Dissociation between urine osmolality and urinary excretion of aquaporin-2 in healthy volunteers.
BACKGROUND
It has been suggested that urinary excretion of the vasopressin-dependent water channel of the kidney collecting duct, aquaporin-2 (AQP2), reflects renal vasopressin action and might be used clinically. It is unclear, however, what relation exists between urine osmolality and urinary excretion of AQP2 (UAQP2) and it is unknown whether UAQP2 is influenced by hyperosmolality of urine or tubular flow rates.


METHODS
We measured urine osmolality and UAQP2 in healthy volunteers in various conditions: (i) overnight dehydration continued during the day, (ii) after infusion of 700 ml hypertonic saline (NaCl 2.5%), and (iii) after intranasal administration of 40 microg 1-desamino-8-D-arginine vasopressin (DDAVP). The last two tests were performed after water loading. In addition, a DDAVP test was performed, after administration of frusemide.


RESULTS
After overnight dehydration, the urine osmolality increased from 888+/-18 to 1004+/-17 mosmol/kg during additional hours of thirsting, whereas UAQP2 doubled from 140+/-45 to 285+/-63 fmol AQP2/micromol creatinine. Infusion of hypertonic saline increased urine osmolality from 70+/-3 to 451+/-68 mosmol/kg, while UAQP2 remained almost zero. Urine osmolality increased from 101+/-17 to 860+/-30 mosmol/kg after administration of DDAVP, with a parallel increase in UAQP2 from 32+/-14 to 394+/-81 fmol AQP2/micromol creatinine. Pre-treatment with frusemide attenuated the increase in urine osmolality, but had no effect on UAQP2 after DDAVP.


CONCLUSIONS
Our data demonstrate that a simple relationship between urine osmolality and UAQP2 does not exist. Therefore, random or once-only measurements of UAQP2 as an index of renal vasopressin action are not useful. In contrast, intranasal application of DDAVP resulted in a parallel rise in urine osmolality and UAQP2. Therefore this test might be useful in studying patients with urine concentration defects. The DDAVP-frusemide test revealed that the release of AQP2 into urine is not caused by hypertonicity of tubular fluid.
Baumgarten
R
R
Departments of Internal Medicine, Cell Physiology, University of Nijmegen, The Netherlands.
van de Pol
M H
MH
Deen
P M
PM
van Os
C H
CH
Wetzels
J F
JF
D000328:Adult; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000652:urine*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D003681:Dehydration / Q000652:urine; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D012016:Reference Values; D012076:Renal Agents / Q000494:pharmacology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D014556:Urine / Q000737:chemistry
C496023:AQP2 protein, human; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D004232:Diuretics; D012076:Renal Agents; D012462:Saline Solution, Hypertonic; D005665:Furosemide; D003894:Deamino Arginine Vasopressin