What are the other Names for this Condition? (Also known as/Synonyms)

• Acquired Diabetes Insipidus
• Congenital Diabetes Insipidus

What is Nephrogenic Diabetes Insipidus? (Definition/Background Information)

• The kidneys have two important functions in the body, namely to remove toxic substances from the body and to monitor the amount of water in our body. The structure of kidney can be grossly divided into two parts:
  • Glomeruli: It functions as a strainer, allowing the body to retain the vital nutrients and letting the wastes move ahead for removal or disposal
  • Tubules: It is a system of small tubes that is responsible for the generation of urine. The function of the tubules is to absorb vital nutrients from the fluid that flows through it and maintain a balance of these nutrients in the body. They also help balance the body water state. If the body has too much water, it allows the body to lose water and if dehydration occurs, it helps in absorbing water to maintain a balance          
• The body produces the hormone called antidiuretic hormone (ADH), which helps in regulating body water levels. It makes the kidneys absorb water when there is a state of dehydration in the body
• Diabetes insipidus occurs when there is a defect in the tubules of the kidneys. In this condition, the tubules start to lose excess water irrespective of the hydration status. Thus, the free water is lost, leaving one dehydrated
• In Nephrogenic Diabetes Insipidus, even though the body produces adequate amounts of antidiuretic hormone, the kidneys are unable to respond to this hormone, making it to lose excessive amounts of water. This causes the characteristic signs and symptoms of the condition
• The diagnosis of Nephrogenic Diabetes Insipidus includes a complete medical history and physical examination, checking serum levels of antidiuretic hormone, and water deprivation test
• Complications may occur if the individual is unable to replenish the excessive water loss. These include electrolyte imbalances and shock due to excessive dehydration
• The treatment of Nephrogenic Diabetes Insipidus (acquired form) is aimed at identifying the underlying cause of the condition. The prognosis is good if the condition is detected early and appropriate measurements are taken to prevent complications from occurring
• There are two forms of hereditary Nephrogenic Diabetes Insipidus:
  • Nephrogenic Diabetes Insipidus 1: This type is X-chromosome linked, which means that it affects only the male population, while females are carriers of this condition
  • Nephrogenic Diabetes Insipidus 2: It is very rare and certain other abnormal genes are responsible for this condition            

Who gets Nephrogenic Diabetes Insipidus? (Age and Sex Distribution)

• The congenital form of Nephrogenic Diabetes Insipidus presents soon after birth
• The acquired form the condition can affect both male and female genders, at any age

What are the Risk Factors for Nephrogenic Diabetes Insipidus? (Predisposing Factors)

The risk factors associated with Nephrogenic Diabetes Insipidus include:

• Defective kidney: A chronically damaged kidney is more prone to developing this condition
• Individuals who are on certain medications that can affect the kidneys are more likely at risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Nephrogenic Diabetes Insipidus? (Etiology)

• Inherited Nephrogenic Diabetes Insipidus: It is due to a genetic mutation that causes the antidiuretic hormone receptors in the kidney to function improperly. Thus, the kidneys are not able to respond to ADH stimulation
• Drugs: This is the most common cause in adults with Nephrogenic Diabetes Insipidus. The common drugs that causes the condition include:
  • Lithium: It is used for the treatment of maniac disorders
  • Foscarnet: It is an anti-fungal agent
  • Clozapine: It is used to treat psychiatric diseases
  • Tetracycline: A group of antibiotics used to treat bacterial infections
• Certain electrolyte abnormalities can also lead to this disorder. The common ones include:
  • Hypercalcemia: It refers to high levels of calcium ion in blood. They make the kidney unresponsive to antidiuretic hormone
  • Hypokalemia - low potassium levels in blood

• Certain diseases that damage the kidney tubules can lead to Nephrogenic Diabetes Insipidus. These include:
  • Sickle cell disease: Long-standing sickle cell disease can damage the kidney and may cause this kidney disorder
  • Amyloidosis: Amyloid is a type of protein that if produced in excess can lead to its accumulation in the kidneys, which can progress to development of Nephrogenic Diabetes Insipidus
• Gestational Diabetes Insipidus: It occurs during pregnancy, and is transient, meaning it resolves after pregnancy

What are the Signs and Symptoms of Nephrogenic Diabetes Insipidus?

The signs and symptoms of Nephrogenic Diabetes Insipidus are due to loss of excess water from the body. These develop when the individual is not able to make up the loss of water, which is excreted through urine. The condition can progress to dehydration that presents as:

• Dry mouth
• Loss of skin pressure (turgor pressure)
• Sunken eyes
• In infants, dehydration can also cause sunken fontanelles, which are soft spots on the head

The more advanced form of the condition presents with electrolyte abnormalities with the following signs and symptoms:

• Loss of energy and tiredness
• Mood changes
• Muscle cramps and pain
• Loss of excess water may also lead to decrease in body weight
• Tachycardia: Increased heart rate in response to lowering of blood pressure due to fluid losses

How is Nephrogenic Diabetes Insipidus Diagnosed?

The diagnosis of Nephrogenic Diabetes Insipidus may involve:

• A complete medical history and physical exam findings
• Patients may present with a history of excessive urination and excessive thirst
• The physical exam findings may include:
  • Skin changes
  • Eye changes
  • Decrease in blood pressure
  • High pulse rate

The following tests may be ordered to confirm Nephrogenic Diabetes Insipidus and differentiate it from the other variant, central diabetes insipidus.

• Water deprivation test: It is a confirmatory test to diagnose the condition
  • In this test, the patient is deprived water for a certain period of time and urine is examined at regular intervals for any change in concentration
  • Patients with a normal kidney produces a concentrated urine, whereas, those with diabetes insipidus continues to produce diluted urine signifying an underlying defect          
• Serum levels of antidiuretic hormone: Patients with Nephrogenic Diabetes Insipidus have normal or even elevated levels of this hormone

Some other tests that may be helpful in diagnosing the condition include:

• Urine analysis
• Urine and serum osmolality
• MRI brain scan

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Nephrogenic Diabetes Insipidus?

Complications occur if the individual loses excessive amount of water that is not replenished and also does not seek medical help on time. Most of the complications of Nephrogenic Diabetes Insipidus are due to severe dehydration that leads to:

• Hypernatremia: If the body losses free water, then sodium concentration in blood goes up leading to hypernatremia. This presents as altered mental status and the condition can be life-threatening
• Shock: Very severe form of dehydration may progress to the development of a state of shock. This may result in very low blood pressure and individuals may pass-out due to excessive dehydration

How is Nephrogenic Diabetes Insipidus Treated?

Ensuring that the patient is able to replace the lost fluid is the most important management part to prevent dehydration and development of complications. The treatment of acquired Nephrogenic Diabetes Insipidus is aimed at identifying the underlying cause.

Treatment measures for Nephrogenic Diabetes Insipidus may include:

• Medications to treat the condition:
  • NSAIDs: These are non-steroidal anti-inflammatory medications that act on the kidney and may be helpful in the treatment
  • Thiazide diuretics: These are given with the aim of decreasing the urine output, thus preventing excess water loss from the kidneys          
• Certain dietary measures such as a low salt, low protein diet may be tried
• Discontinuation of the medications that may be responsible for the condition is the first step in the management of drug-induced Nephrogenic Diabetes Insipidus

How can Nephrogenic Diabetes Insipidus be Prevented?

Preventive measures for Nephrogenic Diabetes Insipidus (acquired form) may include:

• Avoiding drugs that are associated with the development of acquired form of the condition
• An appropriate treatment of the underlying disorder is an important step to prevent development of Nephrogenic Diabetes Insipidus

Currently, there are no known preventive measures for the congenital form of Nephrogenic Diabetes Insipidus.

What is the Prognosis of Nephrogenic Diabetes Insipidus? (Outcomes/Resolutions)

The prognosis of Nephrogenic Diabetes Insipidus is good, if the disorder is detected early and appropriate measurements are taken to prevent complications from occuring.

Additional and Relevant Useful Information for Nephrogenic Diabetes Insipidus:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/diabetes/