What is the proper protocol for conducting a water deprivation test to diagnose diabetes insipidus?

Water Deprivation Test Protocol for Diagnosing Diabetes Insipidus

The water deprivation test should be conducted as a combined outpatient and inpatient overnight protocol to safely and effectively diagnose patients with polyuria-polydipsia syndrome, differentiating between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia. 1

Initial Assessment Before Testing

• Measure baseline serum sodium, serum osmolality, urine volume, and urine osmolality 2
• Consider measuring plasma copeptin levels as a surrogate marker for AVP - levels <21.4 pmol/l should prompt testing for AVP deficiency (central DI) 2, 3
• Rule out other causes of polyuria including poorly controlled diabetes mellitus (check for hyperglycemia and glucosuria) 4
• Genetic testing may help distinguish between central DI and nephrogenic DI, especially in cases with partial AVP insensitivity 4, 3

Water Deprivation Test Protocol

Preparation Phase

• Discontinue medications that can affect water metabolism (diuretics, prostaglandin inhibitors) at least 24 hours before the test 4
• Ensure normal sodium diet (≤6 g/day) for several days before testing 4
• Establish baseline weight, serum sodium, serum osmolality, and urine osmolality 1

Test Execution

1. Outpatient Phase:

   • Begin water restriction in the morning (typically 7-8 AM) 1
   • No fluid intake allowed throughout the test 1
   • Patient can remain ambulatory but should avoid excessive physical activity 1

2. Inpatient Overnight Phase:

   • Continue water restriction under medical supervision 1
   • Monitor weight, vital signs, and serum sodium levels regularly 1
   • Collect urine samples every 2-4 hours to measure osmolality 1, 5

3. Termination Criteria:

   • When one of the following is reached:

     • 3% reduction in body weight 5

     • Urinary specific gravity >1.020 or urinary osmolality >800 mOsm/L 5
     • Intolerable symptoms such as excessive thirst 5
     • Serum sodium exceeds safe levels (>148-150 mmol/L) 6
     • Maximum test duration of 16-18 hours 1, 5

4. DDAVP Administration:

   • After completing the water deprivation phase, administer desmopressin (DDAVP) 2
   • Collect urine samples at 30,60, and 120 minutes after DDAVP administration 6
   • Measure urine osmolality in each sample 6

Interpretation of Results

• Primary Polydipsia: Urine osmolality >680-800 mOsm/kg after water deprivation 5, 7
• Complete Central DI:
  • Urine osmolality remains <300 mOsm/kg after water deprivation 6

  • 50% increase in urine osmolality after DDAVP administration 6

  • Low or undetectable plasma AVP levels despite high serum osmolality 7
• Partial Central DI:
  • Intermediate urine concentration (300-800 mOsm/kg) after water deprivation 6
  • Significant increase in urine osmolality after DDAVP administration 6
• Nephrogenic DI:
  • Urine osmolality remains <300 mOsm/kg after water deprivation 6
  • <10% increase in urine osmolality after DDAVP administration 6
  • Elevated plasma AVP levels 1

Safety Considerations

• Close monitoring of serum sodium is crucial to prevent dangerous hypernatremia 1
• Have intravenous access available for emergency hydration if needed 1
• The test should be performed in experienced centers with appropriate supervision 1
• For patients requiring fasting >4 hours, consider intravenous 5% dextrose in water at maintenance rate if needed 4
• Monitor for signs of dehydration and electrolyte imbalances throughout the test 1

Alternative Diagnostic Approaches

• Hypertonic saline infusion test with copeptin measurement is emerging as a potentially safer and more accurate alternative 8, 6
• Arginine stimulation test with copeptin measurement may also be used as a confirmatory test 2
• In all three diagnostic approaches, the response to desmopressin remains a key differentiating factor between central and nephrogenic DI 2, 3