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Genetic and Rare Diseases Information Center (GARD)

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Nephrogenic diabetes insipidus

Other Names for this Disease
  • ADH resistant diabetes insipidus
  • Diabetes insipidus nephrogenic
  • Diabetes insipidus nephrogenic type 1
  • Diabetes insipidus nephrogenic X-linked
  • Vasopressin-resistant diabetes insipidus
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Your 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?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What causes nephrogenic diabetes insipidus?

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. 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.[1]
Last updated: 7/31/2011

What genes play a role in nephrogenic diabetes insipidus?

The hereditary form of nephrogenic diabetes insipidus can be caused by mutations in at least two genes. About 90 percent of all cases of hereditary nephrogenic diabetes insipidus result from mutations in the AVPR2 gene. Most of the remaining 10 percent of cases are caused by mutations in the AQP2 gene. Both of these genes provide instructions for making proteins that help determine how much water is excreted in urine.[1]
Last updated: 7/31/2011

How is nephrogenic diabetes insipidus inherited?

When nephrogenic diabetes insipidus results from mutations in the AVPR2 gene, the condition has an X-linked recessive pattern of inheritance. 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.[1]

When nephrogenic diabetes insipidus is caused by mutations in the AQP2 gene, it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance. 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.[1]

Last updated: 7/31/2011

Is genetic testing available for nephrogenic diabetes insipidus?

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

What if my son's genetic testing comes back normal?

If your son does not have a mutation in the AVPR2 or AQP2 genes, his condition may be due to another underlying cause. A careful evaluation should be done to rule out chronic renal insufficiency, lithium toxicity, hypercalcemia, hypokalemia, and/or obstructions in the urinary tract.[1][2]
Last updated: 7/31/2011

How might nephrogenic diabetes insipidus be treated?

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. The basis of management involves free access to drinking water and toilet facilities. Polyuria and polydipsia can be reduced up to 50% without disrupting appropriate levels of sodium in the blood through the use of thiazide diuretics hydrochlorothiazide, chlorothiazide) and/or other diuretics (i.e., potassium-sparing diuretic amiloride), dietary restriction of sodium, and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, which can potentially improve the ability of the body to concentrate urine and reduce urine output.[3]
Last updated: 7/31/2011

Will my son need to take medication to treat nephrogenic diabetes insipidus for the rest of his life?

This depends of the underlying cause of your son's condition. If the condition is due to a certain medication, stopping the medicine may improve symptoms. This decision needs to be made with the help of a physician. Nephrogenic diabetes insipidus that is present at birth or is due to an inherited mutation is a chronic condition requiring lifelong treatment.[4]
Last updated: 7/31/2011