Urinary Excretion of Aquaporin-2 in Humans: A Potential Marker of Collecting Duct Responsiveness to Vasopressin

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Title: Urinary Excretion of Aquaporin-2 in Humans: A Potential Marker of Collecting Duct Responsiveness to Vasopressin
Authors: Elliot, Sharon; Goldsmith, Paul K.; Knepper, Mark; Haughey, Mary; Olson, Beatriz
Publisher: Journal of the American Society of Nephrology
Date Published: March 01, 1996
Reference Number: 350
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The vasopressin-sensitive water channel (aquaporin 2; AQP-2) mediates water transport across the apical plasma membrane of the renal collecting ducts and is excreted in human urine. This study presents the hypothesis that measurements of the AQP-2 excretion rate might be used as a marker of collecting-duct responsiveness to vasopressin, and therefore could be useful in the clinical evaluation of various water-balance disorders. This study presents information about the development of an antibody to human AQP-2, and measures the urinary excretion of AQP-2 by quantitative Western analysis. A standard curve of band densities was generated by using known quantities of the modified immunizing peptide to derive the amount of AQP-2 contained in aliquots of urine. AQP-2 urinary excretion changed with short-term alterations in hydration status produced either by water loading (76% decrease, P < 0.01) or by 3% sodium chloride (760% increase, P < 0.01). Steady-state 24-h urinary excretion of AQP-2 was 43 +/- 10 nmol/24 h (or 28.5 +/- 6.9 pmol/mg creatinine), and 20 +/- 6 nmol/24 h (or 18.3 +/- 7.9 pmol/mg creatinine) in men and women, respectively. Therefore, urinary AQP-2 excretion can be quantified by using Western analysis, and may serve as a marker of collecting-duct responsiveness to vasopressin in different physiologic settings.
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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.
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Aquaporin-2 (AQP2) is a membrane protein located in the principal cells of the kidney collecting duct (CD). It sits within the cell in little sacs called vesicles. When stimulated by the antidiuretic hormone, arginine vasopressin (AVP), the AQP2-bearing vesicles travel from within the cell to the apical membrane of the cell. Once there, they fuse with it and the AQP2s are inserted. The AQP2s allow more body water to flow across the apical membrane than usual. This is vital to the urine concentrating process as it allows the body water flowing through the CD to be reabsorbed into the kidneys' inner tissue.

AQP2 is excreted in human urine, a fact which led Elliot, et al., to hypothesize that measurements of the AQP2 urinary excretion rate might be able to be used as an indicator of CD responsiveness to AVP. If so, the AQP2 excretion rate could prove useful in the clinical evaluation of various water-balance disorders.

To test their hypothesis, the authors developed a method of measuring the amount of AQP2 in urine, and they first measured the amount of AQP2 in the urine of healthy male and female volunteers over a 24 hour time period. Then they placed the volunteers in a hydrated state by restricting them from water for a period of time. And finally, they placed the volunteers in a water loaded state. The authors collected urine samples during these extremes of dehydration and of super hydration in order to see whether these short-term osmotic alterations resulted in corresponding changes in AQP2 urinary excretion. If they did, then it would suggest that AQP2 urinary excretion levels could be used as a marker of CD responsiveness to AVP.

The dehydrated state creates an osmotic condition that calls forth more AVP, which stimulates AQP2 to move to the CD cell apical membranes. The water-loaded state decreases osmolality, which suppresses AVP secretion. Thus, there is no AVP to stimulate AQP2s into action.

AQP2 urinary excretion was primarily detectable during water deprivation as compared with water-loaded conditions. Since the authors found that the short-term osmotic changes they induced in the volunteers produced extracellular fluid and AVP levels that corresponded with changes in AQP2 excretion (detectable urinary AQP2 during hydration, but not during water-loading), the authors suggest that measurement of urinary AQP2 may help clinicians assess the kidney CD response to AVP in different physiologic conditions.