Nephrogenic Diabetes Insipidus
(See also Introduction to Disorders of Kidney Tubules.)
In nephrogenic diabetes insipidus, the kidneys produce a large volume of dilute urine because the kidney tubules fail to respond to vasopressin (antidiuretic hormone) and are unable to reabsorb filtered water back into the body.
Often nephrogenic diabetes insipidus 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 of nephrogenic diabetes insipidus is based on tests of blood and urine.
Drinking increased amounts of water helps prevent dehydration.
To treat nephrogenic diabetes insipidus, people restrict salt in their diet and sometimes take drugs to reduce the amount of urine excreted.
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 vasopressin (antidiuretic hormone), so they continue to excrete a large amount of dilute urine.
In central diabetes insipidus, which is more common, the pituitary gland fails to secrete vasopressin.
Normally, the kidneys adjust the concentration and amount of urine according to the body’s needs. The kidneys make this adjustment in response to the level of vasopressin in the blood. Vasopressin, 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
In hereditary nephrogenic diabetes insipidus, the gene that typically 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. Rarely, another abnormal gene can cause nephrogenic insipidus in both males and females.
In the acquired form, nephrogenic diabetes insipidus may be caused by certain drugs that block the action of vasopressin, such as lithium.
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 syndrome, and certain cancers (for example, sarcoma or myeloma).
Also, high levels of calcium or low levels of potassium in the blood, especially if they persist, partially block the action of vasopressin.
Sometimes the cause is unknown.
The symptoms of nephrogenic diabetes insipidus are
People may pass from 1 to 6 gallons (3 to 20 liters) of urine per day.
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.
Older people with dementia are also more likely to develop dehydration because they too may be unable to communicate thirst.
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.
The prognosis is good if nephrogenic diabetes insipidus is diagnosed before the person suffers severe episodes of dehydration.
With treatment, an infant who has this disorder is likely to develop normally. However, if hereditary nephrogenic diabetes insipidus is not quickly diagnosed and treated, the brain may be damaged, leaving the infant with permanent intellectual disability. Frequent episodes of dehydration can also slow physical development.
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 and protein 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.