Nephrogenic Diabetes Insipidus (Bichet)
| Title: | Nephrogenic Diabetes Insipidus (Bichet) |
|---|---|
| Author: | Bichet, Daniel G. |
| Publisher: | Seminars in Nephrology |
| Date Published: | July 01, 1994 |
| Reference Number: | 100 |
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The primary clinical symptoms of X-linked NDI are polyuria (chronic passage of large volumes of urine) and polydipsia (chronic, excessive thirst). This form of NDI primarily affects males, and it may appear as early as the first week of life. The affected infant presents with irritability, failure to thrive, vomiting, fever, constipation, and high blood sodium levels. If he is not treated immediately, he could suffer bouts of extreme dehydration which could lead to physical and mental retardation.
Treatment consists of supplying the patient with adequate water intake to compensate for the water loss due to excessive urination. A low sodium diet along with administration of the diuretics, hydrochlorothiazide and indomethacin, help to substantially reduce urine excretion. As of yet, there is no known cure.
The molecular basis of X-linked NDI is mutations found in the vasopressin-2 receptor (V2R). The V2R is the protein that receives and binds with AVP. When this binding occurs a molecular sequence takes place that results in water-transporting proteins called aquaporin-2 inserting themselves in the apex of the principal cells of the kidney collecting duct. This is what allows the kidney to reabsorb water and concentrate urine in this portion of the tubule. Mutations of the V2R gene cause them to synthesize V2Rs with altered structures that negatively affect their ability to function. Researchers have found many different mutations of the V2R gene, each producing a differently altered, defective V2R.
Bichet encourages physicians following families with X-linked NDI to recommend mutational analysis well before the birth of an at-risk male infant, because early diagnosis and treatment of male infants affected with NDI can prevent or reduce the physical and mental retardation associated with the episodes of dehydration. Bichet notes that absence of family history of X-linked NDI does not rule out the disease and that measurements of plasma osmolality, plasma sodium, urine osmolality and response to a synthetic analog of AVP help diagnose NDI.
There is another form of inherited NDI caused by mutations of the AQP2 gene. This is a much rarer form of the disorder, equally able to affect male or female. And although the symptoms and treatment are identical, the response to the synthetic analog of AVP can help distinguish this form from the X-linked form.