Do Aquaporins Have a Role in Nocturnal Enuresis?

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Title: Do Aquaporins Have a Role in Nocturnal Enuresis?
Authors: Frokiaer, Jorgen; Nielsen, Soren
Publisher: Scandinavian Journal of Urology and Nephrology. Supplementum.
Date Published: 1997
Reference Number: 186
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Abstract • Article • Translation
Aquaporins are proteins that mediate transmembrane water transport in a variety of tissues including the kidney. Vasopressin plays an important role in regulation of water metabolism, and under normal conditions the kidney collecting duct is extremely sensitive to vasopressin. Vasopressin stimulates the synthesis of aquaporin 2 (AQP2) in kidney collecting duct principal cells. Studies in Brattle Boro rats which are vasopressin deficient, revealed low levels of AQP2 in association with extreme polyuria. After vasopressin treatment for 5 days AQP2 levels increased threefold. Using rat models with nephrogenic diabetes insipidus (NDI) we have demonstrated that AQP2 expression is down regulated in association with polyuria, suggesting that reduced levels of AQP2 may be a general factor in acquired forms of NDI from a variety of reasons. The polyuria and urinary concentrating defects associated with an abnormal nightly-increase in AVP in patients with nocturnal enuresis may partly be due to a lack of vasopressin-mediated AQP2 expression since treatment with desmopressin in these patients have normalised their nocturnal urine production.
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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)

Aquaporin-2 (AQP2) is a water-transporting protein located in the principal cells of the kidney collecting duct. When signaled by the antidiuretic hormone, arginine vasopressin (AVP), AQP2s travel from their holding place inside the collecting duct cells and insert themselves in the apex of the membranes of these cells. This allows a great deal more water to pass through these cells than normal, and this is how the kidney is able to reabsorb water through the collecting duct. What water is not reabsorbed is the concentrated urine that travels from the kidney to the bladder by means of a tube called the ureter.

That AQP2 expression is dependent on AVP is made clear in the case of nephrogenic diabetes insipidus (NDI), which is caused by the kidneys inability to respond to AVP. Studies of BrattleBoro rats, which are a breed of rats who do not produce sufficient levels of AVP, reveal low levels of AQP2 in association with polyuria (the chronic passage of large volumes of urine). When these rats are injected with a synthetic AVP analog over a five day period, AQP2 levels increase three-fold. Other studies of rats with NDI show a reduced expression of AQP2 in association with polyuria. But even though it is clear that AQP2 is AVP-sensitive, the author's research also suggests other mechanisms, such as blockage of ureters, also influence AQP2 expression.

When both ureters are blocked in rats, their urine production is blocked and a period of polyuria results after the release of the obstruction. This bilateral obstruction produced a dramatic decrease in AQP2 expression which was maintained for seven days after the obstruction was removed. After this seven-day period, the AQP2 expression increased and the rats' polyuria ended. Obstructing only one uterer in rats also lowers AQP2 expression. And these low levels of AQP2 expression appeared, to a lesser degree, in the kidneys connected to the uterers that were not blocked. These experiments were also performed on BrattleBoro rats with the same effect. Since these rats are AVP deficient, the findings suggest other mechanisms than AVP also influence AQP2 expression.

Frokiaer and Nielsen note that polyuria may be caused by defects of the central nervous system, the kidney or the urinary tract. They suggest that all types of polyuria may ultimately result from the degree to which AQP2s are expressed in the kidney collecting duct. To that end, they have developed a method to measure the amount of AQP2 excreted in the urine in order to help study patients with involuntary discharge of urine during the night.