Urinary Excretion of Aquaporin-2 in Patients with Diabetes Insipidus
| Title: | Urinary Excretion of Aquaporin-2 in Patients with Diabetes Insipidus |
|---|---|
| Authors: | Kanno, MD, Kazuo; Sasaki, Sei; Hirata, MD, Yukio; Ishikawa, San-e; Fushimi, MD, Kiyohide; Nakanishi, PhD, Setsuko; Bichet, Daniel G.; Marumo, MD, Fumiaki |
| Publisher: | New England Journal of Medicine |
| Date Published: | June 08, 1995 |
| Reference Number: | 63 |
BACKGROUND: Urine-concentrating ability is regulated by vasopressin. Recently, the specific water-channel protein of the renal collecting duct, known as aquaporin-2, was cloned. However, it is not certain whether this molecule is responsive to vasopressin.
METHODS: We measured the urinary excretion of aquaporin-2 and its response to vasopressin in 11 normal subjects and 9 patients with central or nephrogenic diabetes insipidus. The urine samples were collected during periods of dehydration and hydration and after the administration of vasopressin. Urine samples were analyzed for aquaporin-2 by the Western blot assay and immunogold labeling, and the amount of aquaporin-2 was determined by radioimmunoassay.
RESULTS: Aquaporin-2 was detectable in the urine in both soluble and membrane-bound forms. In the five normal subjects tested, the mean (+/- SE) urinary excretion of aquaporin-2 was 11.2 +/- 2.2 pmol per milligram of creatinine after a period of dehydration, and it decreased to 3.9 +/- 1.9 pmol per milligram of creatinine (P = 0.03) during the second hour after a period of hydration. In the six other normal subjects, an infusion of desmopressin (1-desamino-8-D-arginine vasopressin) increased the urinary excretion of aquaporin-2 from 0.8 +/- 0.3 to 11.2 +/- 1.6 pmol per milligram of creatinine (P < 0.001). The five patients with central diabetes insipidus also had increases in urinary excretion of aquaporin-2 in response to the administration of vasopressin, but the four patients with X-linked or non-X-linked nephrogenic diabetes insipidus did not.
CONCLUSIONS: Aquaporin-2 is detectable in the urine, and changes in the urinary excretion of this protein can be used as an index of the action of vasopressin on the kidney.
METHODS: We measured the urinary excretion of aquaporin-2 and its response to vasopressin in 11 normal subjects and 9 patients with central or nephrogenic diabetes insipidus. The urine samples were collected during periods of dehydration and hydration and after the administration of vasopressin. Urine samples were analyzed for aquaporin-2 by the Western blot assay and immunogold labeling, and the amount of aquaporin-2 was determined by radioimmunoassay.
RESULTS: Aquaporin-2 was detectable in the urine in both soluble and membrane-bound forms. In the five normal subjects tested, the mean (+/- SE) urinary excretion of aquaporin-2 was 11.2 +/- 2.2 pmol per milligram of creatinine after a period of dehydration, and it decreased to 3.9 +/- 1.9 pmol per milligram of creatinine (P = 0.03) during the second hour after a period of hydration. In the six other normal subjects, an infusion of desmopressin (1-desamino-8-D-arginine vasopressin) increased the urinary excretion of aquaporin-2 from 0.8 +/- 0.3 to 11.2 +/- 1.6 pmol per milligram of creatinine (P < 0.001). The five patients with central diabetes insipidus also had increases in urinary excretion of aquaporin-2 in response to the administration of vasopressin, but the four patients with X-linked or non-X-linked nephrogenic diabetes insipidus did not.
CONCLUSIONS: Aquaporin-2 is detectable in the urine, and changes in the urinary excretion of this protein can be used as an index of the action of vasopressin on the kidney.
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)
Kanno, et al., designed an experiment to determine whether or not AQP2 is responsive to VP. They studied four groups of subjects:
1. five normal males
2. three females and two males with central diabetes insipidus (CDI)
3. four males with nephrogenic diabetes insipidus (NDI)
4. two normal females and four normal males
First, the researchers determined that intact AQP2 was excreted in the urine. AQP2 was also excreted in the urine while bound to CD cell membranes. Thus, the researchers could check the levels of AQP2 in the urine of their subjects as a measure of AQP2 response to their experimental conditions.
The first group of five normal subjects showed increased levels of urinary AQP2s in response to an overnight period of dehydration brought on by being restricted from liquid for that period. Group four, the six other normal subjects, showed increased levels of urinary AQP2 excretion after being injected by a synthetically modified form of VP called DDAVP. The five CDI patients also increased urinary levels of AQP2 in response to DDAVP. But the four NDI patients did not.
Urinary excretion of AQP2 increased in normal subjects in a state where urination was suppressed either through dehydration or infusions of DDAVP. The researchers explain that VP increases the movement of AQP2 to the apical membrane and that some of the apical membranes get sloughed off into the urine. Dehydration increases circulating VP. DDAVP acts as VP does, and it was given in doses that would induce movement of AQP2 to the apical membrane.
The patients with CDI showed increased urinary AQP2 expression in response to VP. CDI patients do not produce VP on their own and require infusions of VP to concentrate urine. The patients with NDI showed no increase in urinary levels of AQP2 in response to DDAVP. NDI patients do produce VP but their kidneys do not respond to it.
The results of the authors experiments show
1. AQP2 is detectable in urine
2. AQP2 does respond to VP
3. urinary excretion of AQP2 can act as an index of the action of VP on the kidney.
The authors suggest that the response to DDAVP in terms of urinary excretion of AQP2 may be one way to differentiate between patients with CDI and patients with NDI.