What medications can cause nephrogenic diabetes insipidus?

Medications That Cause Nephrogenic Diabetes Insipidus

Lithium is the most common medication causing nephrogenic diabetes insipidus (NDI), affecting approximately 10% of patients on long-term treatment (15 years), with other causative agents including foscarnet, clozapine, and various antimicrobials and cytostatics used in critically ill patients. 1

Common Causative Medications

First-Line Consideration

• Lithium: Most frequently reported cause of acquired NDI
  • Mechanism: Disrupts aquaporin-2 water channel function in the collecting ducts
  • FDA warning: "Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia" 2
  • Risk increases with duration of therapy and may be only partly reversible upon discontinuation 1

Other Significant Medications

• Antimicrobials:

  • Foscarnet (second most commonly reported) 1
  • Amphotericin B
  • Certain antibiotics

• Antipsychotics:

  • Clozapine (third most commonly reported) 1

• Other drug classes:

  • Chemotherapeutic agents
  • Certain antivirals

Diagnosis of Medication-Induced NDI

Drug-induced NDI can be diagnosed by:

• Water deprivation test (12 hours)
• Administration of desmopressin to demonstrate renal unresponsiveness 1
• Characteristic findings include:
  • Urine osmolality <200 mOsm/kg
  • Elevated serum sodium (>145 mmol/L)
  • Minimal/no increase in urine osmolality after desmopressin administration 3

Management Considerations

For Lithium-Induced NDI

1. Prevention strategies:

   • Close monitoring with 12-hour trough lithium levels of 0.4-0.6 mmol/L
   • Annual measurement of daily urinary volume 1
   • Consider alternative medications in high-risk patients

2. Treatment approaches:

   • First-line: Discontinuation of lithium when possible
   • Combination therapy for symptomatic management:
     • Thiazide diuretics (hydrochlorothiazide 25 mg once or twice daily)
     • Amiloride (particularly effective for lithium-induced NDI)
     • NSAIDs (e.g., indomethacin) for severe cases with urine volumes >4L/day 3, 1

3. Non-pharmacological management:

   • Unrestricted access to water to prevent dehydration
   • Low-salt diet (<6 g/day or 2.4 g sodium)
   • Low-protein diet (<1 g/kg/day) 3

Monitoring and Complications

• Regular laboratory monitoring:

  • Electrolytes (Na, K, Cl, HCO₃)
  • Renal function (creatinine, eGFR)
  • Uric acid levels
  • Urine osmolality 3

• Watch for complications:

  • Hypernatremic dehydration (medical emergency)
  • Urological complications (reported in 46% of NDI patients)
  • Hydronephrosis (reported in 34% of cases) 3

Important Clinical Pitfalls

1. Desmopressin is generally ineffective and not indicated for nephrogenic diabetes insipidus, though rare cases may show partial response when combined with other therapies 3, 4

2. Discontinuation of the causative medication may not fully reverse the condition, particularly with long-term lithium use 1

3. Hypernatremia correction should be limited to <8 mmol/L/day to prevent osmotic demyelination syndrome 3

4. Physical examination has poor sensitivity (41.1%) for determining volume status and should not be relied upon solely for diagnosis 3

By recognizing medications that commonly cause NDI and implementing appropriate monitoring strategies, clinicians can minimize the risk of this serious complication and optimize patient outcomes.