Diabetes insipidus, nephrogenic, dominant type

Diabetes Insipidus, Nephrogenic, Dominant Type

Diabetes insipidus, nephrogenic, dominant type (NDI) is a rare genetic disorder characterized by the kidney's inability to concentrate urine, leading to excessive urination and thirst. This condition is distinct from Diabetes Mellitus, which involves insulin and blood sugar regulation. NDI is caused by mutations in specific genes that affect the kidney's response to the hormone vasopressin, also known as antidiuretic hormone (ADH).

Pathophysiology

In normal physiology, vasopressin binds to receptors in the kidney, promoting water reabsorption and concentrating urine. In nephrogenic diabetes insipidus, the kidneys are unable to respond to vasopressin due to mutations in the genes encoding the vasopressin receptor (AVPR2) or aquaporin-2 (AQP2) water channels. The dominant type of NDI is typically associated with mutations in the AVPR2 gene, which is located on the X chromosome. This gene encodes the V2 vasopressin receptor, which is crucial for the kidney's ability to concentrate urine.

Genetics

NDI can be inherited in an X-linked dominant pattern, meaning that a single copy of the mutated gene on the X chromosome can cause the disorder. This form of inheritance is unusual because it can affect both males and females, although males are often more severely affected due to having only one X chromosome.

Clinical Presentation

Patients with NDI present with polyuria (excessive urination) and polydipsia (excessive thirst). These symptoms can lead to dehydration and electrolyte imbalances if fluid intake does not match urine output. In infants, symptoms may include irritability, poor feeding, and failure to thrive.

Diagnosis

Diagnosis of NDI involves a combination of clinical evaluation, laboratory tests, and genetic testing. A water deprivation test can help differentiate between central and nephrogenic diabetes insipidus. Genetic testing can confirm mutations in the AVPR2 or AQP2 genes.

Management

Management of NDI focuses on maintaining adequate hydration and electrolyte balance. Patients are advised to drink sufficient fluids to match urine output. Thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) may be used to reduce urine volume. In some cases, a low-salt, low-protein diet is recommended to decrease solute load and urine output.

Prognosis

With appropriate management, individuals with NDI can lead normal lives. However, ongoing monitoring and management are necessary to prevent complications such as dehydration and kidney damage.

Also see

• Diabetes Insipidus
• Vasopressin
• Aquaporin
• X-linked Dominant Inheritance