Nephrogenic diabetes insipidus (NDI) is a rare kidney disorder that may be inherited or acquired. NDI is not related to the more common diabetes mellitus (sugar diabetes), in which the body does not produce or properly use insulin. NDI is a distinct disorder caused by complete or partial resistance of the kidneys to arginine vasopressin (AVP). Vasopressin is an antidiuretic hormone used by the kidney to manage water balance in the body. NDI causes chronic excessive thirst (polydipsia), excessive urine production (polyuria), and potentially dehydration. If left untreated, repeated episodes of severe dehydration may develop, eventually resulting in serious complications. Most cases of hereditary NDI are inherited as X-linked recessive disorders. Rare cases are inherited as an autosomal recessive or dominant disorder. Two different genes have been identified that cause hereditary NDI. NDI may also be acquired during life as a result of drug use (e.g., lithium therapy), kidney disease, obstruction of the tubes that carry urine from the kidneys to the bladder (ureters), and prolonged metabolic imbalances such as low levels of potassium in the blood (hypokalemia) or high levels of calcium in the blood (hypercalcemia). NDI may also be a temporary complication associated with pregnancy.

In CDI, symptoms may develop over time or abruptly and may affect individuals of any age. CDI is characterized by excessive thirst (polydipsia) and excessive urination (polyuria), even at night (nocturia). The severity and progression of CDI varies from case to case. Some individuals may have a severe form of the disorder (complete CDI) with little or no vasopressin activity. Others may have a mild form of the disorder (partial CDI) with residual vasopressin activity.

Without appropriate AVP secretion, individuals with central diabetes insipidus are unable to concentrate the urine by reabsorbing water in the kidneys. This results in obligatory excessive urine output of dilute urine. Consequently, individuals must drink excessively to prevent dehydration. In response to thirst, affected individuals may drink several gallons of water a day. If affected individuals are deprived of water for an extended period of time, rapid dehydration will occur. Thirst cravings can be strong enough to awaken people from sleep.

In infants, additional symptoms may occur including irritability, lethargy, vomiting, constipation and fever. If left untreated, repeated episodes of dehydration can potentially result in seizures, brain damage, developmental delays, and physical and mental retardation. However, with proper diagnosis and prompt treatment intelligence and development is usually normal unless more global problems in development of the brain are associated. Affected children may develop bedwetting (enuresis), fatigue, weight loss, and growth retardation.

Individuals with CDI are at risk of developing dehydration and cardiovascular symptoms including irregular heartbeats, fever, dry skin and mucous membranes, confusion, seizures, change in consciousness, and potentially coma. Affected adults may develop orthostatic hypotension, a condition in which there is a dramatic decrease in blood pressure upon standing or sitting. Orthostatic hypotension can result in dizziness or momentary loss of consciousness (syncope).

CDI is caused by partial or complete deficiency of the antidiuretic hormone, arginine vasopressin. This deficiency usually results from damage to the hypothalamus or pituitary gland. In extremely rare cases, vasopressin deficiency is caused by a genetic mutation that is inherited as an autosomal dominant or autosomal recessive trait. In approximately one third of cases, no specific cause can be identified (idiopathic) and may be autoimmune in etiology.

The hypothalamus is a portion of the brain that acts as a link between the brain and the endocrine systems. The hypothalamus releases neuro-hormones that influence the secretion of other hormones such as those that aid in the regulation of various metabolic process, growth, reproductive function and autonomic functions of the body. One of the substances secreted by the hypothalamus is vasopressin, which travels via nerve fibers to the posterior pituitary gland.

The pituitary is a small gland located near the base of the brain that stores several hormones and releases them into the bloodstream as needed by the body. These hormones regulate many bodily functions. The posterior lobe of the pituitary gland is known as the neurophysis (neurohypophsyeal region), which stores hormones and eventually secretes them into the bloodstream. After the hypothalamus produces vasopressin, the hormone travels to the pituitary gland, and is stored in the neurophysis. Vasopressin is eventually released into the bloodstream as needed by the body. Vasopressin travels to the kidneys where it binds to receptor proteins found on the surface of certain kidney cells, initiating a process through which the kidneys reabsorb water into the body. Without proper levels of vasopressin, water is not reabsorbed and is lost through urination.

Damage to the hypothalamus, pituitary gland or the connection between the hypothalamus and pituitary gland (pituitary stalk) may impair the production, transport, storage, or release of vasopressin, which in turn impairs the ability of the body to conserve water. Such damage may occur from trauma due to an accident or surgery (e.g., surgery to remove a tumor in the area), various infections, tumors such as a craniopharyngioma or a germinoma, a rare disease known as Langerhans cell histiocytosis, or a variety of inflammatory, vascular, or granulomatous diseases.

In rare cases, CDI may be inherited as an autosomal dominant trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. Even rarer is an autosomal recessive mode of inheritance in which neither parent is affected but each carries an abnormal gene which when combined together in the offspring result in disease.

Investigators have determined that some cases of inherited CDI are caused by disruptions or changes (mutations) of the arginine vasopressin (AVP) gene. Mutations of the AVP gene impair the production (synthesis) or secretion of vasopressin.

The AVP gene is located on the short arm (p) of chromosome 20 (20p13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Researchers believe that some cases of idiopathic CDI may be caused by autoimmune factors. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons. In CDI, the body produces antibodies or lymphocytes that attack cells that secrete vasopressin.

CDI may also occur as part of a larger syndrome or disorder including Wolfram syndrome or septo-optic dysplasia. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Ensuring proper fluid intake and reducing urine output are essential. Specific treatments include the administration of certain drugs. Specific therapy varies depending upon the severity of vasopressin deficiency. Individuals with the severe form of the disorder may receive replacement therapy with a synthetic form of vasopressin known as desmopressin (DDAVP, 1-desamino-8-D-arginine vasopressin). Desmopressin may be taken orally, injected, or used as a nasal spray.

Individuals with partial CDI and residual vasopressin activity may be treated with other drugs such as hydrochlorothiazide. Infants with diabetes insipidus are particularly problematic and may be treated by diluting the formula with water and with hydrochlorothiazide. DDAVP must be used with caution in this age group since infants have an obligate liquid intake to provide adequate calories for growth.

In cases of hereditary CDI, genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Diabetes associated with the brain and nervous system of the body is Vasopressin-Sensitive Diabetes Insipidus or CDI.

• This rare genetic disorder is diagnosed after the baby is born or in the early years of life.
• Test to measure blood electrolyte levels and sodium levels in the body.
• The body lacks vasopressin for many other reasons like brain damage, brain injury, tuberculosis (TB), and Blockage in arteries reaching the brain.
• Desmopressin is a substitute for vasopressin in the case of CDI which comes in the form of a drug. It is either injected, given as nasal spray, or orally taken as a tablet.
• An imbalance in thirst and urine output leads to dehydration and frequent requirement for lots of water.

Risk Factors of VSDI:

The symptoms of this defect are congenital and it is a hereditary disease. However, if not detected at the time of birth, it is advisable to look for the causes below and not ignore the signs:

• Frequent and prominent dryness in the throat leads to continuous itching and coughing.
• Cracked and inelastic skin with the gradual loss of moisture and sweat.
• Dehydration from an imbalance in electrolyte levels.
• Not feeling hungry and feeling thirsty all the time.
• Forgetfulness, mental disbalances with regular day-to-day work.
• Cramps and stiffness across the muscles of the body.

Symptoms
Weight Loss,Fever,Vomiting,Bed-wetting
Conditions
Excessive Thirst,Excessive Urination,Paleness in Urine,Increased inclination towards Cold Drinks
Drugs
Chlorpropamide,Carbamazepine,Clofibrate,Thiazide Diuretics

Diabetes insipidus occurs due to the deficiency of vasopressin, also known as the antidiuretic hormone (ADH) due to a hypothalamic-pituitary disorder. Hence, it is referred to as the central diabetes insipidus or vasopressin-sensitive diabetes insipidus.
Central diabetes insipidus is of two types:

• Primary central diabetes insipidus: Genetic deformities of the vasopressin gene on Chromosome 20 trigger autosomal dominant forms of the disorder. Most cases are evident to be idiopathic.
• Secondary central diabetes insipidus: Central diabetes insipidus can be acquired (secondary). It can be due to different lesions such as hypophysectomy, intrasellar or suprasellar tumors, cranial injuries, granulomas, lymphocytic hypophysitis, vascular lesions, Langerhans cell histiocytosis, and other infections.

Treatment for vasopressin-sensitive diabetes insipidus:

• Central diabetes insipidus can be treated either by hormonal drugs such as desmopressin or non-hormonal drugs such as diuretics.
• Desmopressin is a synthetic analog of vasopressin. It contains limited vasoconstrictive properties and has long-term antidiuretic action. In most patients, it lasts for more than 12 hours. The drug is usually administered subcutaneously, intranasally, IV, or orally. The duration of action of the drug varies greatly in patients.
• Three groups of non-hormonal drugs are used for decreasing polyuria are Dietetics (Thiazids), Vasopressin-releasing drugs (Carbamazepine, Chlorpropamide) and Prostaglandin inhibitors.
• These non-hormonal drugs are useful in patients having partial central diabetes insipidus.

Symptoms
Weight Loss,Fever,Vomiting,Bed-wetting
Conditions
Excessive Thirst,Excessive Urination,Paleness in Urine,Increased inclination towards Cold Drinks
Drugs
Chlorpropamide,Carbamazepine,Clofibrate,Thiazide Diuretics