What is nephrogenic diabetes insipidus?

Nephrogenic diabetes insipidus (NDI) is a rare disease that affects the fluid balance of the kidneys. In NDI, the kidneys dilute the urine excessively because they cannot control urine concentration due to defective hormone function.

NDI is caused by defective vasopressin, also known as antidiuretic hormone (ADH), which is located in two parts of the kidney called the distal tubule and the collecting duct.

NDI occurs when the kidneys do not respond properly to vasopressin and produce too much urine (polyuria), causing a person to be excessively thirsty. As a result, people pass unusually large amounts of diluted and odorless urine.

If left untreated, this massive loss of fluid can lead to severe dehydration, which can lead to 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 lost fluids are not replaced, electrolyte imbalances can result, including symptoms such as:

  • unexplained weakness
  • lethargy
  • Muscle pain
  • irritability

The body’s inability to conserve water also puts you at a higher risk of dehydration. Warning signs of dehydration include:

  • increased thirst
  • dry skin
  • fatigue
  • sluggish
  • Dizziness
  • Puzzled
  • nausea

Excessive water loss in urine may be between 10 and 15 liters per day. Therefore, drinking plenty of water is crucial to staying hydrated.

Types of

The two types of NDI are:

  • Acquired NDI, caused by certain medications and chronic diseases, can occur at any time in life
  • Inherited NDI, the signs and symptoms of which usually appear within the first few months of a baby, as a result of a genetic mutation that affects the kidneys’ ability to hold water
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get NDI

NDI can be obtained in a number of ways, including:

  • Adverse reactions to medications such as lithium or demeclocycline
  • Long-term metabolic imbalance, such as low potassium (hypokalemia) or high calcium in the blood (hypercalcemia)
  • Kidney disease (eg, autosomal dominant polycystic kidney disease, renal amyloidosis)
  • Blockage of the ureters (the tubes that carry urine from the kidneys to the bladder)
  • pregnant. NDI in pregnancy (NDI occurring during pregnancy) occurs for one of two reasons. In some cases, enzymes made by the placenta (the temporary organ that connects mother to baby) break down the mother’s vasopressin. In other cases, pregnant women produce more prostaglandins, hormone-like chemicals that reduce the sensitivity of the kidneys to vasopressin.

hereditary NDI

Most inherited NDI cases are caused by X-linked genetic disorders. X-linked genetic disorders are caused by the inheritance of non-working genes on the X chromosome. Because men have only one X chromosome and women have two, if a man inherits this recessive X-linked nonworking gene from his mother, he is more likely to develop the disease. On the other hand, a woman can be a carrier but cannot acquire this genetic disorder.

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Nephrogenic diabetes insipidus can be caused by inherited genetic changes or mutations that prevent the kidneys from responding to vasopressin, but the vast majority are due to:

  • chronic kidney disease
  • certain medicines, especially lithium
  • low levels of potassium in the blood
  • high calcium levels in the blood
  • Urinary tract obstruction
  • pregnant

The cause of NDI may also be unknown or idiopathic.


The diagnosis of NDI is based on your symptom history and confirmatory tests performed by your doctor or other healthcare provider. The diagnosis of NDI is based on the following:

  • medical and family history
  • physical examination
  • Urinalysis
  • blood test
  • fluid deprivation test
  • Magnetic Resonance Imaging (MRI)


In some cases, NDI may go away after treatment, such as changing medications or taking steps to balance calcium or potassium levels in the body.

Diuretics—sometimes combined with aspirin or ibuprofen—may help control symptoms. Diuretics help the kidneys remove fluid from the body, while aspirin or ibuprofen can reduce the amount of urine. Thiazide diuretics are especially useful because they reduce urine production, allowing the kidneys to concentrate urine more efficiently.


The results of NDI are usually positive. If fluid loss is greater than fluid intake, the main complication is dehydration, but dehydration is usually corrected by drinking more fluids.

Of note, infants and adults with NDI may become dehydrated rapidly following low water intake, exposure to hot conditions, or concurrent illness. Noticing early signs of dehydration in infants is especially important in diagnosing hereditary NDI. Babies may experience repeated dehydration, which can lead to:

  • weakness
  • Puzzled
  • dry mucous membrane
  • dry skin
  • lose weight
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If dehydration is left untreated, serious complications such as seizures, brain damage, developmental delay, and physical and mental disability can occur. However, with proper diagnosis and prompt treatment, intelligence and development are usually normal.

Is there a cure for NDI?

There is no cure for inherited NDI, but with acquired NDI, proper management of the underlying cause of the NDI may lead to relief of symptoms. For example, symptoms caused by your NDI may go away if you stop taking the medicine that caused the NDI.

VigorTip words

If you have mild nephrogenic diabetes insipidus, the only cure is to drink plenty of fluids. Dietary changes (such as reducing salt) and medication (such as using diuretics) may also help reduce urine output.

While there is no cure for genetic forms of NDI, the condition can often be well managed by drinking enough fluids to prevent dehydration. Reaching out to a healthcare professional, noticing your symptoms, and letting family members or friends know if you’re feeling unwell can help with the encouraging prognosis of NDI.