Nephrogenic diabetes insipidus

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 30, 2016
StartDiseasesNephrogenic diabetes insipidus

Nephrogenic diabetes insipidus (NDI) occurs due to kidney problems. The disease may be inherited or acquired. For those with nephrogenic diabetes insipidus, there is an imbalance between fluid intake and output, and large quantities of urine are excreted (polyuria) combined with excessive thirst from dehydration (polydipsia). In severe instances, up to 20 liters a day of urine may be passed. If untreated, this rare disorder can cause serious complications from dehydration. 

Contents

Definition & Facts

Nephrogenic diabetes insipidus (NDI) can be inherited through genetic mutations in which the defective gene is on the X chromosome. Because men have X and Y chromosomes, one mutation can result in the disease. Women have two X chromosomes, so they can inherit the disease only if both X chromosomes are affected. Men are more commonly affected than women.

NDI is more commonly acquired than inherited, and it can be acquired through certain drugs that compromise the minerals in the body or impair kidney function. Certain antibiotics and treatments used for herpes or tuberculosis are possible causes. Lithium, used to treat certain types of mental disordera, is the most common medication to cause NDI. Chronic kidney disease is also a factor.

Symptoms & Complaints

Although some symptoms of NDI are very noticeable such as polyuria, others are less obvious. Sometimes the urethra leading from the bladder dilates with constant pressure, leading to leakage of urine. Because of the large volume of urine excreted, the bladder can become weak and enlarged, and the ureters of the kidney blocked with urine (hydronephrosis).

One of the most disturbing symptoms is excessive nocturnal urination. Bedwetting may occur in children with the disorder, and infants may have frequent episodes of dehydration, leading to weakness and lethargy with unexplained weight loss.

If the episodes continue untreated, children may experience seizures, brain damage, and developmental delays. Some intellectual disabilities may be permanent. Those with NDI in childhood are sometimes shorter than average by the time they reach adulthood due to failure to thrive.

A chronic symptom of adults with NDI is orthostatic hypotension in which blood pressure drops precipitously upon rising from a sitting position or lying down. Syncope, or dizziness and fainting are other symptoms.

Genetic carriers of the disease may exhibit no symptoms. During pregnancy, women may experience some of the increased thirst and increased urinary output characteristic of NDI, but this may remain undiagnosed.

Causes

Most cases of inherited nephrogenic diabetes insipidus are caused by mutations of the AVPR2 gene. About 10 percent of hereditary nephrogenic diabetes insipidus cases are caused by mutations of the AQP2 gene. Mutations of the AVPR2 gene are inherited via X-linked inheritance. Mutations of the AQP2 gene are inherited via either autosomal recessive inheritance or autosomal dominant inheritance.

The chronic symptoms of NDI are caused by the compromised kidney's inability to reabsorb water due to genetic mutations or disease. The filtering tubules in the kidney are unable to respond to a vital hormone called vasopressin (ADH). This is an antidiuretic hormone that triggers the kidneys to concentrate urine.

At rare times, a blockage in the urinary system may cause NDI symptoms. High or low potassium or calcium levels due to acute kidney failure or cardiovascular disease may also cause nephrogenic diabetes insipidus. Brain injury, blockage of blood vessels to the brain, encephalitis, or defects in the hypothalamus or pituitary gland may cause this condition.

Diagnosis & Tests

Restricted water intake, under medical supervision, is a fundamental test for NDI. When fluids are not consumed for a period, the physician can measure changes in body weight, as well as output and concentration of blood and urine. Cautions are taken to make sure that no more than five percent of body weight is dropped, especially for pregnant women.

Lab tests will determine blood levels of ADH, the hormone vasopressin, which concentrates urine. Clinical urine tests will examine the chemical and physical content of urinary output. If the water content of the urine is high in relation to the concentrated substances, NDI may be suspected. 

A renal ultrasound will be performed to check for hydronephrosis, or excessive water stored in the kidney. The bladder will be viewed for changes in size and function. Genetic testing may be offered, due to the inherited nature of some NDI.

Treatment & Therapy

Often, emergency treatment for dehydration must be implemented. The deficit is treated by gradual hydration either via oral hydration or IV fluids. Medications to treat NDI are standard thiazide diuretics and dietary sodium restrictions. Because thiazides cause loss of potassium, they are often combined with another drug like amiloride, which helps retain potassium in those using diuretics.

Nonsteroidal anti-inflammatory drugs, or NSAIDs, have the ability to concentrate urine and reduce its output. Caution is indicated for NSAIDs, because they sometimes have undesirable consequences such as damage to renal tubes and gastric upset. Currently, there is no cure for nephrogenic diabetes insipidus.

Prevention & Prophylaxis

Children who have experienced severe dehydration from undiagnosed nephrogenic diabetes insipidus are at serious risk for delayed development and should be treated and monitored closely. Monitoring includes the charting of growth and annual renal ultrasound to determine any changes.

Relatives may be at risk in families with children suffering from NDI, so genetic testing for the disease may be recommended, especially for siblings of a child with NDI. Genetic testing for those with relatives who are diagnosed may be appropriate before planning a family. Educating neighbors, teachers and family about a child's NDI condition can be very helpful.

Reducing or eliminating medications like lithium salts known to precipitate NDI, can be effective for prophylaxis. Sometimes a swollen bladder may not empty properly, and intermittent catheterization may prevent retention of urine.

All people with NDI are encouraged to eat a low sodium diet. Although a low protein diet was once advised for the disease, the wisdom of this has been questioned, due to nutritional deficiencies that can arise. People with NDI can enjoy a high quality of life, especially if the disease is diagnosed early.