Nephrogenic diabetes insipidus (NDI) is a rare disorder that is caused by large amounts of dilute urine produced by the nephrons, which are found in the kidneys. Normally, the kidneys control the concentration of the urine by absorbing water and returning it to the blood in response to the body's need for water. In a healthy person, an antidiuretic (urine-limiting) hormone called arginine vasopressin (AVP) sends a signal to the kidneys to control the concentration of urine. In patients with NDI, the kidneys are unable to respond to AVP, which causes a problem with water retention. A substantial amount of water that is needed by the body is lost in large quantities as dilute urine. This leaves NDI patients continuously thirsty and in danger of dehydration.
NDI may be either acquired or inherited. Acquired NDI is more common and is usually caused by certain drugs, severe dehydration, or an electrolyte imbalance, such as elevated sodium or chlorine levels in the blood. Inherited NDI is caused by defects in the AVPR2 or AQP2 genes. NDI can be inherited in an X-linked or an autosomal fashion. X-linked mutations are carried on the X chromosome, which is one of the two sex chromosomes. Females have two X chromosomes, whereas males have one X and one Y chromosome. Males are most likely to have symptoms of inherited X-linked NDI because they receive only one X chromosome, compared to females who inherit two X chromosomes. Autosomal mutations are located on one of the 22 non-sex chromosomes. Males and females are equally likely to display symptoms of the autosomal forms of inherited NDI because this form of the disorder is not linked to a sex chromosome.
Symptoms of NDI include extreme thirst (polydipsia), excessive urination (polyuria), short stature, and a failure to develop during infancy. NDI patients require a steady supply of water to alleviate their thirst and to prevent dehydration. With early diagnosis and proper management, the quality and duration of life can be normal for patients with NDI.
NDI is different from diabetes mellitus, which involves problems with insulin and blood sugar regulation. The symptoms can be similar and may include extreme thirst and frequent urination. However, NDI is related to how the kidneys handle fluids. Urine and blood tests can determine if a patient has NDI or diabetes mellitus.
Acquired nephrogenic diabetes insipidus, ADH-resistant diabetes insipidus, arginine vasopressin, AVP, diabetes insipidus renalis, hyperchloremia, hypernatremia, NDI, polydipsia, polyuria, vasopressin-resistant diabetes insipidus.
types of the disease
Acquired NDI: Acquired nephrogenic diabetes insipidus (NDI) occurs more frequently than inherited NDI but is still a rare disorder. It is usually less severe than inherited NDI and can occur at any time during the life cycle. Acquired NDI is usually caused by certain drugs, such as lithium and certain antibiotic, antifungal, chemotherapy, and antiviral drugs. It can also be caused by severe dehydration, urinary blockage, or an electrolyte imbalance, such as an elevated blood sodium level (hypernatremia) or an elevated blood chlorine level (hyperchloremia). When NDI is induced by a drug, the kidneys become damaged in such a way that they are unable to respond to anti-diuretic hormone. Disturbance of the aquaporin-2 shuttle, a channel that makes the kidneys collect more water, is the cause of acquired NDI.
Acquired NDI can also occur as a consequence of more fundamental disorders, such as kidney disease, abnormally low levels of potassium, abnormally high levels of calcium, or sickle cell disease. Acquired NDI may also be caused by one or more of the ureters becoming blocked during pregnancy or as a result of protein starvation. Acquired NDI can be either permanent or temporary, depending on the length of exposure to the drug or condition that caused the symptoms to occur.
Inherited NDI: Inherited NDI is caused by defects in either the AVP receptor 2 gene (AVPR2) or theaquaporin-2 gene (AQP2). Approximately 90% of patients with inherited NDI are males with X-linked recessive NDI who have mutations in the AVPR2 gene, which provides instructions for making the AVP V2 receptor in the kidney. Other modes of inheritance are autosomal recessive (9%) or autosomal dominant (1%), in which the defective gene is AQP2, which provides instructions for making the vasopressin-sensitive water channel in the kidney. Males are more likely than females to be affected by X-linked NDI, whereas males and females are equally likely to display symptoms of the autosomal forms of inherited NDI.
Other: Some doctors have described a third type of NDI called partial NDI. Individuals with partial NDI are diagnosed later in childhood. These individuals usually do not have delayed growth or development, and they are able to concentrate the urine in response to dehydration but not as well as unaffected individuals.