Normal physiologic response to the water deprivation will increase plasma osmolality, which will then lead to a progressive elevation in ADH release and an increase in urine osmolality. Once the plasma osmolality reaches 295 " “300 mOsm/kg (normal: 275 " “290 mOsm/kg), the effect of endogenous ADH on the kidney is maximal. At this point, administering ADH does not further elevate the urine osmolality unless endogenous ADH release is impaired (e.g., the patient has central diabetes insipidus [DI]). This test is also known as the water restriction test.
Normal response: Water deprivation causes kidney to increase urine osmolality to 1,000 " “1,200 mmol/kg. ADH does not cause further increase in urine osmolality because endogenous ADH is already at maximum.
Use
To distinguish the major forms of DI " ”neurogenic, nephrogenic, and polydipsic.
Steps:
Have the patient should stop drinking 2 " “3 hours before coming to the office or clinic; overnight fluid restriction should be avoided, because potentially severe volume depletion and hypernatremia can be induced in patients with marked polyuria.
Collect 7 " “10 mL of heparinized blood for immediate measurements of serum sodium concentration and osmolality. Also ask the patient to void his/her bladder, record the urine volume, and send urine specimen for immediate measurement of osmolality.
Repeat step 2 every hour until (a) plasma sodium concentration or osmolality rises above the upper limit of normal range or (b) urine osmolality rises above 300 mOsm/kg H2O.
If (a) occurs before (b), primary polydipsia, partial neurogenic, and partial nephrogenic DI are excluded, and a dDAVP (synthetic analog of ADH) challenge test should be done as follows:
Inject 2 ˇ ¼g of dDAVP subcutaneously.
Ask the patient to empty bladder at 1 and 2 hours after the injection; measure the urine osmolality. Also measure the patients plasma ADH level.
If either urine samples has an osmolality >50% higher than the value immediately before injection, the patient probably has complete neurogenic DI.
If both urine samples have osmolality increase of <50% than the value immediately before injection, the patient is very likely to have complete nephrogenic DI.
If (b) occurs before (a), complete neurogenic and nephrogenic DI are excluded. Further differentiate among partial nephrogenic DI, partial neurogenic DI, and primary polydipsia will require trained personnel and specialized measurements.
Interpretation
Complete DI: Water deprivation increases plasma osmolality but urine osmolality stays <290 mmol/kg and does not increase following dDAVP challenge.
Partial DI: Water deprivation causes some increase in urine osmolality to 400 " “500 mmol/kg (less than normal).
Complete or partial nephrogenic DI or psychogenic polydipsia: Increased ADH levels. Giving ADH does not increase urine osmolality in complete nephrogenic DI.
Complete or partial neurogenic DI: Low ADH relative to plasma osmolality. Giving ADH increases urine osmolality approximately 200 mmol/kg but not in partial nephrogenic DI.
Limitations
Some nonosmotic stimuli, such as smoking, hypotension, and nausea, can increase ADH release. If a transient episode of hypotension and nausea occurs, the entire test is invalid and it needs to be repeated in another day.
Complete emptying of the bladder during each collection is important because incomplete emptying may dilute the urine of the next collection.
The plasma sample for osmolality measurement should be from heparinized blood, and EDTA should be avoided because it artificially increases the osmolality by 3 " “10%.
The plasma for ADH measurement should be collected without disturbing the buffy coat in order to minimize the contamination from platelets.
The test should be performed only when the patients basal plasma sodium concentration is within the normal range, otherwise it may cause potential harm to the patient.
The test should not be performed in patients with renal insufficiency, uncontrolled DM, or hypovolemia of any cause or uncorrected adrenal or thyroid hormone deficiency.
Patients should be observed for the entire duration of the test.
For pregnant patients, the blood sample for ADH measurement should be drawn into a tube that contains 6 mg of 1,10-phenanthroline to prevent the degradation of ADH by placental vasopressinase. The results should be evaluated in the context of altered relationship between the plasma osmolality/sodium concentration and the plasma ADH concentration.