Nephrogenic Diabetes Insipidus (NDI) is a rare disorder that occurs when the kidneys are unable to concentrate urine. In most people, the body balances intake of fluids with urine excretion. However, people with NDI produce excessive amounts of urine (a condition called polyuria), which result in insatiable thirst (called polydipsia). This balance regulated by a hormone called vasopressin or antidiuretic hormone (ADH). Waste and excess water in the blood are filtered through the kidneys, which store liquid waste in the bladder. When fluid intake is low, levels of ADH increase and signals the kidneys to make less urine. Conversely, when fluid intake is high, ADH levels decrease and cause the kidneys to create more urine.
NDI can be acquired (through chronic disease or use of certain medications) or inherited (caused by genetic mutations passed down through families). These conditions and mutations interfere with the normal functioning of ADH.
The symptoms of NDI make diagnosis difficult in childhood. To help with diagnosis, doctors use urinary and blood tests. Most cases of NDI are treated with medications.
The cause of NDI can be acquired or genetic, which means it can be caused by something like another disease or drug use (acquired), or genetic, when you inherit the disorder from your parents. Genetic NDI is caused by a mutation in one of two genes: AVPR2 or AQP2. Mutations are mistakes or damage that causes a change in the genes of a person. According to the National Library of Medicine (NLM), 90 percent of cases of inherited NDI are due to mutations in the AVPR2 gene. (NLM, 2010)
Mutations of AVPR2 gene are classified as X-linked recessive disorders, meaning that the gene defect is on the X chromosome. Because males have only one X chromosome, if they inherit an X chromosome with the gene mutation, they will have the disease. Because women have two X chromosomes, in order for them to have the disease, both X chromosomes will have to have the gene mutation.
A smaller percentage of genetic NDI is caused by mutations in the AQP2 gene, which is primarily autosomal recessive. This means a person must receive a copy of the abnormal gene from each parent in order to develop NDI. In very rare cases, AQP2 is autosomal dominant, meaning that a person only receives one copy of the mutated gene.
NDI can also be acquired. Most acquired forms are from drug use. Medical conditions that affect the minerals of the body or damage the organs can also be from NDI.
Drugs that can cause acquired NID include:
- long-term use of lithium, used to treat bipolar disorder and other mental problems
- demeclocycline, an antibiotic
- rifampin, used to treat tuberculosis
- methicillin, an antibiotic
- foscarnet, used to treat herpes
Medical conditions that can cause acquired NID include:
The symptoms of NDI vary with age. Infants are severely affected, but symptoms resemble many other disorders. As children age, symptoms begin to become more recognizable. If a diagnosis is not made, symptoms can become severe enough to cause death.
Symptoms seen in infants include:
- excessive wet diapers
- recurring fevers of unknown origin
Young children present with symptoms including:
- difficulties in toilet training
- failure to thrive
- mental confusion caused by dehydration
Older children to teenagers display symptoms that include:
- high urine output
- disturbed sleep and easy fatigue from night urination
- anorexia (low weight) from preferring water to food
- failure to thrive
Adults display the most common symptoms, which include:
- excessive thirst
- excessive urination
- frequent urination during the night
- increased sodium in the blood
Rare and fatal symptoms include:
- death due to hypovolemic shock (when severe dehydration results in there not being enough blood for your heart to pump)
- hypernatremic seizure (seizures caused by extreme high levels of sodium in the blood)
Early diagnosis of NDI is important in preventing life-threatening complications. Tests are ultimately looking for low fasting urine osmolality in the presence of severe water depletion.
Types of urine testing include:
- polyuria test– measures 24-hour urine output by direct collection
- first morning test– measures specific gravity of urine from first morning collection that tests all the chemicals and molecules in the urine
- measurement of pH, density, sodium potassium, chloride etc.
Other tests for NID include:
- MRI etiology
- renal sonography– to rule out renal disorders and look for long-term damage
- blood test– to measure sodium potassium, chloride, urea, creatine, etc.
A water deprivation test (WDT) can be potentially life threatening and is done only under knowledgeable medical teams. The test has the patient refrain from drinking water to see if there is any change in the amount of urine released.
Treatment focuses upon regulating the thirst mechanism and amount of urine released. Medication can be used for successful treatment.
Medications for NID include:
- bendroflumethiazide (bendrofluazide)– reduces thirst and night urination frequency
- desmopressin– used to treat genetic NID
- drugs to regulate water excretion (thiazide, amiloride, indomethacin etc.)
Other treatment options for NID include:
- intravenous hydration in cases of severe dehydration
- diet low in sodium
- intravenous replenishment of five percent glucose
Children who go untreated for NDI can fail to thrive. In severe cases, they may experience mental retardation from the body’s constant dehydration.
Without treatment, NDI can lead to death from dehydration complications. Prognosis is good for those who receive treatment, and medications can keep health stable.