What is the purpose of water deprivation testing in patients with suspected diabetes insipidus (DI)?

From the Guidelines

Water deprivation testing should be avoided as a diagnostic procedure for congenital nephrogenic diabetes insipidus due to its potential harm and the availability of genetic testing as a safer and more accurate alternative. This diagnostic approach is supported by a recent international expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus, which emphasizes the importance of genetic testing in providing an early and definite diagnosis 1. The use of genetic testing can help identify patients with partial insensitivity to arginine vasopressin (AVP) and distinguish between central and nephrogenic diabetes insipidus, reducing the need for potentially harmful diagnostic procedures like water deprivation testing. Some key points to consider when evaluating the diagnosis of congenital nephrogenic diabetes insipidus include:

• Genetic testing can provide an early and definite diagnosis, avoiding unpleasant and potentially harmful diagnostic procedures 1
• A genetic diagnosis can help identify patients with partial nephrogenic diabetes insipidus and distinguish between central and nephrogenic diabetes insipidus 1
• Genetic testing can inform recurrence risks and support patient decision-making regarding family planning, including reproductive options such as prenatal and preimplantation genetic testing 1
• The identification of a genetic cause of nephrogenic diabetes insipidus can have implications for determining eligibility for future genetically stratified clinical trials 1. Given the potential risks associated with water deprivation testing, including severe hypertonic dehydration, seizures, developmental delay, and cognitive impairment, genetic testing is the recommended diagnostic approach for congenital nephrogenic diabetes insipidus 1.

From the Research

Water Deprivation Testing

• The water deprivation test is considered the gold standard for differentiating central or nephrogenic diabetes insipidus (DI) from primary polydipsia (PP) in patients with polyuria and polydipsia 2.
• A threshold for urine osmolality of >800 mOsmol/kg after water deprivation yielded a sensitivity and specificity of 96 and 100%, respectively, for diagnosing PP 2.
• The optimal cut-off value for differentiating PP from DI during a water deprivation test was urine osmolality >680 mOsmol/kg, which increased the sensitivity to 100% 2.
• Plasma arginine vasopressin (AVP) levels did not differ between patient groups and did not differentiate among central DI, nephrogenic DI, or PP 2.
• Copeptin (CP) levels were found to be <2.5 pmol/l in patients with central DI, and >2.5 pmol/l in patients without DI, suggesting a potential role for CP in differentiating DI from PP 2.

Dehydration and Its Treatment

• Dehydration is defined as the loss of body water, with or without salt, at a rate greater than the body can replace it 3.
• There are two types of dehydration: water loss dehydration (hyperosmolar) and salt and water loss dehydration (hyponatremia) 3.
• The diagnosis of dehydration requires an appraisal of the patient, laboratory testing, clinical assessment, and knowledge of the patient's history 3.

Other Studies

• A study on the effect of a 7-day treatment with idazoxan and its 2-methoxy derivative RX 821002 on alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites in rabbits found that the treatment increased the number of alpha 2-adrenoceptor binding sites in adipose tissue, but not in colocytes or platelets 4.
• This study suggests that alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites are two different entities, and that the treatment does not modify non-adrenoceptor idazoxan binding sites 4.