Nephrogenic Diabetes Insipidus

Nephrogenic Diabetes Insipidus: What Is It?

When the kidneys cannot concentrate urine, it is known as nephrogenic diabetes insipidus (NDI). This is very rare and affects how the body is able to balance the intake of fluids to help with excreting urine. Those with NDI will produce too much urine, known as polyuria, and find that they are thirsty all the time, known as polydipsia.

The balance in the body is regulated by the hormone vasopressin; the antidiuretic hormone (ADH). The kidney helps to filter all the excess water and waste from the blood and stores the liquid in the bladder. The kidneys will make less urine when indicated by the ADH when the level of intake of fluid is low. When the intake of fluid is high, the hormone tells the kidneys that more urine is needed.

This is a disorder that is both genetic and non-genetic. It can happen due to certain medications or a chronic disease or due to mutated genes passed through families. The mutations and conditions affect the way that ADH functions.

The NDI symptoms make it difficult to diagnose it early in life. Doctors need to use blood and urine tests for this. It is possible to treat it through the use of medications.

Nephrogenic Diabetes Insipidus Causes

NDI causes are both genetic and acquired. It can be passed on through families through a genetic mutation or it can happen due to some sort of drug use or a disease. When it is genetic, it is due to either one of two different genes being mutated: AQP2 or AVPR2. These mutations are either due to damage or mistakes. 90% of the mutation reasons are because of the AVPR2 gene, according to the National Library of Medicine.

The AVPR2 mutations are classified as being X-linked recessive disorders. They are an x-chromosome defect. As males only have one of these chromosomes, they will have the disease if they inherit this mutation. Women will need to have both of their x-chromosomes for the disease to be inherited.

The other 10% of gene mutation causes of NDI are linked to the AQP2 gene, which is autosomal recessive predominately. The only way to suffer from it this way is for the person to have inherited it through both parents. It is possible that it is autosomal dominant, where only one copy of the gene is inherited, but this is extremely rare.

When the NDI is acquired, it is usually due to drug use. However, there are some medical conditions and diseases that lead to the organs becoming damaged due to affected minerals in the body.

The drugs linked to NDI are:

  • Lithium used over the long term for mental problems like bipolar disorder
  • The antibiotic demeclocycline
  • Rifampin for tuberculosis
  • The antibiotic methicillin
  • Foscarnet for herpes

The most common medical conditions that are linked to NDI are:

  • Polycystic kidney disease ureteral obstruction, where cysts on the kidneys block the urinary tract
  • Hypokalemia, where the blood is low in potassium
  • Hypercalcemia, where the blood has too much calcium
  • Primary renal disease

Nephrogenic Diabetes Insipidus Symptoms

Symptoms of the disease as a patient grows up and the most severely affected are infants. However, the symptoms can look like other disorders and it isn’t until childhood that they become more recognizable. It is important to make a diagnoses otherwise the disease can cause death.

Infant symptoms of NDI include:

  • Vomiting
  • Constipation
  • Recurring fevers without a reason
  • Too many wet diapers

Symptoms in young children include:

  • Toilet training difficulties
  • Bedwetting
  • Mental confusion due to dehydration
  • Failure to thrive

Symptoms in older children include:

  • Disturbed sleep
  • Fatigue due to night urination
  • Failure to thrive
  • High urine output
  • Anorexia – low weight due to more water intake than food

Symptoms in adults include:

  • Excessive thirst
  • More urination than normal
  • The blood has a higher level of sodium
  • Frequent trips to the toilet in the night

Rare symptoms that can be fatal include:

  • Hypovolemic shock, where there isn’t enough blood to pump due to dehydration
  • Hypernatremic seizure, where high sodium levels in the blood cause seizures

Diagnosing Nephorgenic Diabetes Insipidus

To prevent the life-threatening complications, an early diagnosis is essential. There are a number of tests to check for the low fasting urine osmolality when there is severe water depletion. These tests include:

  • A polyuria test over 24 hours to measure the urine output
  • First morning test to measure the urine’s gravity from the first one of the morning. This tests the molecules and chemicals in the urine
  • Measuring the sodium potassium, density, pH, chloride and other factors of the urine

Other tests that are carried out include:

  • Renal sonography to make sure there are no renal disorders and to check for any long term damage
  • MRI etiology
  • Water deprivation test. This can be fatal and is only carried out under certain medical teams who are fully knowledgeable. The patient will not drink water to see how the urine release is changed
  • Blood tests to check for the levels of creatine, chloride, urea, sodium potassium and many others

Treating Nephrogenic Diabetes Insipidus

The treatment is about regulating the body’s mechanism of thirst and the amount of released urine. Medications are used to this, including:

  • Bendroflumethiazide to reduce thirst and frequency of nighttime urination
  • Desmopression for treating the genetic NDI
  • Amiloride, indomethacin, thiazide and other drugs for regulating the excretion of water

Other treatments are:

  • Low sodium diet
  • 5% glucose replenished intravenously
  • Intravenous hydration for severe dehydration

The Future for Patients with Nephrogenic Diabetes Insipidus

Children with NDI that is untreated will fail to thrive. They can also suffer from mental retardation because of the constant dehydration in the body when the cases are severe.

When NDI is not treated, there can be dehydration complications that can lead to death. Those who keep their health stable and receive treatment have a good prognosis.