What Is Nephrogenic Diabetes Insipidus (NDI / AVP-R)?

Nephrogenic Diabetes Insipidus (NDI), also increasingly referred to as Arginine Vasopressin Resistance (AVP-R), is a rare kidney disorder in which the kidneys cannot properly respond to arginine vasopressin (AVP), the hormone that helps the body conserve water.

Because the kidneys do not respond normally to AVP, the body cannot properly concentrate urine. Instead, large amounts of dilute urine are produced. This can lead to excessive thirst, frequent urination, dehydration, and elevated sodium levels if fluids are not maintained.

People living with NDI require consistent access to water to replace the fluids lost through urination and to help prevent dehydration.

NDI may be either:

inherited/congenital
acquired later in life due to medications or other medical conditions

A more technical definition comes from Nine Knoers of the University Hospital of Nijmegen in The Netherlands, who described hereditary NDI as a rare inherited kidney disorder marked by insensitivity of the distal renal nephron to the antidiuretic effect of vasopressin.

As a result, the kidney loses its concentrating ability and produces large volumes of hypotonic urine, which can lead to severe dehydration and electrolyte imbalance, including hypernatremia and hyperchloremia.

In simpler terms: the body may have the hormone signal, but the kidneys cannot properly answer it.

Why NDI Is Also Called AVP-R

Full Document

Medical terminology for diabetes insipidus is changing. Nephrogenic Diabetes Insipidus (NDI) is increasingly referred to as Arginine Vasopressin Resistance (AVP-R).

The newer term more clearly describes what happens in the body. In NDI / AVP-R, the body produces arginine vasopressin (AVP), the hormone that helps the kidneys conserve water, but the kidneys cannot properly respond to it. As a result, the kidneys produce large amounts of dilute urine, which can lead to excessive thirst, dehydration, and elevated sodium levels if fluids are not maintained.

This terminology also helps reduce confusion with diabetes mellitus, which is a different condition involving blood sugar and insulin. Families have often reported confusion in schools, hospitals, and emergency settings when the word “diabetes” is misunderstood.

You may see several terms used for the same condition:

Nephrogenic Diabetes Insipidus
NDI
Arginine Vasopressin Resistance
AVP-R

For now, NDI is still widely used by families, clinicians, hospitals, medical records, and online resources. For that reason, NDIF uses both terms together: NDI / AVP-R.

The related condition formerly called central diabetes insipidus is now increasingly referred to as Arginine Vasopressin Deficiency (AVP-D). In AVP-D, the body does not produce enough vasopressin. In AVP-R, the kidneys are resistant to vasopressin.

Read the full explainer: Why NDI Is Now Also Called AVP-R.

How NDI Affects the Body

Under normal circumstances, arginine vasopressin (AVP) signals the kidneys to conserve water when the body needs it.

In NDI / AVP-R, the kidneys are unable to properly respond to that signal. As a result:

too much water leaves the body through urine
urine becomes extremely dilute
the body struggles to retain enough water

This can lead to:

excessive urination (polyuria)
excessive thirst (polydipsia)
dehydration
elevated sodium levels (hypernatremia)
fatigue and irritability
difficulty maintaining hydration during illness or heat

Infants and young children with NDI may be especially vulnerable to dehydration because they cannot always communicate thirst effectively.

NDI vs AVP-D

NDI / AVP-R is different from another condition called AVP-D (Arginine Vasopressin Deficiency), formerly known as central diabetes insipidus.

Although both conditions can cause excessive thirst and urination, they have different underlying causes.

NDI / AVP-R

The body produces vasopressin
The kidneys cannot properly respond to it

AVP-D

The body does not produce enough vasopressin

Because these conditions can appear similar, proper medical evaluation is important to determine the correct diagnosis and treatment approach.

Comparison chart explaining the difference between AVP-R and AVP-D, including cause, hormone levels, affected body system, symptoms, and treatment approach.

Types of NDI

NDI / AVP-R may be either inherited or acquired. Inherited NDI is usually present from birth or early infancy, while acquired NDI develops later in life because of a medication, medical condition, or underlying disorder.

Acquired NDI

Acquired NDI can develop at any time. It may occur:

through the use of certain prescription medications
as a result of kidney disease or another physical condition
because of an underlying systemic disease or disorder

Acquired NDI occurs more often than inherited NDI, but it is still considered rare. It is usually less severe than inherited NDI and more often appears in adults, since it is typically related to a treatment or medical condition that develops later in life.

Lithium therapy is one of the most common causes of acquired NDI.

Inherited (Congenital) NDI / AVP-R

Inherited NDI is rare. Symptoms may appear in the first days or weeks of life, especially in more severe forms.

There are three main inherited patterns:

1. X-linked NDI

X-linked NDI is the most common inherited form. About 90% of hereditary NDI cases are X-linked. This form is usually caused by changes in the AVPR2 gene and affects males more often and more severely than females.

Males who inherit the affected gene are typically seriously affected. Females who carry the gene may have mild symptoms, no symptoms, or, rarely, symptoms as severe as males. A female carrier has a 50% chance of passing the affected gene to each child.

2. Autosomal recessive NDI

Autosomal recessive NDI is much rarer. It affects males and females equally. This form is usually associated with changes in the AQP2 gene.

For a child to have autosomal recessive NDI, both parents usually carry one copy of the affected gene. When both parents are carriers, each pregnancy has a 25% chance of producing a child affected by NDI.

3. Autosomal dominant NDI

Autosomal dominant NDI is extremely rare. It can affect males and females. In this form, only one parent needs to carry the affected gene for there to be a chance of passing it on to a child.

Infographic explaining three inherited patterns of AVP-R, formerly called NDI: X-linked, autosomal recessive, and autosomal dominant inheritance.

Occurrence

Inherited NDI is very rare. The X-linked form accounts for about 90% of hereditary cases, while autosomal recessive and autosomal dominant forms are much less common. GeneReviews estimates hereditary NDI inheritance patterns at approximately 90% X-linked, 9% autosomal recessive, and 1% autosomal dominant.

Daniel G. Bichet has reported that about 90% of congenital NDI patients are males with X-linked NDI caused by mutations in the AVPR2 gene.

Common Symptoms of NDI

Symptoms can vary depending on age and severity but often include:

excessive thirst
excessive urination
waking frequently during the night to urinate
preference for cold water
dehydration
elevated sodium levels
irritability in infants and children
poor weight gain or feeding difficulties in infants
fatigue
constipation
dry skin or dry mouth

Symptoms may worsen during:

illness
hot weather
limited access to water
vomiting or diarrhea

Important Note

This information is intended for educational purposes only and should not replace individualized medical care or professional medical advice. If you suspect dehydration or are concerned about symptoms related to NDI / AVP-R, contact a qualified healthcare provider immediately.

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