Nephrogenic Diabetes Insipidus

NDI can be

Generation of large amounts of dilute urine (3 to 20 L/day) is the hallmark. Patients typically have a good thirst response, and serum sodium remains near normal. However, patients who do not have good access to water or who cannot communicate thirst (eg, infants, older patients with dementia) typically develop hypernatremia Hypernatremia Hypernatremia is a serum sodium concentration > 145 mEq/L (> 145 mmol/L). It implies a deficit of total body water relative to total body sodium, caused by water intake being less than water... read more due to extreme dehydration. Hypernatremia may cause neurologic symptoms, such as neuromuscular excitability, confusion, seizures, or coma. Ureteral dilation is rare but can occur in severe cases with high urine volumes.

NDI is suspected in any patient with polyuria Polyuria Polyuria is urine output of > 3 L/day; it must be distinguished from urinary frequency, which is the need to urinate many times during the day or night but in normal or less-than-normal volumes... read more . In infants, polyuria may be noticed by the caregivers; if not, the first manifestation may be dehydration.

Initial testing includes 24-hour 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 (300 mmol/L; known as water diuresis), argininevasopressin deficiency or NDI is likely. With NDI, urine osmolality is typically < 200 mOsm/kg (200 mmol/L) despite clinical signs of hypovolemia (normally, urine osmolality is high in patients with hypovolemia). If osmolality is > 300 mOsm/kg (300 mmol/L), solute diuresis is likely. Glucosuria and other causes of solute diuresis must be excluded.

Serum sodium is mildly elevated (142 to 145 mEq/L, or 142 to 145 mmol/L) in patients with adequate free water intake but can be dramatically elevated in patients who do not have adequate access to free water.

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 delayed in affected children presumably because of frequent dehydration. All complications of NDI except for ureteral dilation are preventable with adequate water intake.

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 (eg, hydrochlorothiazide 25 mg orally once or twice/day) can paradoxically reduce urine output by diminishing water delivery to vasopressin-sensitive sites in the collecting tubules. NSAIDs (eg, indomethacin) or amiloride can also help.