Desmopressin for Nocturnal Enuresis in Nephrogenic Diabetes Insipidus
| Title: | Desmopressin for Nocturnal Enuresis in Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Muller, Dominik; Marr, Nannette; Ankermann, Tobias; Eggert, Paul; Deen, Peter M.T. |
| Publisher: | The Lancet |
| Date Published: | February 09, 2002 |
| Reference Number: | 532 |
We have investigated two unrelated families, in which two children had inherited primary nocturnal enuresis, and nephrogenic diabetes insipidus caused by new mutations in the aquaporin-2 gene (AQP2). The mutant AQP2 proteins were inactive, suggesting that administration of desmopressin could not concentrate the urine in these patients. However, treatment with desmopressin resolved primary nocturnal enuresis completely. This observation questions the notion that desmopressin resolves primary nocturnal enuresis through pharmacological manipulation of renal concentrating ability only. Desmopressin might also act on extrarenal targets such as the central nervous system.
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 researchers worked with three children with primary nocturnal enuresis, two of whom also had congenital nephrogenic diabetes insipidus (NDI). NDI patients cannot concentrate their urine, generally due to a mutation in either their vasopressin-2 receptor (V2R) gene or their aquaporin-2 (AQP2) gene. Normally, AVP binds with V2R and this initiates a cascade of molecular events that signal AQP2 to travel from the interior of the kidney collecting duct principal cells to the cell membrane. Once in the membrane, the cell is able to let water pass through it, which is how the kidney concentrates urine.
NDI patients normally have normal amounts of AVP in their systems; however, it is rendered ineffective through either AQP2 or V2R gene mutations. Thus, desmopressin, which is a synthetic form of AVP, should have no effect in helping a NDI patient reduce urine.
In this study all three children were tested with desmopressin. As expected, the child with only nocturnal enuresis responded with more concentrated urine, and the two children with nocturnal enuresis as a result of their NDI did not. However, when all three began desmopressin treatment, all three stopped wetting their bed during the night within two days. The child with primary nocturnal enuresis would sleep through the night without incident, and the two children with NDI would wake up during the night to go to the bathroom. When the treatment was stopped, the bedwetting would reoccur. When treatment was restarted, the bedwetting would cease. This suggests that desmopressin does not stop primary nocturnal enuresis by affecting the kidney's ability to concentrate urine. The researchers suggest it affects the central nervous system in a manner which puts an end to nighttime bedwetting.