In nephrogenic diabetes insipidus, the kidneys produce a large volume of dilute urine because they fail to respond to antidiuretic hormone and are unable to concentrate urine.

• Often this disorder is hereditary, but it can be caused by drugs or disorders that affect the kidneys.
• Symptoms include excessive thirst and excretion of large amounts of urine.
• Diagnosis is based on tests of blood and urine.
• Drinking large amounts of water, restricting salt in the diet, and sometimes taking drugs reduce urine volume.

Both diabetes insipidus and the better-known type of diabetes, diabetes mellitus, result in the excretion of large volumes of urine. Otherwise, the two types of diabetes are very different.

Two types of diabetes insipidus exist. In nephrogenic diabetes insipidus, the kidneys do not respond to antidiuretic hormone (vasopressin), so they continue to excrete a large amount of dilute urine. In the other, more common, type (central diabetes insipidus), the pituitary gland fails to secrete antidiuretic hormone (see Pituitary Gland Disorders: Central Diabetes Insipidus).

Did You Know... Nephrogenic diabetes insipidus and diabetes mellitus are very different, except that both cause people to excrete large amounts of urine.

Causes

Normally, the kidneys adjust the concentration of urine according to the body's needs. The kidneys make this adjustment in response to the level of antidiuretic hormone in the blood. Antidiuretic hormone, which is secreted by the pituitary gland, signals the kidneys to conserve water and concentrate the urine. In nephrogenic diabetes insipidus, the kidneys fail to respond to the signal.

Nephrogenic diabetes insipidus may be hereditary. The gene that causes the disorder is recessive and carried on the X chromosome, one of the two sex chromosomes, so usually only males develop symptoms. However, females who carry the gene can transmit the disease to their sons. In other people, nephrogenic diabetes insipidus may be caused by certain drugs that block the action of antidiuretic hormone, such as lithiumSome Trade Names
LITHOBID
. Also, high levels of calcium or low levels of potassium in the blood partially block the action of antidiuretic hormone. Nephrogenic diabetes insipidus can also occur if the kidney is affected by disorders such as polycystic kidney disease, sickle cell anemia, medullary sponge kidney, infections (pyelonephritis) that are severe, amyloidosis, Sjögren's syndrome, or myeloma.

Symptoms and Diagnosis

The symptoms of nephrogenic diabetes insipidus are excessive thirst (polydipsia) and the excretion of large volumes of dilute urine (polyuria). When nephrogenic diabetes insipidus is hereditary, symptoms usually start soon after birth. Because infants cannot communicate thirst, they may become very dehydrated. They may develop a fever accompanied by vomiting and seizures.

If hereditary nephrogenic diabetes insipidus is not quickly diagnosed and treated, the brain may be damaged, leaving the infant with permanent mental retardation. Frequent episodes of dehydration can also retard physical development. With treatment, however, an infant who has this disorder is likely to develop normally.

Laboratory tests reveal high sodium levels in the blood and very dilute urine. A doctor may use a water deprivation test to help make the diagnosis (see Pituitary Gland Disorders: Symptoms and Diagnosis).

Prognosis and Treatment

The prognosis is good if nephrogenic diabetes insipidus is diagnosed before the person suffers severe episodes of dehydration. In cases in which the disorder is not inherited, correction of the underlying abnormality usually helps kidney function return to normal.

To prevent dehydration, people with nephrogenic diabetes insipidus must drink adequate amounts of water as soon as they feel thirsty. Infants, young children, and very sick older people must be given water often. People who drink enough water are not likely to become dehydrated, but several hours without water can lead to serious dehydration. A diet low in salt may help. Nonsteroidal anti-inflammatory drugs (NSAIDs) and thiazide diuretics are sometimes used to treat this disorder. NSAIDs and thiazide diuretics act by different mechanisms to increase the amounts of sodium and water that are reabsorbed by the kidney. These changes decrease the volume of urine.

Last full review/revision December 2006 by Peter C. Brazy, MD