Urinary excretion of the water channel aquaporin 2 correlated with the pharmacological effect of tolvaptan in cirrhotic patients with ascites

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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Urinary excretion of the aquaporin-2 water channel exaggerated in pathological states of impaired water excretion

Clinical Endocrinology ◽

10.1046/j.1365-2265.2001.01336.x ◽

2001 ◽

Vol 55 (2) ◽

pp. 217-221 ◽

Cited By ~ 4

Author(s):

Takako Saito ◽

Minori Higashiyama ◽

Tomoatsu Nakamura ◽

Ikuyo Kusaka ◽

Shoichiro Nagasaka ◽

...

Keyword(s):

Urinary Excretion ◽

Water Channel ◽

Water Excretion ◽

Aquaporin 2 ◽

Impaired Water

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Urinary Excretion of Aquaporin-2 Water Channel is Dominant in Pathological State of Arginine Vasopressin-Induced Impaired Water Excretion

Molecular Biology and Physiology of Water and Solute Transport ◽

10.1007/978-1-4615-1203-5_29 ◽

2000 ◽

pp. 209-214

Author(s):

Sane Ishikawa ◽

Takako Saito ◽

Akinori Fukagawa ◽

Tomoatsu Nakamura ◽

Ikuyo Kusaka ◽

...

Keyword(s):

Urinary Excretion ◽

Arginine Vasopressin ◽

Water Channel ◽

Pathological State ◽

Water Excretion ◽

Aquaporin 2 ◽

Impaired Water

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Urinary excretion of aquaporin-2 water channel protein in human and rat.

Journal of the American Society of Nephrology ◽

10.1681/asn.v891357 ◽

1997 ◽

Vol 8 (9) ◽

pp. 1357-1362 ◽

Cited By ~ 1

Author(s):

T Rai ◽

K Sekine ◽

K Kanno ◽

K Hata ◽

M Miura ◽

...

Keyword(s):

Urinary Excretion ◽

Water Channel ◽

Urine Osmolality ◽

Urine Samples ◽

Spot Urine ◽

Aquaporin 2 ◽

Wide Range ◽

Daily Excretion ◽

The Mean ◽

High Concentrations

Previous studies by the authors demonstrated that the response of urinary aquaporin-2 (AQP2) excretion to dDAVP (deamino-8-D-arginine vasopressin) infusion is an index of vasopressin action on the kidney (N Engl J Med 332: 1540-1545, 1995). In the study presented here, the characteristics of urinary excretion of AQP2 were examined further. An RIA suitable for AQP2 in the urine was established. Relatively high concentrations of detergent and bovine serum albumin in the RIA buffer allowed analysis of urine samples with a wide range of concentrations and increased the sensitivity of the assay. AQP2 in the urine existed as a high molecular weight form of approximately 190 kD by HPLC analysis. The mean urinary AQP2 concentration corrected for creatinine in spot urine samples of healthy subjects who voided in the morning was 1081 +/- 699 fmol/mg creatinine (mean +/- SD, n = 208). The amount of daily excretion of AQP2 in the urine was the same in men and women. Urinary AQP2 content was not affected by age of the subjects and showed a positive correlation with urine osmolality. Finally, the fraction of AQP2 excreted in the urine compared with whole kidney content was determined in the rat. Approximately 3% of AQP2 in the kidney was excreted daily, and this fraction did not change when rats were dehydrated for 3 d. These data demonstrate the necessity of establishing well-designed protocols to use urinary AQP2 as a marker of AVP action.

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