Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus is partial or complete resistance of the renal collecting duct to antidiuretic hormone, most often from chronic lithium therapy, hypercalcemia, or hypokalemia in adults, producing dilute polyuria and compensatory polydipsia. Diagnosis rests on hypernatremia with inappropriately dilute urine that fails to concentrate after desmopressin, and management is stopping the offending drug or correcting the electrolyte abnormality when possible plus a low-sodium, low-protein diet with a thiazide diuretic, adding amiloride if polyuria persists or lithium must continue.
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What this article covers
- Overview
A disorder of partial or complete unresponsiveness of the renal collecting-duct cells to antidiuretic hormone (ADH, vasopressin), so the kidney fails to concentrate urine despite normal or elevated circulating ADH.
- Epidemiology
Rare overall, with acquired nephrogenic DI far outnumbering the congenital form.
- Risk factors
Chronic lithium therapy, the leading acquired cause, with risk rising with cumulative duration of use.
- Pathophysiology
ADH normally binds the V2 receptor on the basolateral membrane of collecting-duct principal cells, triggering insertion of aquaporin-2 water channels into the luminal membrane; this insertion is the step disrupted in nephrogenic DI.
- Clinical features
Polyuria and polydipsia are the defining features, with a preference for ice-cold water and urine that appears pale or colorless from dilution.
- Differential diagnosis
Central diabetes insipidus: shares polyuria, polydipsia, and hypernatremia with dilute urine, but distinguished by a rise in urine osmolality of more than 50% after desmopressin, unlike the absent response in nephrogenic DI.
- Diagnosis
The diagnosis is established by hypernatremia (serum sodium 145 mEq/L) with an inappropriately low urine osmolality (<150 mOsm/kg) in a patient not receiving aquaretic medications, which is…
- Management
First, correct any life-threatening volume depletion: if the patient is orthostatic or hypotensive, resuscitate with a hypotonic fluid such as D5W or one-quarter isotonic saline, since…
- Complications
Hypernatremic dehydration, ranging from mild volume contraction to severe hypertonic encephalopathy if water losses are not matched by intake.
- Prognosis
Acquired nephrogenic DI due to hypercalcemia or hypokalemia typically resolves once the electrolyte abnormality is corrected, restoring normal urine-concentrating ability.
- Prevention
Monitor serum lithium levels regularly (typically every 3-6 months in stable patients) and use the lowest effective dose to reduce cumulative nephrotoxic exposure.
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Related articles
- Central diabetes insipidus
Central diabetes insipidus is inability of the posterior pituitary to produce adequate antidiuretic hormone, causing free water loss, polyuria, and hypernatremia; common causes include pituitary/hypothalamic tumor, surgery, trauma, and infiltrative disease. Diagnosis is confirmed with a water deprivation test followed by a desmopressin challenge, and treatment is desmopressin (DDAVP) 10-40 mcg intranasally or 0.1-0.4 mg orally, dosed once nightly or twice daily and titrated to control polyuria while avoiding dilutional hyponatremia from over-replacement.
- Syndrome of inappropriate antidiuretic hormone (SIADH)
SIADH is euvolemic hypotonic hyponatremia caused by antidiuretic hormone secretion or action that is inappropriate for the patient's osmotic and volume status. First-line treatment is fluid restriction to about 800-1,000 mL/day, with vasopressin receptor antagonists (vaptans) or hypertonic saline reserved for severe or symptomatic hyponatremia resistant to fluid restriction.
- Hypercalcemia
Hypercalcemia is an elevated serum calcium concentration, most often caused by primary hyperparathyroidism in ambulatory patients or malignancy in hospitalized patients. Mild disease requires only treatment of the underlying cause, while severe or symptomatic hypercalcemia is treated with aggressive IV isotonic fluids, followed by an IV bisphosphonate or denosumab for sustained control and subcutaneous calcitonin as a rapid but short-lived bridge.