What Is Nephrogenic Diabetes Insipidus?

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Nephrogenic diabetes insipidus (NDI) is a rare condition that affects fluid balance in the kidneys. NDI is caused by a problem with the vasopressin receptors in the kidneys. Vasopressin, also called antidiuretic hormone (ADH), is a hormone that decreases urine output by increasing the amount of water your kidneys absorb.

In NDI, the kidneys do not respond normally to vasopressin, so they produce too much urine (polyuria). As a result, a person with NDI passes abnormally large volumes of diluted urine, causing them to become dehydrated and excessively thirsty (polydipsia).

This article covers the causes and symptoms of NDI. It also details how NDI is diagnosed and treated, along with the complications that can arise from it.

doctor talking to patient

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Symptoms of Nephrogenic Diabetes Insipidus

The two main symptoms of NDI are:

  • Excessive urination, also known as polyuria
  • Excessive thirst, also known as polydipsia

If the fluid lost through your urine is not replaced (e.g. by drinking extra fluids), you can develop electrolyte imbalances. Symptoms of this include:

  • Unexplained weakness
  • Lethargy
  • Muscle cramps, twitches, and numbness
  • Irritability
  • Abdominal cramping
  • Dry mouth

Having NDI also puts you at a higher risk of dehydration, since your body cannot conserve water. Warning signs of dehydration include:

  • Increased thirst
  • Dry skin
  • Fatigue
  • Sluggishness
  • Dizziness
  • Confusion
  • Nausea

Under normal circumstances, a person will produce less than 3 liters of urine per day. A person with NDI, however, can produce between 3 and 15 liters of urine per day, and will need to drink large amounts of water to stay hydrated.


There are two types of nephrogenic diabetes insipidus:

  • Acquired NDI is brought on by certain drugs and chronic diseases. This type can occur at any time in life.
  • Hereditary NDI results from genetic mutations that impact the kidneys' ability to conserve water. Signs and symptoms of hereditary NDI are often seen in babies within the first few months of life.

Note that, while diabetes insipidus sounds like diabetes mellitus, the two conditions are not related.

Acquired NDI

Conditions that can trigger acquired NDI include:

It's also possible to develop NDI in pregnancy (gestational NDI). This can happen when an enzyme made by the placenta breaks down the mother's vasopressin.

Hereditary NDI

Most cases of hereditary NDI are due to X-linked genetic disorders. X-linked genetic disorders are caused by inheriting a nonworking gene on the X chromosome.

Because males have only one X chromosome and females have two, if a male inherits from his mother this recessive X-linked nonworking gene, he has a high chance of developing NDI. Females, on the other hand, can be carriers but cannot get hereditary NDI.


Nephrogenic diabetes insipidus can result from inherited gene changes, or mutations, that prevent the kidneys from responding to vasopressin.

That said, the vast majority of NDI cases are caused by:

  • Chronic kidney disease
  • Certain medications, particularly lithium
  • Low potassium levels in the blood
  • High calcium levels in the blood
  • Blockage of the urinary tract
  • Pregnancy

Sometimes, the causes of NDI are unknown, or idiopathic.


In order to make a diagnosis of NDI, your healthcare provider will start by asking you about your medical and family history. They will also perform a physical exam to check for signs of dehydration.

To help them form their diagnosis, they will typically order lab tests, beginning with a urinalysis. A sample of your urine will be collected and sent to a lab where a technician will measure how watery your urine is.

Your healthcare provider may order a blood test to measure sodium levels in your blood along with other substances that can reveal what type of NDI you have.

A fluid deprivation test helps confirm an NDI diagnosis. You will not be able to drink any fluids over the course of several hours, and your healthcare provider will take multiple samples of your urine. They will regularly measure your weight and check for changes in your urine and the electrolyte levels in your blood during the test.

Your healthcare provider may order magnetic resonance imaging (MRI), which uses magnets and radio waves to take detailed images of your brain tissues. The images can show your healthcare provider if there is any damage to your hypothalamus or pituitary gland that could cause NDI.

Finally, you may need to do a stimulation test, which can show your healthcare provider how your body reacts to vasopressin. For this test, you will be given an intravenous (IV) solution that stimulates your body to make vasopressin.


In some cases, NDI may go away after treatment, like switching medications or taking steps to balance the amount of calcium or potassium in your body. 

Diuretics—sometimes combined with aspirin or ibuprofen—may be helpful in managing symptoms. Diuretics help the kidneys remove fluid from the body, while aspirin or ibuprofen can reduce urine volume.

Thiazide diuretics are especially useful because they decrease urine production, which allows the kidneys to concentrate urine more effectively.


The outcomes for NDI are usually positive. The main complication is dehydration if fluid loss is greater than fluid intake. But dehydration is usually corrected by drinking more water.

Of note, infants and adults with NDI may become dehydrated rapidly following low water intake, being in a hot environment, or having another illness in addition to NDI.

Noticing the early signs of dehydration in infants is especially important to diagnose hereditary NDI. Infants may experience repeated episodes of dehydration, which can result in:

  • Dry or sticky mouth
  • Few or no tears when crying
  • Eyes that look sunken
  • Dry skin or mucus membranes
  • Weakness, dizziness, drowsiness, or confusion
  • Weight loss

Severe complications like seizures, brain damage, developmental delays, and physical and mental disability can develop if dehydration is left untreated in an infant. However, with proper diagnosis and prompt treatment, intelligence and development are usually normal.

Is There a Cure for NDI?

There is no cure for hereditary forms of NDI. For acquired NDI, properly managing the underlying cause will likely resolve your symptoms. For example, if you stop taking the medication causing your NDI, your NDI-induced symptoms should clear up.


Nephrogenic diabetes insipidus (NDI) occurs when your kidneys do not respond normally to the hormone vasopressin. NDI causes excessive thirst and urination. Unless the lost fluids are replaced, NDI can quickly lead to dehydration.

Whereas congenital NDI is caused by inherited gene mutations, acquired NDI can be triggered by conditions like chronic kidney disease or bad reactions to certain drugs like lithium. NDI is treated by drinking extra water to prevent dehydration. Thiazide diuretics may also be prescribed to decrease the kidneys' urine production.

A Word From Verywell

While there is no cure for inherited forms of NDI, the condition is often well managed by drinking enough liquid to prevent dehydration. Checking in with a healthcare professional, paying attention to your symptoms, and letting someone you trust know of the symptoms to look out for if you are not feeling well contribute to NDI's encouraging prognosis.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Shamard Charles, MD, MPH
Shamard Charles, MD, MPH is a public health physician and journalist. He has held positions with major news networks like NBC reporting on health policy, public health initiatives, diversity in medicine, and new developments in health care research and medical treatments.