Nephrol Dial Transplant (2000) 15: 1155-1161
© 2000 European Renal Association-European Dialysis and Transplant Association
Dissociation between urine osmolality and urinary excretion of aquaporin-2 in healthy volunteers
1 Departments of Internal Medicine, 2 Cell Physiology, and 3 Nephrology, University of Nijmegen, The Netherlands
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 µg 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/µmol 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/µmol 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.
Keywords: aquaporin-2; osmolality; urinary excretion; vasopressin; volunteers
Correspondence and offprint requests to: R. Baumgarten, University of Nijmegen, 162, Department of Cell Physiology, Trigon Building, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands.
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