Water Deprivation Test
Principle: dehydrate till ADH secretion concentrates urine
Used in differential diagnosis of polyuria, separating Cranial Diabetes Insipidus (CDI), Nephrogenic Diabetes Insipidus (NDI) and Primary Polydipsia/Compulsive Water Drinking (PP).
If in the basal state plasma osmolality > 295 mosmol/kg, plasma Na > 145 mmol/l and urine is hypotonic (< 300 mosmol/kg), PP is excluded and investigation goes straight to DDAVP administration.
Exclude other causes of polyuria: diuretics, chronic renal failure, hypercalcaemia, hypokalaemia.
Anterior pituitary hormone deficiency: renders results meaningless as, in particular, steroid and thyroxine deficiencies impair excretion of a free water load.
Up to 8.30 hrs:
- No tobacco/alcohol for 24 hrs before the test
- Stop interfering medication (e.g. DDAVP (last dose 24 hours before the start of the test), diuretics) but not hormone replacement
- Light breakfast (do not fast or limit fluids overnight).
- Blood is taken into yellow top Vacutainers, urine into Sterilin universal containers
- urine measuring jug.
- DDAVP: if given intranasally, must acquaint yourself with the spray as it is not easy to use.
Supervision by nursing staff or SHO is essential.
If true CDI or NDI, risk of excessive dehydration.
Stage 1 (exclusion of PP): 8.30 - 16.30 hrs
1. No fluid allowed but dry food permitted (e.g. toast)
2. Weigh patient at time 0 and hourly intervals: stop test if >3% weight loss (positive test)
3. Urine passed and discarded at time 0; urine then passed hourly and hourly volume estimated
4. Urine specimen taken for osmolality from the total hourly sample passed over 8.30 - 9.30hrs (U1), 11.30 - 12.30 (U2), 14.30 - 15.30 (U3), 15.30 - 16.30 (U4)
5. Blood taken for osmolality at 9.00hrs (P1), 12.00 (P2), 15.00 (P3), 16.00 (P4)
6. Note down urine volumes in chart as shown below (U1-U4).
Stage 2 (differential diagnosis CDI from NDI): 16.30 - 20.30 hrs
7. Patient may now eat and drink freely
8. At 16.30 hrs, administer DDAVP: 20 mcg intra-nasally or 2 mcg i.m.
9. Continue to measure hourly urine volumes and take samples for osmolality from each hourly sample. There is no point measuring plasma samples (or taking any blood), as the patient are now eating and drinking freely, and we are only interested in the effects of the administered DDAVP on urine volume and osmolality.
10. Note down urine volumes in chart as shown below (U5-U8).
TIME URINE / VOLUME PLASMA
0830 Discard urine
0900 Þ Collect P1
0930 Collect U1 ml
1130 Discard urine
1200 Þ Collect P2
1230 Collect U2 ml
1430 Discard urine
1500 Þ Collect P3
1530 Collect U3 ml
1600 Þ Collect P4
1630 Collect U4 ml
Now give DDAVP i.m. or intranasally
1730 Collect U5 ml
1830 Collect U6 ml
1930 Collect U7 ml
2030 Collect U8 ml
With dehydration, plasma is concentrated but to <300 mosmol/kg. Urine also concentrates to >600 mosmol/kg
2) PP or partial DI
Start with a low plasma osmolality, which concentrates to normal during stage 1. Urine concentrates, though may be subnormal response (see below).
Patient excessively concentrates plasma to >300 mosmol/kg with inappropriately hypotonic urine (U3:P3 or U4:P4 = <1.9). After DDAVP: CDI patient, deficient in ADH, is still able to concentrate urine to >150% of previous highest level. In NDI, patient is unable to respond to ADH or DDAVP, and concentrates urine to <150% of previous highest value.
Diagnosis After dehydration After DDAVP
Normal >750 >750
PP or partial CDI/NDI 300-750 <750
CDI <300 >750
NDI <300 <300
Urine osmolality (mosmol/kg)
If there is a partial response, this test does not reliably differentiate between PP and partial CDI or NDI because the response to dehydration and DDAVP may be very similar:
- Polyuria of any origin (e.g. PP or CDI) washes out medullary concentration gradient, blunting maximal urinary concentration
- CDI may increase renal sensitivity to very low levels of AVP. If patient has only a partial deficiency of AVP, dehydration may therefore rapidly increase urine osmolality to maximum of which they are capable.
- Some patients with NDI can concentrate urine if plasma AVP increases to supra-physiological levels, e.g. with exogenous DDAVP.
IF THERE IS A PARTIAL RESPONSE, FURTHER INVESTIGATION IS INDICATED.
SENSITIVITY AND SPECIFICITY
When well performed, the WDT has a sensitivity and specificity of 95% for diagnosing and differentiating severe CDI and NDI. The incidence of false positive and false negative results for PP or partial CDI/NDI is 30-40% (investigate further).
Vokes et al., Endo. Metab. Clin. N. Amer. 17(2), 281 (1988).