Nephrogenic diabetes insipidus (AVP resistance): causes and management

The NHS explains that arginine vasopressin (AVP), also called antidiuretic hormone (ADH), is made in the hypothalamus, stored in the pituitary gland and released when the body's water is low, causing the kidneys to make more concentrated urine. In most diabetes insipidus the problem is a lack of AVP. In rare cases the kidneys do not respond to AVP even though there is enough of it, which causes AVP resistance, formerly nephrogenic diabetes insipidus (NDI).

MedlinePlus Genetics explains that the brain produces and releases AVP normally but the kidneys behave as if little or no hormone is present, so they do not reabsorb water as they should and produce excessive urine. People feel thirsty because the body tries to replace the water that is lost. The NHS says diabetes insipidus affects about 1 in 25,000 people in the general population; AVP resistance is the rarer type.

MedlinePlus Genetics notes that researchers recommend the name arginine vasopressin resistance because the previous name was often confused with the much more common diabetes mellitus, which is a separate disorder with different features, causes and treatment.

The NHS lists extreme thirst and passing a lot of urine, even at night, as the two main symptoms, and says that in very severe cases a person can pass up to 20 litres of urine in a day. MedlinePlus Genetics adds that dehydration can cause dizziness and fatigue, and that prolonged dehydration can lead to confusion, low blood pressure, seizures and coma. High sodium in the blood (hypernatraemia) often develops with dehydration.

In familial forms, which usually become apparent within the first year of life, MedlinePlus Genetics says infants tend to have problems feeding and gaining weight, and may be irritable and have fevers, diarrhoea and vomiting. Recurrent dehydration can lead to slow growth and delayed development.

• Extreme thirst.

• Passing very large amounts of dilute urine, including at night.

• Dizziness, fatigue and dehydration if fluids are not replaced.

• In infants: poor feeding, faltering weight gain, irritability, fevers, vomiting.

The NHS says you should always see your GP if you are feeling thirsty all the time. Although it may not be diabetes insipidus, it should be investigated. It also advises seeing a GP if you are peeing more than normal, noting that most healthy adults pass urine 4 to 7 times in 24 hours, or if your child pees more than 10 times a day.

Someone who is known to have AVP resistance and becomes confused, very drowsy, has a seizure or cannot keep fluids down needs emergency care via 999 or A&E, because dehydration with high sodium can be dangerous. An infant who feeds poorly, vomits and seems unusually sleepy or irritable should be assessed urgently.

MedlinePlus Genetics says that the familial form can be caused by variants in at least two genes active in the kidneys: about 90% of familial cases involve AVPR2, which makes the vasopressin V2 receptor protein, and most of the remainder involve AQP2, which makes aquaporin-2. AVPR2 variants cause an X-linked pattern of inheritance, in which males are typically affected, while AQP2 variants can be autosomal recessive or, less commonly, autosomal dominant.

The acquired form, which occurs more frequently, can result from chronic kidney disease, certain medicines such as lithium, low potassium, high calcium or an obstructed urinary tract, according to MedlinePlus Genetics. The NHS also names kidney damage and lithium, used to stabilise mood in some people with conditions such as bipolar disorder, as causes. If you take lithium and are passing much more urine than usual, speak to your prescriber; do not stop it on your own.

The NHS says your GP can carry out a number of tests to help determine what is causing the problem. The pages read for this guide do not detail the tests, so in general terms doctors measure how much urine is passed, check blood and urine concentration (sodium and osmolality), look at kidney function and calcium and potassium levels, and may use a carefully supervised water deprivation test or desmopressin challenge in a specialist centre to distinguish a lack of AVP from kidney resistance to it. Genetic testing can identify AVPR2 or AQP2 variants in suspected familial cases.

The NHS says AVP resistance is often treated with thiazide diuretics, which reduce the amount of urine the kidneys produce, and that rehydration with water treats mild dehydration, while severe dehydration needs treatment in hospital. Where the cause is a medicine such as lithium, a specialist may review the treatment. Treating an underlying cause such as high calcium or low potassium can also improve the condition in acquired cases.

MedlinePlus Genetics says that if the condition is not well managed it can damage the bladder and kidneys, leading to pain, infections and kidney failure, but that with appropriate treatment affected individuals usually have few complications and a normal lifespan. Good access to drinking water, awareness during illness, heat or travel, and regular specialist review are therefore central.

Care in the UK is usually shared between endocrinology and nephrology, with paediatric services for children. The NHS notes that desmopressin is used to replace AVP in the AVP-deficiency type, but it works by replacing the hormone, so it is not the treatment for AVP resistance.