What is Arginine Vasopressin Deficiency (AVP-D)?

AVP Deficiency, formerly known as Diabetes insipidus (DI), is caused by a problem with either the production, or action, of the hormone vasopressin (AVP). If you have AVP-D your kidneys are unable to retain water.

This leads to the production of large volumes of urine and, in turn, greatly increased thirst. AVP Deficiency can occur at any age, but is mostly found in adults. It is a rare disorder, affecting only about 1 in 25,000 people.

Water balance is very important for the body. A large proportion of what we are is made up of water. In addition, the amount of water we have in our circulation is a large factorin determining the balance of salt in our bodies.

As with any function that is important, the body has a sensitive mechanism for regulating water balance. Like any good mechanism it is also simple, involving two key components:

  • Vasopressin (AVP or ADH – antidiuretic hormone) – which regulates the amount of water passed out of the body in urine.
  • Thirst and drinking – which determines the amount of water the body takes in.

AVP (sometimes called Anti-diuretic hormone or ADH) is a hormone released from the rear most part of the pituitary gland (the posterior pituitary). This gland is located at the base of the brain, and is about 3 to 5 centimetres behind the bridge of the nose. AVP circulates in the bloodstream and acts on the kidneys to reduce the amount of water that is passed out in urine.

  • How AVP and thirst work together is best described with the help of the bath tub analogy. As with a bath tub, the body likes to keep the level of water it contains at the right level for its purposes. There are only two ways the level of water can be altered:Water can be let in to the bath through turning the taps on; just as thirst and drinking can allow more water into the body 4 Diabetes insipidus
  • Water can be let out of the bath through taking the plug out; just as the body can let more water out by reducing the amount of AVP produced and so letting more water to be passed out of the body as urine.

Unlike a bath tub, the body is very good at sensing the level of water it has on board. If it does not have enough and is dehydrated, it triggers us to drink more through activating the thirst (turning on the taps). At the same time, it makes more AVP and so reduces water loss in urine (it puts the plug in). On the other hand, if the body senses the level of water is too much, it turns the thirst off (turning taps off) and makes less AVP (taking the plug out of the plug hole). The level of water is therefore maintained through a combined approach.

Together, AVP and thirst maintain water balance very effectively in both situations where water is either easy to find, or is scarce. AVP Deficiency occurs when this mechanism regulating water balance breaks down.

AVP Resistance

AVP Resistance is not a pituitary condition, but it is similar to AVP Defieciency. In this condition the kidneys do not respond to the normal signal (AVP) to reduce water loss. Thus, the kidneys are not able to absorb the water that passes through them.The primary symptoms of AVP Resistance are polyuria (passage of large volumes of urine) and polydipsia (excessive thirst and drinking).

Inherited AVP Resistance may show up in the first weeks of life. Symptoms can include irritability, failure to thrive, lack of appetite and vomiting. Investigation can reveal high blood levels of sodium. Up to 90% of the cases of inherited AVP Resistance are the result of mutations affecting the AVP-receptor (V2R) that is needed for the kidney to respond to AVP and reabsorb water. The remaining cases are the result of mutations in the pore in kidney cells through which water is reabsorbed (AQP2). Though each type of inherited AVP Resistance has a different genetic cause, the symptoms of each are the same.

Males are the most likely to display symptoms of X-linked AVP Resistance, whereas males and females are equally likely to display symptoms of the autosomal recessive form of AVP Resistance. This is because the V2R gene is carried on the X-chromosome and males have only one X-chromosome. A problem with a gene on this single X-chromosome can’t be counter-balanced by another normal X-chromosome (the position in females). Autosomal recessive AVP Resistance is carried on a non-sex chromosome, so males and females are equally likely to inherit the problem.

Acquired AVP Resistance is the more common form of AVP Resistance and can occur at any time of life. Most often, acquired AVP Resistance is a result of the use of the drug lithium. Acquired AVP Resistance can also result from the use of other drugs, such as colchicine, methoxyflurane, amphotericin B, gentamicin, loop diuretics and demeclocycline. It can also occur as a result of certain diseases and physical conditions, which can result in either permanent or temporary AVP Resistance such as:

  • chronic kidney failure
  • other kidney diseases
  • abnormally low levels of potassium
  • abnormally high levels of calcium
  • sickle cell disease 6 Diabetes insipidus
  • And rarely, during pregnancy