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Nephrogenic diabetes insipidus (NDI) is a rare disorder that occurs when the kidneys are unable to concentrate urine. In most people, the body balances the fluids you drink with the amount of urine you excrete, or expel, from your body. However, people with NDI produce excessive amounts of urine. This is a condition known as polyuria and it causes insatiable thirst, or polydipsia.
NDI occurs when the balance between fluid intake and urine excretion is disrupted. NDI can cause dehydration, among other complications, so it’s important to talk to a doctor if you’re experiencing symptoms. NDI can be fatal if you don’t get treatment for it. The earlier you receive the diagnosis, the better your outlook will be.
NDI is unrelated to diabetes mellitus, which is more commonly known as diabetes.
The symptoms of NDI vary with age. Infants are severely affected, but the symptoms can resemble many other disorders. As children age, the symptoms become more recognizable. If a diagnosis isn’t made, the symptoms can become severe enough to be life-threatening. You should visit your doctor as soon as possible if you’re experiencing symptoms of NDI.
The symptoms in infants can include:
The symptoms in young children can include:
Older children and teenagers can display symptoms that include:
The most common symptoms experienced by adults include:
Rare and potentially fatal symptoms include hypovolemic shock and hypernatremic seizures.
Hypovolemic shock can occur when severe dehydration results in there not being enough blood for your heart to pump. This condition may result in death if you don’t get treatment for it.
Hypernatremic seizures occur when there are extremely high levels of sodium in the blood due to a lack of water in the body. This condition may result in death if you don’t get treatment for it.
The balance between fluid intake and urine excretion in the body is regulated by a hormone called vasopressin, or antidiuretic hormone (ADH). When fluid intake is low, the body’s levels of ADH increase and signal the kidneys to make less urine. On the other hand, when fluid intake is high, ADH levels decrease and cause the kidneys to create more urine. Waste and excess water in the blood are filtered through the kidneys, which then store liquid waste, or urine, in the bladder.
When ADH doesn’t work normally, whether because of a medical condition, medication, or genetics, your kidneys don’t concentrate your urine correctly. This means that you’ll urinate too much water out of your body. A variety of factors can affect your body’s regulation of ADH and cause NDI.
NDI can either be acquired or genetic, depending on what’s causing it.
Acquired NDI results from either the use of certain medications or having certain medical conditions. Most acquired forms of NDI stem from medication use. Medications that can cause acquired NDI include:
Certain medical conditions that affect minerals in the body or cause organ damage are also linked to NDI. These medical conditions interfere with the normal functioning of ADH and can cause acquired NDI. Conditions that can lead to NDI include:
Pregnancy is also a possible cause.
Mild forms can also occur in older adults, in those who are sick, and in people with acute kidney disease because the body can’t concentrate urine as well under these conditions. Acquired NDI is more common in adults than in children.
Genetic NDI occurs due to genetic mutations, which are passed down through families. Mutations are mistakes or damage that cause a change in the genes of a person. These mutations can interfere with the normal functioning of ADH.
Genetic NDI is occurs due to a mutation in either AVPR2 or AQP2. About 90 percent of cases of inherited NDI are due to mutations in the AVPR2 gene.
Mutations of the AVPR2 gene are X-linked recessive disorders. This means that the gene defect is on the X chromosome. Males have only one X chromosome. If they inherit an X chromosome with the gene mutation from their mother, they’ll have the disease. Because females have two X chromosomes, they’ll only acquire the disease if both of their X chromosomes have the gene mutation.
A smaller percentage of genetic NDI is caused by mutations in the AQP2 gene, which can be either autosomal recessive or dominant. Autosomal recessive means a person must receive a copy of the abnormal gene from each parent in order to develop NDI. More rarely, AQP2 is autosomal dominant, meaning that having one copy of the mutant gene can cause NDI.
Genetic NDI tends to be diagnosed in children.
It’s important to get an early diagnosis of NDI to prevent life-threatening complications. The tests will determine if your kidneys are doing a good job of maintaining the right amount of fluid in your body by regulating the volume and concentration of your urine. The symptoms of NDI make diagnosis difficult in childhood. Doctors use urine and blood tests to help them make a diagnosis.
The types of urine tests include the following:
Other tests for NDI include:
Your doctor may also recommend a water deprivation test. Only knowledgeable medical teams perform this test since it’s potentially life-threatening. The test involves refraining from drinking water to see if there’s any change in the amount of urine you release.
In acute and acquired forms of NDI, treatment often focuses on correcting the underlying cause, such as discontinuing a medication that caused NDI. In other cases, medications regulate the thirst mechanism and amount of urine released.
The first line of treatment is often a change in diet. Doctors will usually recommend a low-sodium, low-protein diet to adults. These diet changes should help reduce the urine output.
If diet changes don’t help reduce your urine output, your doctor may recommend medications:
Desmopressin is a synthetic form of ADH that can be used to treat nongenetic NDI.
NSAIDs and thiazide diuretics can help treat NDI. However, both medications are considered off-label drug use. Off-label drug use means that a drug that’s been approved by the FDA for one purpose is used for a different purpose that has not been approved. However, a doctor can still use the drug for that purpose. This is because the FDA regulates the testing and approval of drugs, but not how doctors use drugs to treat their patients. So, your doctor can prescribe a drug however they think is best for your care.
Diuretics and NSAIDs act by different mechanisms to increase the amounts of sodium and water that are reabsorbed by the kidney. These changes decrease the volume of urine.
Diuretics can help regulate how much water is excreted from your body in urine. Thiazide diuretics act by increasing the amount of water and sodium reabsorbed by the kidney, which decreases the volume of urine.
NSAIDS, such as indomethacin, can reduce urine output in people with NDI.
If you have a severe case of NDI, you may need intravenous (IV) hydration. You may also receive IV replenishment of 5 percent glucose, which is fluid with sugar added.
If your child has NDI, your doctor will usually recommend a low-sodium diet, but not a low-protein diet. Infants with NDI should be monitored carefully, because their small bodies don’t have much fluid to begin with. Infants with NDI should get water regularly and in between feedings to help prevent dehydration.
Children who have NDI and don’t get treated for it may not grow appropriately. In severe cases, they may experience developmental delays and intellectual disability from constant dehydration.
Without treatment, NDI can lead to death from dehydration complications. The outlook is good for those who receive treatment, and medications can help keep your health stable.
Written by: Lydia Krause
Medically reviewed on: Dec 15, 2016: University of Illinois-Chicago, School of Medicine
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