From the Guidelines
To evaluate nephrogenic diabetes insipidus (NDI), order serum sodium, serum osmolality, and urine osmolality as initial tests, as recommended by the international expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus (arginine vasopressin resistance) 1. These baseline measurements help establish the presence of dilute urine despite elevated serum osmolality. The key diagnostic test is the water deprivation test followed by desmopressin (DDAVP) administration. In this test, fluids are restricted until urine osmolality stabilizes, then DDAVP is given. In NDI, urine osmolality remains low despite DDAVP, unlike central diabetes insipidus where urine concentrates after DDAVP. Additional helpful tests include:
- Serum blood urea nitrogen (BUN)
- Creatinine
- Calcium
- Potassium
- Glucose to identify underlying causes or complications A 24-hour urine collection for volume and osmolality can document polyuria (>3L/day). Consider measuring antidiuretic hormone (ADH) levels, though this is more useful for central diabetes insipidus. These tests help differentiate NDI from central diabetes insipidus and primary polydipsia, guiding appropriate treatment for the specific condition, as outlined in the international expert consensus statement 1. Genetic testing can provide an early and definite diagnosis, with important implications for clinical management and outcome, and can avoid unpleasant, challenging, and potentially harmful diagnostic procedures, including the desmopressin (DDAVP) test or the water deprivation test 1. It is essential to consider the patient's clinical presentation, medical history, and family history when interpreting the results of these tests and developing a treatment plan. Regular follow-up with a multidisciplinary team, including a nephrologist, dietitian, psychologist, social worker, and urologist, is crucial for managing NDI and preventing complications 1.
From the FDA Drug Label
Laboratory tests for monitoring the patient include urine volume and osmolality In some cases, plasma osmolality may be required.
To evaluate nephrogenic diabetes insipidus, the following labs should be ordered:
- Urine volume
- Urine osmolality
- Plasma osmolality (in some cases) 2
From the Research
Diagnostic Approach
To evaluate nephrogenic diabetes insipidus, the following laboratory tests can be ordered:
- Water deprivation test to assess the ability to concentrate urine
- Baseline plasma copeptin measurement, a stable surrogate biomarker of AVP release 3, 4, 5
- Copeptin level measurement after stimulation with hypertonic saline infusion or arginine infusion to differentiate between central DI and primary polydipsia 4, 5
- Plasma AVP measurement to confirm the diagnosis of NDI
- Genetic testing to identify mutations in the AVPR2 or AQP2 genes, which can cause hereditary NDI 6, 7
- Electrolyte panel to evaluate for electrolyte abnormalities, which can be associated with secondary NDI 7
Laboratory Tests
The following laboratory tests can be used to support the diagnosis of NDI:
- Urinalysis to evaluate urine specific gravity and osmolality
- Serum osmolality to assess the degree of dehydration and hyperosmolality
- Electrolyte panel to evaluate for electrolyte abnormalities
- Blood urea nitrogen (BUN) and creatinine to assess renal function
Specialized Tests
In some cases, specialized tests may be ordered to support the diagnosis of NDI, including: