title: Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice.
abstract: Hydronephrosis is a commonly found disease state characterized by the dilation of renal calices and pelvis, resulting in the loss of kidney function in the severest cases. A generally accepted etiology of hydronephrosis involves the obstruction of urine flow along the urinary tract. In the recent years, we have developed a mouse model of hydronephrosis induced by lactational exposure to dioxin and demonstrated a lack of anatomical obstruction in this model. We also showed that prostaglandin E2synthesis system plays a critical role in the onset of hydronephrosis. In the present study, we found that neonatal hydronephrosis was not likely to be associated with functional obstruction (impaired peristalsis) but was found to be associated with polyuria and low urine osmolality with the downregulation of proteins involved in the urine concentrating process. The administration of an antidiuretic hormone analog to the dioxin-exposed pups not only suppressed the increased urine output but also decreased the incidence and severity of hydronephrosis. In contrast to the case in pups, administration of dioxin to adult mice failed to induce polyuria and upregulation of prostaglandin E2synthesis system, and the adult mice were resistant to develop hydronephrosis. These findings suggest the possibility that polyuria could induce hydronephrosis in the absence of anatomical or functional obstruction of the ureter. It is concluded that the present animal model provides a unique example of polyuria-associated type of hydronephrosis, suggesting a need to redefine this disease state.
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yoshioka
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nishimura
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Akagi
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Fujisawa
authors.affiliation: Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanagisawa
authors.affiliation: Department of Environmental Toxicology and Center for Environmental Health Sciences, University of California, Davis, California; and.
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsumura
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan tohyamac-tky@umin.org.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006869:Hydronephrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D007774:Lactation; D008297:Male; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins; D011141:Polyuria / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D014551:Urinary Tract / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D015232:Dinoprostone
keywords: hydronephrosis; nephrotoxicity; obstructive nephropathy; water channels