What is Diabetes Insipidus (DI)?

From the Guidelines

Diabetes insipidus, specifically congenital nephrogenic diabetes insipidus, requires an integrated and multidisciplinary approach for diagnosis and management, as outlined in the recent international expert consensus statement 1. The condition is characterized by the kidney's insensitivity to arginine vasopressin, leading to an inability to concentrate urine, which results in polyuria, polydipsia, and a risk of hypertonic dehydration. Key aspects of management include:

• Diagnosis: Requires a comprehensive approach considering the patient's clinical presentation, laboratory findings, and genetic testing.
• Treatment: May involve the use of thiazide diuretics, such as hydrochlorothiazide, and other medications like amiloride or indomethacin to manage symptoms.
• Follow-up: Regular monitoring is crucial to adjust treatment as necessary and to prevent complications.
• Emergency management: It is essential to have a plan in place for managing acute situations, such as severe dehydration.
• Genetic counseling and family planning: Important for patients and their families to understand the genetic implications of the condition. According to the expert consensus statement 1, healthcare professionals should follow 36 recommendations for the diagnosis, treatment, and follow-up of patients with congenital nephrogenic diabetes insipidus, emphasizing the need for further research to support the development of evidence-based guidelines. The primary goal of treatment should be to improve the patient's quality of life by reducing polyuria and polydipsia, while also preventing complications such as dehydration 1.

From the FDA Drug Label

Desmopressin Acetate Injection is indicated as antidiuretic replacement therapy in the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Desmopressin acetate injection is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus. Diabetes Insipidus: Desmopressin acetate injection 4 mcg/mL is indicated as antidiuretic replacement therapy in the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region.

Diabetes Insipidus Treatment: Desmopressin acetate is indicated for the treatment of central (cranial) diabetes insipidus.

• It is not effective for the treatment of nephrogenic diabetes insipidus.
• The dosage must be determined for each patient and adjusted according to the pattern of response 2, 3.
• Key considerations:
  • Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover.
  • Fluid restriction should be observed.
  • The usual dosage range in adults is 0.5 mL (2 mcg) to 1 mL (4 mcg) daily, administered intravenously or subcutaneously, usually in two divided doses 3.

From the Research

Definition and Classification of Diabetes Insipidus

• Diabetes insipidus is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of more than 3 liters a day 4
• The two main classifications of diabetes insipidus are central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI) 4, 5
• Central diabetes insipidus is caused by insufficient production of vasopressin, while nephrogenic diabetes insipidus is caused by an impaired response of the kidneys to vasopressin 6

Etiology and Pathogenesis

• Central diabetes insipidus results from inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland 4
• Nephrogenic diabetes insipidus is linked to renal vasopressin resistance 7
• The etiology of diabetes insipidus can be due to genetic mutations of the AVP gene (central DI) or by mutations in the gene for the AVP V2R or the AQP2 water channel (nephrogenic DI) 4

Clinical Manifestations and Diagnosis

• Diabetes insipidus is marked by expelling excessive quantities of highly dilute urine, extreme thirst, and craving for cold water 5
• Differentiation between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia can be difficult, but different tests for differential diagnosis, such as measurement of copeptin, and a thorough medical history can lead to the correct diagnosis 4, 7
• Functional tests such as water deprivation or stimulation of copeptin by hyperosmolarity can be proposed to distinguish between different etiologies 7

Treatment and Management

• Treatment of central diabetes insipidus consists of fluid management and drug therapy with the synthetic AVP analogue Desmopressin (DDAVP) 4, 5
• The most common treatment of CDI and gestational DI is the administration of synthetic ADH, desmopressin (DDAVP) 5
• Nephrogenic treatment requires discontinuation of medications as well as maintaining a renal-friendly diet to prevent hypernatremia 5
• Main side effect of DDAVP therapy can be dilutional hyponatremia 4, 8