Arginine vasopressin resistance

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Arginine vasopressin resistance (previously called nephrogenic diabetes insipidus) is a disorder of water balance. The body normally balances fluid intake by releasing excess fluid in urine. However, people with arginine vasopressin resistance produce an excessive amount of urine (polyuria), which depletes the amount of water in the body. This water loss also leads to excessive thirst (polydipsia).

Affected individuals can quickly become dehydrated if they do not drink enough water. Dehydration can cause dizziness and fatigue. Prolonged dehydration can lead to confusion, low blood pressure, seizures, and coma. People with arginine vasopressin resistance often develop high levels of sodium in the blood (hypernatremia) due to dehydration. Repeated cycles of dehydration can cause long-term health problems, particularly in children.

Arginine vasopressin resistance can be either acquired or familial. The acquired form can occur at any time during life. The familial form usually become apparent within the first year of life, though in some cases they develop in adolescence or early adulthood.

Infants with familial arginine vasopressin resistance tend to have problems feeding and gaining weight (faltering weight). They may also be irritable and experience fevers, diarrhea, and vomiting. Recurrent episodes of dehydration can lead to slow growth and delayed development. If the condition is not well-managed, it can damage the bladder and kidneys leading to pain, infections, and kidney failure. With appropriate treatment, affected individuals usually have few complications and a normal lifespan.

Researchers have recommended using the condition name arginine vasopressin resistance because the previous name, nephrogenic diabetes insipidus, was often confused with a much more common disorder called diabetes mellitus. Arginine vasopressin resistance and diabetes mellitus are separate disorders with different features, causes, and treatment.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

The familial form of arginine vasopressin resistance can be caused by variants (also called mutations) in at least two genes that are active in the kidneys. About 90 percent of all cases of familial arginine vasopressin resistance are caused by variants in the AVPR2 gene. Most of the remaining 10 percent of cases are caused by variants in the AQP2 gene. The AVPR2 gene provides instructions for making the vasopressin V2 receptor protein, and the AQP2 gene provides instructions for of the aquaporin-2 protein. Both of these proteins work with a hormone called arginine vasopressin (AVP) to help determine how much water is released in urine.

Normally, the kidneys filter the blood to remove waste and excess fluid, which are then stored in the bladder as urine. The balance between fluid intake and fluid release is controlled by AVP, which is sometimes also called antidiuretic hormone (ADH). AVP is produced and stored in the brain and it works with the vasopressin V2 receptor and aquaporin-2 proteins in the kidneys to manage fluid balance. Normally, when a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), the brain releases more AVP into the bloodstream. High levels of this hormone direct the kidneys to reabsorb more water and to make less urine. When fluid intake is adequate, the brain releases less AVP.

Variants in the AVPR2 or AQP2 genes lead to the production of proteins that are unable to respond to AVP. The brain produces and releases AVP normally, but the kidneys function as if little or no hormone is present. As a result, the kidneys do not reabsorb water as they should, and the body makes excessive amounts of urine. These problems with water balance are responsible for the dehydration that is characteristic of arginine vasopressin resistance.

The acquired form of arginine vasopressin resistance occurs when the brain is damaged due to head injuries, brain tumors, or other events. It can also be caused by chronic kidney disease, certain medications (such as lithium), low levels of potassium in the blood (hypokalemia), high levels of calcium in the blood (hypercalcemia), or an obstructed urinary tract. The acquired form of arginine vasopressin resistance also causes problems with water balance.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

When arginine vasopressin resisitance is caused by variants in the AVPR2 gene, the condition has an X-linked pattern of inheritance. The AVPR2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a variant in the only copy of the gene in each cell is sufficient to cause the condition. One altered copy of the gene can cause the condition in females (who have two copies of the X chromosome) as well, although the features may be less severe than those seen in individuals with two altered copies, or there may be no signs or symptoms at all. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

When arginine vasopressin resisitance is caused by variants in the AQP2 gene, it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance. In autosomal recessive inheritance, both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. In autosomal dominant inheritance, one altered copy of the AQP2 gene in each cell is sufficient to cause the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of arginine vasopressin resistance is unknown, although the condition is thought to be rare. The acquired form occurs more frequently than the familial form.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Hypernatremia · Very frequent (99-80%)

The concentration of sodium in the blood circulation is above the upper limit of normal.

Hyposthenuria · Very frequent (99-80%)

An abnormally low urinary specific gravity, i.e., reduced concentration of solutes in the urine.

Nephrogenic diabetes insipidus · Obligate (100%)

A form of diabetes insipidus caused by failure of the kidneys to respond to vasopressin (AVP).

Hypernatremic dehydration · Very frequent (99-80%)

Anorexia · Frequent (79-30%)

Lack of desire to eat (loss of appetite).

Constipation · Frequent (79-30%)

Infrequent or difficult evacuation of feces.

Failure to thrive · Frequent (79-30%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Fever · Frequent (79-30%)

Body temperature elevated above the normal range.

Other findings in the same source

From: Orphanet

Additional reported features include Nausea and vomiting (Frequent (79-30%)); Polydipsia (Frequent (79-30%)); Feeding difficulties (Occasional (29-5%)); Functional abnormality of the bladder (Occasional (29-5%)); Growth delay (Occasional (29-5%)); Hydroureter (Occasional (29-5%)); Hypovolemia (Occasional (29-5%)); Renal insufficiency (Occasional (29-5%)); Seizure (Occasional (29-5%)); Short stature (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Arginine vasopressin resistance is Nephrology, with a nephrologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• How is kidney function being assessed over time?
• Are any current medicines or supplements relevant to kidney safety?
• Is there an individual recommendation about fluids, diet or blood pressure?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.