hypernatremia
High blood sodium levels
0003228
Hypernatremic dehydration
0004906
Hyposthenuria
0003158
30%-79% of people have these symptoms
Anorexia
0002039
Constipation
0002019
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Fever
0001945
Nausea and vomiting
0002017
Polydipsia
Extreme thirst
0001959
5%-29% of people have these symptoms
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Hydroureter
0000072
Hypovolemia
Depleted blood volume
0011106
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Seizure
0001250
Short stature
Decreased body height
Small stature

[ more ]

0004322
1%-4% of people have these symptoms
Enuresis nocturna
0010677
Global developmental delay
0001263
Polyhydramnios
High levels of amniotic fluid
0001561
Percent of people who have these symptoms is not available through HPO
Diabetes insipidus
0000873
Feeding difficulties in infancy
0008872
Hypertonic dehydration
0001986
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Irritability
Irritable
0000737
Megacystis
0000021
Neonatal onset
0003623
Polyuria
Increased urine output
0000103
Unexplained fevers
0001955
Vomiting
Throwing up
0002013
X-linked recessive inheritance
0001419

Cause

Nephrogenic diabetes insipidus can be either acquired or hereditary. The acquired form can result from chronic kidney disease, certain medications (such as lithium), low levels of potassium in the blood (hypokalemia), high levels of calcium in the blood (hypercalcemia), or an obstruction of the urinary tract. Acquired nephrogenic diabetes insipidus can occur at any time during life.[3] 

The hereditary form of nephrogenic diabetes insipidus is caused by genetic mutations, and its signs and symptoms usually become apparent within the first few months of life.[3] The disease may be caused by mutations in two genesAVPR2 (about 90% of cases) and AQP2 (about 10% of cases).[3][4]

Diagnosis

Yes. GeneTests lists laboratories offering clinical genetic testing for both X-linked and autosomal types of nephrogenic diabetes insipidus. Clinical genetic tests are ordered to help diagnose a person or family and to aid in decisions regarding medical care or reproductive issues. Talk to your health care provider or a genetic professional to learn more about your testing options.

Treatment

Management is usually best accomplished by a team of physicians and other healthcare professionals. The team may include a nutritionist, a pediatric (or adult) nephrologist or endocrinologist, and a clinical geneticist.[4] 

The basis of management involves free access to drinking water and toilet facilities. The polyuria can be lowered with a low-salt (sodium), lowprotein diet; thiazide diuretics: hydrochlorothiazide and chlorothiazide; other diuretics (i.e., potassium-sparing diuretic amiloride); and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin. In babies, early recognition is very important because treatment can avoid the physical and intellectual disability that results from repeated episodes of dehydration and high levels of sodium (hypernatremia). Infants and very young children should be offered water every two hours during the day and night. In severe cases, continuous gastric feeding may be required. In adults, the decision to treat is based upon the individual patient's intolerance of the polyuria and polydipsia since, in almost all patients, the thirst mechanism is sufficient to maintain the sodium in the high-normal range. The medication desmopressin may be tried in patients who have persistent symptomatic polyuria after having the above described regimen. Several new approaches to treatment of this disorder are being investigated: V2 receptor chaperones and V2 receptor bypass.[4][6]

Management Guidelines

  • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Nephrogenic diabetes insipidus. This website is maintained by the National Library of Medicine.
        • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Nephrogenic diabetes insipidus. Click on the link to view a sample search on this topic.

            References

            1. Khardori R. Diabetes Insipidus. Medscape Reference. 2016; https://emedicine.medscape.com/article/117648-overview.
            2. Diabetes insipidus nephrogenic. Medlineplus. June 2010; https://www.nlm.nih.gov/medlineplus/ency/article/000511.htm.
            3. Nephrogenic diabetes insipidus. Genetics Home Reference. April 2010; https://ghr.nlm.nih.gov/condition/nephrogenic-diabetes-insipidus.
            4. Knoers N. Nephrogenic Diabetes Insipidus. GeneReviews. 2010; https://www.ncbi.nlm.nih.gov/books/NBK1177/.
            5. McMillan JI. Nephrogenic Diabetes Insipidus. Merck Manual. 2016; https://www.merckmanuals.com/professional/genitourinary-disorders/renal-transport-abnormalities/nephrogenic-diabetes-insipidus.
            6. Bichet DG. Treatment of nephrogenic diabetes insipidus. UpToDate. January 07, 2016; https://www.uptodate.com/contents/treatment-of-nephrogenic-diabetes-insipidus.

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