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(See also 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 (in central diabetes insipidus,
inadequate ADH production leads to the same sequelae). It can be
inherited or secondary to conditions that impair renal concentration.
Symptoms and signs include polyuria and those related to dehydration
and hypernatremia. Diagnosis is based on measurement of urine osmolarity
changes after water deprivation and/or 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) can be inherited, most commonly as an X-linked trait, but in rare cases is recessive. Homozygotes are completely unresponsive to ADH. Heterozygotes have normal or slightly impaired responsiveness to ADH.
Acquired NDI can occur when disorders disrupt the medulla or distal nephrons and impair urine concentrating ability, making the kidneys appear insensitive to ADH. These disorders include medullary and polycystic disease; sickle cell nephropathy; release of obstructing periureteral fibrosis; medullary sponge kidney; pyelonephritis; hypokalemic and hypercalcemic nephropathies; amyloidosis; Sjögren's syndrome; and myeloma. Certain nephrotoxins, especially lithium and demeclocycline , can cause NDI.
A mild form of acquired NDI can occur in any patient who is elderly or sick or who has acute or chronic renal insufficiency. An unusual form of transient ADH resistance also occurs in some women in the latter half of pregnancy (gestational diabetes insipidus).
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 their thirst (eg, infants, elderly patients with dementia) typically develop hypernatremia from extreme dehydration.
Infants
with inherited NDI may develop brain damage with permanent mental
retardation 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 producing a large amount of dilute urine. Glycosuria 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. Urine osmolality is typically < 200 despite clinical signs of hypovolemia.
The diagnosis is confirmed by a water deprivation test, 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 NDI patients is abnormally low (< 400 mOsm/kg). NDI can be distinguished from central diabetes insipidus (lack of ADH) by administering exogenous ADH (5 units of aqueous vasopressin sc or desmopressin 10 μg intranasally). 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, whereas patients with NDI have only minimal rise in urine osmolality (< 50 mOsm/kg).
Treatment
Treatment consists of ensuring adequate free water intake and correcting the underlying cause or discontinuing any likely nephrotoxin. Serious sequelae are rare if the patient can drink at will.
Some drugs can lower urine output. Thiazide diuretics ( hydrochlorothiazide , 25 mg once/day or bid) can paradoxically reduce urine output by diminishing water delivery to ADH-sensitive sites in the collecting tubules. NSAIDs ( indomethacin ), amiloride , and a low-salt, low-protein diet can also be of benefit.
Last full review/revision November 2005
Content last modified November 2005
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