Nephrogenic diabetes insipidus

Información en español Title

Other Names:

Diabetes insipidus nephrogenic; Diabetes insipidus nephrogenic type 1; Vasopressin-resistant diabetes insipidus; Diabetes insipidus nephrogenic; Diabetes insipidus nephrogenic type 1; Vasopressin-resistant diabetes insipidus; ADH resistant diabetes insipidus; Diabetes insipidus nephrogenic X-linked See More

Categories:

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

Summary 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, low-protein diet.^[5]

Last updated: 12/23/2016

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Nephrogenic diabetes insipidus	Obligate (present in 100% of cases)
Hypernatremia	Very frequent (present in 80%-99% of cases)
Hypernatremic dehydration	Very frequent (present in 80%-99% of cases)
Hyposthenuria	Very frequent (present in 80%-99% of cases)
Anorexia	Frequent (present in 30%-79% of cases)
Constipation	Frequent (present in 30%-79% of cases)
Failure to thrive	Frequent (present in 30%-79% of cases)
Fever	Frequent (present in 30%-79% of cases)
Nausea and vomiting	Frequent (present in 30%-79% of cases)
Polydipsia	Frequent (present in 30%-79% of cases)
Feeding difficulties	Occasional (present in 5%-29% of cases)
Hydroureter	Occasional (present in 5%-29% of cases)
Hypovolemia	Occasional (present in 5%-29% of cases)
Renal insufficiency	Occasional (present in 5%-29% of cases)
Seizures	Occasional (present in 5%-29% of cases)
Enuresis nocturna	Very rare (present in 1%-4% of cases)
Polyhydramnios	Very rare (present in 1%-4% of cases)
Diabetes insipidus	-
Feeding difficulties in infancy	-
Heterogeneous	-
Hypertonic dehydration	-
Intellectual disability	-
Irritability	-
Megacystis	-
Neonatal onset	-
Polyuria	-
Unexplained fevers	-
Vomiting	-
X-linked recessive inheritance	-

Last updated: 7/1/2017

Cause 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 genes, AVPR2 (about 90% of cases) and AQP2 (about 10% of cases).^[3]^[4]

Last updated: 12/23/2016

Inheritance Inheritance

When nephrogenic diabetes insipidus results from mutations in the AVPR2 gene (about 90% of the inherited cases of nephrogenic diabetes insipidus) the condition has an X-linked recessive pattern of inheritance.^[4] The AVPR2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually has to occur in both copies of the gene to cause the disorder. However, some females who carry a single mutated copy of the AVPR2 gene have features of nephrogenic diabetes insipidus, including polyuria and polydipsia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.^[3]

When nephrogenic diabetes insipidus is caused by mutations in the AQP2 gene (about 10% of the inherited cases of nephrogenic diabetes insipidus), it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance.^[4] In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In autosomal dominant inheritance, one mutated copy of the AQP2 gene in each cell is sufficient to cause the disorder.^[3]

Last updated: 12/23/2016

Diagnosis 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.

Last updated: 7/31/2011

Treatment 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), low-protein 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]

Last updated: 12/23/2016

Management Guidelines

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.
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.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Nephrogenic diabetes insipidus. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their 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

Histiocytosis Association of America
332 North Broadway
Pitman, NJ 08071
Toll-free: 800-548-2758
Telephone: 856-589-6606
Fax: 856-589-6614
Website: http://www.histio.org/
National Kidney Foundation
30 East 33rd Street
New York, NY 10016
Toll-free: 800-622-9010
Telephone: 212-889-2210
Fax: 212-689-9261
E-mail: http://www.kidney.org/about/contact.cfm
Website: http://www.kidney.org
Nephrogenic Diabetes Insipidus Foundation
P.O. Box 1390
Eastsound, WA 98245
Telephone: 888-376-6343
Fax: 888-376-6356
E-mail: info@ndif.org
Website: http://www.ndif.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More 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

Genetics Home Reference (GHR) contains information on Nephrogenic diabetes insipidus. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
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

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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My 14 year old son was diagnosed with nephrogenic diabetes insipidus 7 years ago. He has been taking indomethacin and hydrochlorothiazide and his urine output is fairly well controlled. Recently he developed gout in his big toe. His rheumatologist thinks that it may be due to the thiazide so he was switched to amiloride. Unfortunately, his symptoms got worse so he was put back on indomethacin and hydrochlorothiazide. What causes this condition? How is it inherited? How it it diagnosed? What treatments are available? Will he need to take medication for the rest of his life? See answer

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