title: Urinary concentrating defect in experimental hemochromatosis.
abstract: We studied the urinary concentrating capacity in experimental hemochromatosis. Sprague-Dawley rats were randomized into iron (Fe)-loaded (injected sc with 1.2 g elemental iron/kg body weight as iron dextran) and pair-fed control groups. The urinary concentrating ability was studied after 10 months of iron loading. At basal condition, urine osmolality (Uosm) was significantly lower (P < 0.05) in the Fe-loaded rats compared with the control animals despite comparable urinary arginine-vasopressin (AVP) excretion in the two groups. Although 48-h water deprivation resulted in comparable rises in plasma concentration and urinary excretion of AVP in the two groups, maximal Uosm in the Fe-loaded animals was significantly lower than that seen in the control group (P < 0.01). Moreover, the observed urinary concentrating defect could not be corrected by pharmacological doses of exogenous AVP. There was no significant difference in renal chloride, sodium, calcium, or magnesium handling at either basal or sodium depleted states. Histologic studies showed marked iron deposition in the cortex and outer medulla accompanied by mild tubular atrophy particularly in the distal convoluted tubules. Thus, chronic experimental iron overload leads to nephrogenic diabetes insipidus marked by AVP-resistant urinary concentrating defect.
authors.affiliation: Department of Medicine, University of California, Irvine, USA.
authors.forename: X J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: N D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: D
authors.initials: D
authors.lastname: Pandian
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Mazowiecki
authors.forename: S Y
authors.initials: SY
authors.lastname: Liao
authors.forename: F
authors.initials: F
authors.lastname: Oveisi
mesh_terms: D000818:Animals; D005919:Glomerular Filtration Rate; D006432:Hemochromatosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007501:Iron / Q000378:metabolism*; D007671:Kidney Concentrating Ability / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D014667:Vasopressins; D012964:Sodium; D007501:Iron