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Madisons Foundation - Moms And Dads In Search Of Needed Support
Nephrogenic Diabetes Insipidus
Tuesday, 16 November 2004
Last Updated Tuesday, 16 November 2004
What
Nephrogenic diabetes insipidus (NDI) is a very rare disorder characterized by the inability of the kidneys to concentrate urine and conserve body water. Diabetes refers to “excessive urination” in Greek and insipidus means “tasteless” in Latin. Unlike in diabetes mellitus (DM), where the urine is sweet, in diabetes insipidus (DI) the urine is neither sweet nor salty. NDI was first described in 1761. Normally, the kidney conserves body water by reabsorbing it from the urinary filtrate. When a person drinks lots of water, the kidneys reabsorb less water and the urine is plenty and dilute. During dehydration, however, the kidneys reabsorb as much water as possible and the urine is minimal and very concentrated. This balance is controlled by a hormone made in the brain called antidiuretic hormone (ADH), which binds to proteins in the kidney and promotes the transport of water molecules from the urine into the blood. There are two types of DI. In central DI (CDI), the brain does not make enough ADH. In NDI, the ADH is unable to exert its effect in the kidney.Who
NDI is estimated to occur in 1 in 200,000 children per year. Children of all races and ethnicities are affected equally. In X-linked NDI, usually only boys are affected. In the autosomally inherited forms of NDI, boys and girls are affected equally. Children with inherited forms of NDI usually present in infancy. Non-inherited (acquired) NDI can present at any age.Signs and Symptoms
Children with NDI urinate more frequently and more profusely, regardless of how much they drink. As a result, they are constantly thirsty and need to drink large amounts of water. They may wet their beds at night because they forget to wake up to urinate. If they cannot keep up with their urinary losses through drinking, then dehydration will occur. Babies with dehydration may have irritability, vomiting, fever, constipation, and poor appetite. Even during dehydration, they will continue to have many wet diapers. As water is depleted from the body, the blood sodium level will rise. In severe dehydration, the blood pressure will drop. This is very dangerous because shock, seizure, and even death can occur. Dehydration can be precipitated by hot weather when more water is lost through sweating and during vomiting or diarrhea. Babies with NDI may not grow well because they must drink large amount of water and do not eat enough. They often have short stature as adults. Dilation of the bladder and the urinary draining system is a complication of high urine volume and predisposes the child to urinary tract infections.Possible Causes
NDI can be inherited or acquired later in life. Ninety percent of inherited NDI is X-linked; 9% is autosomally recessive, and the remaining 1% is autosomally dominant. X-linked NDI is caused by a mutation of the AVPR2 gene. This gene normally makes the ADH-binding protein in the kidney. Autosomally inherited NDIs are caused by a mutation of the AQP2 gene located on chromosome 12. This gene is responsible for making the water-transport protein in the kidney. X-linked NDI usually only affects boys because girls can only be affected if both X chromosomes are mutated. When women are carriers of the mutated gene, 50% of their sons will have NDI. All of the daughters of an affected male will be carriers of one mutated gene, but none of the sons will be affected. A family history of NDI is present in 50% of X-linked NDI cases. In autosomally recessive NDI, two copies of the mutated gene are necessary. Both parents of an affected child must be carriers of the mutant gene. Fifty percent of the children of carrier parents will be carriers; 25% will have NDI, and the remaining 25% will be normal. In autosomally dominant NDI, there is a 50% chance of transmitting the disease to each child. A family history of NDI is usually present. However, as with all the other types of NDI, new spontaneous mutations may occur. Acquired NDI is more common than inherited NDI. It can be caused by medications such as lithium, colchicines, amphotericin B, and gentamicin. Kidney infection, chronic kidney failure, sickle cell disease, and blockage of urine flow to the bladder can also cause NDI.Diagnosis
Urine analysis will reveal dilute urine even during dehydration. The best way to diagnose NDI is through the water deprivation test. This test compares the urine concentrations and blood sodium levels before and after several hours of fasting. In normal situations, the urine should get increasingly concentrated and the blood sodium level remains normal over time. In NDI the urine concentration remains dilute with excessive amounts while the blood sodium level rises. A synthetic form of ADH called DDAVP is administered (often by nasal spray) at the end of the test. In CDI, the kidneys will respond to the DDAVP by producing a smaller volume of more concentrated urine. However, in NDI the kidney cannot respond to the DDAVP and no change in the urine is seen. An MRI of the brain will often be performed to exclude abnormalities of the gland which releases ADH in order to rule out CDI. Genetic testing and prenatal testing for the inherited forms of NDI are available. Renal ultrasound is recommended at diagnosis and every subsequent year to monitor for kidney damage due to NDI.Treatment
There is no cure for NDI. However, research in genetic therapy hopes to one day correct the genetic defect. A kidney specialist (nephrologist) will often be involved in the care of the child. Children with NDI must drink a lot of water to keep up with their urinary losses. Constant access to water and bathrooms is crucial. This is especially important during episodes of vomiting, diarrhea, or excessive sweating. Heat exposure must be minimized. Waking the child at night to urinate may be necessary to prevent accidents. A low sodium diet to help prevent high blood sodium levels is recommended. Breast milk works well in babies. A high protein diet is recommended as well to enable normal growth. Medications can decrease urine volume by 50%. Thiazide diuretics, amiloride and indomethacin are most commonly used to treat NDI. Thiazide diuretics work to increase water reabsorption in the kidneys, thereby concentrating the urine. Because thiazides cause the spilling of potassium into the urine, amiloride is added to the treatment. Indomethacin is an ibuprofen-like medication which can be used with thiazides to decrease urine volume. However, it can cause long-term complications such as stomach ulcers and kidney damage. In cases of severe dehydration, prompt medical attention in necessary. Intravenous fluid replacement may be necessary if the child cannot drink. Care must be taken to decrease the blood sodium to prevent seizures. This is done gradually so as not to cause seizures, coma, brain damage or death. Kidney failure can occur. Also, in severe dehydration, increased blood thickness or viscosity can cause blood to clot.Prognosis
Dehydration and its complications can cause death or long-term problems in children with NDI. Mental retardation can occur due to seizures and recurrent episodes of severe dehydration with decreased blood supply to the brain. In less severe cases, there is risk for attention deficit disorders, hyperactivity and learning disorders. However, if the diagnosis is made early and proper medical care is started, children with NDI can have normal intelligence and life span.Connect with other parents
In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.Weblinks
Nephrogenic Diabetes Insipidus Foundation
Offers education and networking for families.
The Diabetes Insipidus and Related Disorders Network (DIARD)
Provides networking opportunities.
Diabetes Insipidus Foundation, Inc.
Provides information and newsletter