The Clinical Importance of the Urinary Excretion of Aquaporin-2
| Title: | The Clinical Importance of the Urinary Excretion of Aquaporin-2 |
|---|---|
| Authors: | Knoers, Nine; van Os, Carel |
| Publisher: | New England Journal of Medicine |
| Date Published: | June 08, 1995 |
| Reference Number: | 253 |
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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)
In the disorder known as nephrogenic diabetes insipidus (NDI), the AQP2s are unable to perform these functions, leaving the NDI patient chronically thirsty and in need of voiding large volumes of dilute urine on a daily basis.
Kanno, et al., report that AQP2 is detectable in urine in two forms: dissolved in the urine and still bound to cell membranes. They found that dehydrating normal test subjects by restricting them from water for a period of time, or infusing the test subjects with DDAVP, a synthetically modified form of VP, significantly increased the subjects' urinary excretion. This is because both dehydration and DDAVP increase the level of VP circulating through the system. And this increase results in increased AQP2 in the apical membrane, some of which gets carried out in the urine. Thus, Kanno, et al, suggest that urinary AQP2 reflects the regulation of AQP2 by VP.
These researchers also discovered that test subjects with central diabetes insipidus (CDI) - a disorder caused by a lack of VP circulating in the body - had low urinary AQP2 during dehydration, but high urinary AQP2 after injections of VP. This is because the VP initiated AQP2s to insert themselves in the apical membrane of the principal CD cells. And some of the AQP2s so inserted end up in the urine.
In patients with NDI, there was no increase in the excretion of AQP2 in the urine in response to injections of synthetically modified VP. Kanno, et al., conclude that urinary excretion of AQP2 could be used to help clinicians differentiate between CNDI and CDI.
Knoers and van Os respond by noting that NDI and CDI can be easily differentiated by measuring urinary osmolality in response to intranasal administration of DDAVP. NDI patients will show no increase in urine osmolality, whereas CDI patients will show a substantial increase. But Knoers and van Os support the idea of using urinary excretion of AQP2 as an index of the action of VP in the kidney. As an example they site the fact that long term use of lithium in rats causes a marked decrease in the expression of AQP2s. This results in severe NDI. They suggest measuring the urinary excretion levels of AQP2 in people receiving long-term lithium treatment. Long-term lithium use is known to cause NDI in about 20% of patients taking it. If measurements revealed long-term lithium patients showed a decrease in AQP2 in their urine, then perhaps urinary excretion of AQP2 could act as a method of examining whether other instances of secondary NDI such as those caused by use of tetracyclines, or cases of hypokalemia, hypercalcemia, juvenile nephronophthisis or post-obstructive diuresis, are also associated with reductions in either the expression of AQP2 or its delivery to the apical membrane.