Nephrogenic diabetes insipidus Health Article

Definition

Nephrogenic diabetes insipidus (NDI) is a kidney disorder characterized by the organ's inability to respond to the antidiuretic hormone (ADH), also called arginine vasopressin (AVP), produced in the hypothalamus, a structure of the brain. NDI involves an abnormality in the kidney tubules which prevents the proper amount of water from being reabsorbed from the kidneys back into the body. Instead, the water is excreted in large amounts as diluted urine.

Description

There are two categories of nephrogenic diabetes insipidus: inherited and acquired. Within the inherited group, there are three types of NDI: X-linked, autosomal recessive, and autosomal dominant. Unlike the more common diabetic disorder diabetes mellitus, NDI is not related to insulin production or levels of sugar in the blood and urine.

Ninety percent of inherited NDI is X-linked, meaning it is caused by an alteration in a gene carried on the X chromosome. Since women have two X chromosomes and men have only one, an X-linked recessive condition is expected to effect men since they do not have a second X chromosome with a normal copy of the gene to produce the needed substance. Autosomal recessive NDI is rarer and equally affects males and females. Autosomal dominant NDI is the most rare of the three and affects both males and females.

Inherited NDI is present from birth and symptoms usually manifest within the first several days of life. If the disorder is not diagnosed and treated early, it will cause the body to lose too much water. This dehydration can lead to brain damage and eventually death. But, with early diagnosis and treatment to avoid severe dehydration, the person can live a normal life span without any mental impairment.

Acquired NDI is the most common type of the disease and can be acquired at any age. It is most frequently acquired through the long-term use of certain prescription medicine, including demeclocycline, methicillin, foscarnet, and some anticancer drugs. In rare instances, it can be caused by an underlying disease or disorder, such as sickle cell anemia, chronic kidney failure, sarcoidosis, amyloidosis, Fanconi syndrome, and Sjögrens syndrome. Other rare causes of acquired NDI are low blood levels of potassium and abnormally high blood calcium levels. Pregnancy can also result in temporary acquired NDI. However, most cases of acquired NDI are caused by long-term use of the prescription drug lithium, used to treat bipolar disorder (manic depression).

NDI, also called gypsy's curse, is caused by the kidneys inability to respond to the water-saving hormone (ADH), a natural chemical manufactured in the brain but works in the kidneys. The body's two kidneys make urine, which is then sent to the bladder, and help to maintain the balance of water, salt, and minerals. A majority of the water is reabsorbed from nephrons in the kidneys into surrounding inner tissue. Each kidney contains hundreds of thousands of nephrons, microscopic-size tubes that filter the water flowing into the kidneys. The water that is not absorbed becomes urine.

The first references to NDI appeared in medical literature in the 1880s, but it wasn't until the 1940s that detailed observations and studies were done. In a landmark 1946 study published in the American Journal of the Diseases of Children, authors A. J. Waring, L. Kajdi, and V. Tappan, summarized the main clinical and pathophysiological aspects of the disorder. "The presenting complaints were unexplained fever, failure to gain weight, and constipation. The bouts of dehydration are usually not associated with acidosis. The thirst of one of the patients studied was satisfied only when five to six times the normal requirement of fluid was offered. The levels of (blood) serum sodium and chloride decreased to normal and the infant remained free from fever on this high fluid intake."