OVERVIEW

What is nephrogenic diabetes insipidus?

The hypothalamus in the brain synthesizes a substance called antidiuretic hormone (ADH). Under normal circumstances, ADH is released into the bloodstream as needed and acts on the kidneys to concentrate urine, maintaining normal urine output.

Nephrogenic diabetes insipidus is a disorder caused by partial or complete insensitivity of the kidneys to antidiuretic hormone, leading to impaired urine concentration.

Who is commonly affected by nephrogenic diabetes insipidus?

Nephrogenic diabetes insipidus can occur at any age.

What are the types of nephrogenic diabetes insipidus?

It is mainly divided into congenital and acquired types.

• Congenital nephrogenic diabetes insipidus is caused by genetic mutations or may occur secondary to certain inherited disorders, primarily affecting children.

• Acquired nephrogenic diabetes insipidus is more common than the congenital form and can result from medications, electrolyte imbalances, or obstructive kidney diseases, such as chronic lithium use or hypercalcemia.

SYMPTOMS

What are the common manifestations of nephrogenic diabetes insipidus?

• Patients may exhibit typical symptoms of polydipsia, polyuria, and nocturia. Specifically, they may experience frequent thirst, excessive water intake, and increased urination frequency, with a 24-hour urine output ranging from 5 to 10 liters or even more. This can disrupt daily activities and sleep, leading to a decline in quality of life.

• Excessive urination can cause dehydration, resulting in symptoms such as lethargy, hypotension, and dry skin. Electrolyte imbalances in the blood are also common.

• Infants with congenital nephrogenic diabetes insipidus may develop recurrent high fever, vomiting, growth restrictions, brain damage, and intellectual disabilities shortly after birth.

Can nephrogenic diabetes insipidus lead to serious consequences?

If left untreated and uncontrolled over the long term, nephrogenic diabetes insipidus can lead to neurogenic bladder, dilation of the urinary tract and renal pelvis, and renal cortical atrophy. Patients may face the risk of kidney failure at a young age. Some patients may also develop venous thrombosis, shock, or even death.

CAUSES

What are the common causes of nephrogenic diabetes insipidus?

• As mentioned earlier, congenital nephrogenic diabetes insipidus is caused by gene mutations or inherited disorders, such as Bardet-Biedl syndrome, cystinosis, etc.

• Causes of acquired nephrogenic diabetes insipidus include:

  • Medications: Besides lithium, nephrogenic diabetes insipidus can be induced by various drugs. These include cidofovir and foscarnet (used to treat cytomegalovirus infections in HIV patients), vasopressin V2 receptor antagonists (which induce transient nephrogenic diabetes insipidus and can treat hyponatremia), amphotericin B, demeclocycline, ifosfamide, ofloxacin, orlistat, and didanosine. Drug-induced nephrogenic diabetes insipidus is usually reversible, at least partially.

  • Electrolyte imbalances: Hypercalcemia, hypokalemia, etc.

  • Kidney diseases: Symptomatic nephrogenic diabetes insipidus can also occur in various kidney disorders, including after relief of bilateral urinary tract obstruction, sickle cell disease or trait, autosomal dominant polycystic kidney disease and medullary cystic kidney disease, renal amyloidosis, and Sjögren's syndrome.

DIAGNOSIS

What tests are needed to diagnose nephrogenic diabetes insipidus?

Water deprivation test, vasopressin test, blood electrolytes, blood glucose, blood osmolality, urine osmolality, urine specific gravity, pituitary MRI. Genetic testing may be performed if necessary.

Why are these tests performed for nephrogenic diabetes insipidus? What is their purpose?

• Water deprivation test: Confirms the presence of diabetes insipidus. The patient abstains from water for 6–16 hours. Normally, urine output decreases significantly, and urine specific gravity and osmolality rise sharply. In diabetes insipidus, urine output remains high, with minimal changes in specific gravity and osmolality.

• Vasopressin test: After water deprivation, arginine vasopressin (antidiuretic hormone) is injected. Patients with nephrogenic diabetes insipidus show no change in urine osmolality after injection.

• Blood and urine osmolality, urine specific gravity: Serve as diagnostic indicators for the water deprivation and vasopressin tests.

• Blood electrolytes: Assesses whether excessive urination has caused electrolyte imbalances (e.g., sodium, potassium, calcium) for timely intervention.

• Blood glucose: Elevated blood glucose can also cause excessive thirst and urination, aiding in differentiation from diabetes insipidus.

• Pituitary MRI: Determines whether pituitary disorders are causing central diabetes insipidus.

• Genetic testing: Identifies the presence and type of genetic mutations.

What precautions should be taken for the water deprivation test in nephrogenic diabetes insipidus?

• Before the test, water intake should be minimized for 1–2 weeks to avoid affecting results. During the test, blood and urine samples are taken hourly.

• Patients may experience worsening thirst and lethargy during the test, which is normal. Doctors monitor weight, blood pressure, and pulse to decide whether to continue. If necessary, intravenous fluids are administered.

Which diseases are easily confused with nephrogenic diabetes insipidus?

Nephrogenic diabetes insipidus must be differentiated from psychogenic polydipsia, central diabetes insipidus, diabetes mellitus, and chronic kidney disease. Diagnosis is typically confirmed via water deprivation test, vasopressin test, pituitary MRI, and genetic testing.

TREATMENT

Which department should I visit for nephrogenic diabetes insipidus?

Endocrinology or Nephrology.

How is nephrogenic diabetes insipidus treated?

• First, a low-salt, low-protein diet, diuretics, and nonsteroidal anti-inflammatory drugs can reduce urine output in NDI patients. A low-sodium diet is recommended for all infants and young children. For adults, the decision to initiate treatment depends on the individual patient's tolerance to polyuria and polydipsia.

• Ensure adequate water intake and nutritional intake. Patients with severe dehydration due to gastrointestinal fluid loss (vomiting, diarrhea) or fever may require intravenous fluids, typically 5% glucose solution or 1/4 normal (0.22%) saline.

• Thiazide diuretics combined with a low-solute diet can reduce the degree of polyuria in NDI patients. If the effect is insufficient, amiloride may be added to enhance efficacy.

What precautions should be taken when using medication for nephrogenic diabetes insipidus?

After starting medication, avoid excessive water intake to prevent water intoxication.

If unexplained symptoms such as headache, vomiting, oliguria, chest tightness, shortness of breath, weight gain, or seizures occur, or if systemic infection, fever, or diarrhea develops—which may indicate water intoxication—seek medical attention immediately. Follow-up visits should also be scheduled as directed by the doctor.

Is follow-up necessary after treatment for nephrogenic diabetes insipidus? How is it conducted?

Yes, follow-up is required. Doctors will regularly assess symptoms of polydipsia and polyuria, blood electrolytes, blood and urine osmolality, urinary tract ultrasound, and growth and development in pediatric patients.

Can nephrogenic diabetes insipidus be cured?

Current medical technology cannot cure congenital diabetes insipidus; it can only alleviate symptoms. Some cases of acquired diabetes insipidus may be cured after addressing the underlying cause.

DIET & LIFESTYLE

What should patients with nephrogenic diabetes insipidus pay attention to in daily life?

• Infant patients cannot drink water actively, grow rapidly, have immature gastrointestinal development, and have high water content in their diet. Professional doctors should comprehensively consider these factors to provide appropriate nutritional intake and water intake to prevent dehydration and excessive water consumption.

• For child and adolescent patients, a low-salt diet is recommended, along with reasonable protein intake to support growth and development. They should drink water when thirsty and avoid consuming large amounts at once. Additionally, they should develop a habit of urinating regularly and completely emptying the bladder to protect the urinary system.

Can patients with nephrogenic diabetes insipidus have children normally?

Yes. There is currently no evidence that diabetes insipidus affects fertility.

Is nephrogenic diabetes insipidus always hereditary?

Congenital nephrogenic diabetes insipidus has a genetic tendency.

PREVENTION

Can Nephrogenic Diabetes Insipidus Be Prevented?

Currently, there is no specific prevention method for congenital nephrogenic diabetes insipidus. Early detection and treatment are the only options.

Prevention of acquired nephrogenic diabetes insipidus mainly involves avoiding self-administration of aminoglycoside antibiotics, amphotericin B, etc., and actively treating urinary system diseases such as kidney stones and hydronephrosis.