抄録
We compared the effectiveness of routinely used kidney markers and urinary RPA-1 in rats treated with desmopressin (dDAVP), a selective V2 agonist that influences the function of the collecting ducts. dDAVP was administered subcutaneously to rats at dose levels of 0.2, 2, 20 and 200 μg/kg for 28 days. Urinalysis and urinary RPA-1 analysis were conducted before dosing and during the dosing period (Days 1, 2, 3, 6, 14 and 27). Rats were sacrificed on Days 8 and 29, after which blood chemistry testing and histopathological examination of the kidney was conducted. Immunohistochemistry for RPA-1 was also performed. Urinary RPA-1 increased in a dose-related manner at 2 μg/kg or more from Day 6, although the presence of routinely-used renal markers increased only at the highest dose of 200 μg/kg on Day 27. At 2 μg/kg or more on Days 8 and 29, histopathological examination revealed hypertrophic and hyperplastic changes in the epithelial cells of the collecting ducts. The severity and extent of these epithelial changes were dependent on the dose level. Papillary necrosis, tubular dilatation in the cortex and tubular regeneration were also observed at 200 μg/kg. Immunohistochemically, the staining intensity of RPA-1 increased in the collecting ducts with hypertrophic/hyperplastic changes. These results demonstrated that the urinary RPA-1 level correlated well with not only cellular damage, but renal tubular changes. Therefore, urinary RPA-1 was considered to be a sensitive biomarker of the renal changes induced by vasopressin V2 receptor agonists in rats.
