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).

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.

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.

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.

Published Date: August 13, 2024
Published By: National Institutes of Health