What Is Nephrogenic Diabetes Insipidus?

Nephrogenic diabetes insipidus (NDI) is a rare condition that affects fluid balance in the kidneys. In NDI, kidneys dilute the urine too much because they are unable to control the concentration of urine due to the defective functioning of a hormone.

NDI is caused by defective vasopressin—also known as antidiuretic hormone (ADH)—receptors in two parts of the kidneys called the distal tubules and the collecting ducts.

NDI occurs when the kidneys do not respond normally to vasopressin and they produce too much urine (polyuria), causing a person to become excessively thirsty. As a result, people will pass an abnormally large volume of diluted and odorless urine.

If left untreated, this massive fluid loss can lead to severe dehydration, resulting in serious complications.

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 is not replaced, it can cause electrolyte imbalances, which include symptoms of:

• Unexplained weakness
• Lethargy
• Muscle pains
• Irritability

The body’s inability to conserve water can also put you at higher risk of becoming dehydrated. Warning signs of dehydration include:

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

Excessive water loss in the urine can be between 10 and 15 liters a day. So, drinking large amounts of water is vital to staying hydrated.

Types

The two types of NDI are:

• Acquired NDI, which is brought on by certain drugs and chronic diseases and can occur at any time during life
• Hereditary NDI, whose signs and symptoms are seen in babies, oftentimes within the first few months, as a result of genetic mutations that impact the kidneys' ability to conserve water

Acquired NDI

NDI may be acquired in a number of ways, including:

• A bad reaction to medications such as lithium or demeclocycline
• Prolonged metabolic imbalances such as low levels of potassium (hypokalemia) or high levels of calcium in the blood (hypercalcemia)
• Kidney disease (e.g., autosomal dominant polycystic kidney disease, renal amyloidosis)
• Blockage of the ureters (the tubes that carry urine from the kidneys to the bladder)
• Pregnancy. Gestational NDI (NDI that occurs in pregnancy) happens for one of two reasons. In some cases, an enzyme made by the placenta—a temporary organ joining mother and baby—breaks down the mother's vasopressin. In other cases, pregnant people produce more prostaglandin, a hormone-like chemical that reduces kidney sensitivity to 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 men have only one X chromosome and women have two, if a male inherits from his mother this recessive X-linked nonworking gene, he has a high chance of developing this disease. Women, on the other hand, can be carriers but cannot get this hereditary condition.

Causes 

Nephrogenic diabetes insipidus can result from inherited gene changes, or mutations, that prevent the kidneys from responding to vasopressin, but the overwhelming majority of causes are due to:

• 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

The causes of NDI may also be unknown, or idiopathic.

Diagnosis 

The diagnosis of NDI is made based on your history of symptoms and confirmatory tests performed by your practitioner or another healthcare provider. Diagnosis of NDI is made from the following:

• Medical and family history
• Physical exam
• Urinalysis
• Blood tests
• Fluid deprivation test
• Magnetic resonance imaging (MRI)

Treatment 

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.

Prognosis

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

Of note, infants and adults with NDI may rapidly develop dehydration following low water intake, being in a hot environment, or having a concurrent illness. 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:

• Weakness
• Confusion
• Dry mucus membranes
• Dry skin
• Weight loss

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

A Word From Verywell

If you have a mild case of nephrogenic diabetes insipidus, the only treatment is to drink more water. Changing your diet, such as by reducing salt, and drug therapy, such as using diuretics, may also help decrease urine output.

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 a family member or friend know of the symptoms to look out for if you are not feeling well contribute to NDI's encouraging prognosis.