|
(see Pituitary Disorders: Central Diabetes Insipidus)
Nephrogenic
diabetes insipidus is an inability to concentrate urine due to impaired
renal tubule response to ADH (vasopressin), which leads to excretion
of large amounts of dilute urine. It can be inherited or occur secondary
to conditions that impair renal concentrating ability. Symptoms
and signs include polyuria and those related to dehydration and
hypernatremia. Diagnosis is based on measurement of urine osmolality
changes after water deprivation and administration of exogenous
ADH. Treatment consists of adequate free water intake, thiazide diuretics,
NSAIDs, and a low-salt, low-protein diet.
Nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate urine in response to ADH. Central diabetes insipidus is characterized by lack of ADH. Either type of diabetes insipidus may be complete or partial.
Etiology
NDI can be
Inherited NDI:
The most common inherited disorder is an X-linked trait that affects the arginine vasopressin (AVP) receptor 2 gene. In rare cases, NDI is caused by an autosomal recessive or autosomal dominant mutation that affects the aquaporin-2 gene. Except with the autosomal dominant form, patients who are homozygous are completely unresponsive to ADH. Patients who are heterozygous have normal or slightly impaired responsiveness to ADH.
Acquired NDI:
Acquired NDI can occur when disorders (some of them heritable) or drugs disrupt the medulla or distal nephrons and impair urine concentrating ability, making the kidneys appear insensitive to ADH. These disorders include the following:
Acquired NDI can also be idiopathic. A mild form of acquired NDI can occur in any patient who is elderly or sick or who has acute or chronic renal insufficiency.
In addition, certain clinical syndromes can resemble NDI:
Symptoms and Signs
Generation of large amounts of dilute urine (3 to 20 L/day) is the hallmark. Patients typically have a good thirst response, and serum Na remains near normal. However, patients who do not have good access to water or who cannot communicate thirst (eg, infants, elderly patients with dementia) typically develop hypernatremia from extreme dehydration; hypernatremia may cause neurologic symptoms, such as neuromuscular excitability, confusion, seizures, or coma.
Infants
with inherited NDI may develop brain damage with permanent intellectual disability
if treatment is not started early. Even with treatment, physical growth is often retarded in affected children presumably because of frequent dehydration.
Diagnosis
NDI is suspected in any patient with polyuria (see also Approach to the Genitourinary Patient: Polyuria). Initial testing includes 24-h urine collection (without fluid restriction) for volume and osmolality, and serum electrolytes.
Patients with NDI excrete > 50 mL/kg of urine/day (polyuria). If urine osmolality is < 300 mOsm/kg (water diuresis), central or nephrogenic diabetes insipidus is likely. With NDI, urine osmolality is typically < 200 mOsm/kg despite clinical signs of hypovolemia (normally, urine osmolality is high in patients with hypovolemia). If osmolality is > 300 mOsm/kg, solute diuresis is likely. Glucosuria and other causes of solute diuresis must be excluded.
Serum Na is mildly elevated (142 to 145 mEq/L) in patients with adequate free water intake but can be dramatically elevated in patients who do not have adequate access to free water.
The diagnosis is confirmed by a water deprivation test (see Pituitary Disorders: Diagnosis), which assesses the maximum urine concentrating ability and response to exogenous ADH. After 3 to 6 h of water deprivation, the maximal osmolality of urine in patients with NDI is abnormally low (< 400 mOsm/kg, usually < 300 mOsm/kg). NDI can be distinguished from central diabetes insipidus (lack of ADH) by administering exogenous ADH (aqueous vasopressin 5 units sc, or desmopressin 10 μg intranasally) and measuring urine osmolality. In patients with central diabetes insipidus (see Pituitary Disorders: Central Diabetes Insipidus), urine osmolality increases 50 to 100% over the 2 h after administration of exogenous ADH (15 to 45% in partial central diabetes insipidus). Patients with NDI usually have only a minimal rise in urine osmolality (< 50 mOsm/kg; up to 45% in partial NDI).
Treatment
Treatment consists of ensuring adequate free water intake; providing a low-salt, low-protein diet; and correcting the cause or stopping any likely nephrotoxin. Serious sequelae are rare if patients can drink at will.
If symptoms persist despite these measures, drugs can be given to lower urine output. Thiazide diuretics ( hydrochlorothiazide , 25 mg po once/day or bid) can paradoxically reduce urine output by diminishing water delivery to ADH-sensitive sites in the collecting tubules. NSAIDs (eg, indomethacin ) or amiloride can also help.
Last full review/revision September 2009 by Peter C. Brazy, MD
Content last modified September 2009
| 
