title: Administration of dexamethasone induces proteinuria of glomerular origin in mice.
abstract: The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observed that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration. One fourth of mice also intermittently presented with slight hematuria beginning on day 12. Renal lesions in the dexamethasone-treated mice, which were killed on day 23, were characterized by mild mesangial expansion, segmental or global hyalinosis/sclerosis in deep cortical glomeruli, and focal tubular changes. No glomerular inflammatory cell infiltration or proliferative lesion was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mesangial matrix, dilated mesangial channels filled with slightly electron-dense material or mesangial lysis-like appearance showing intracytoplasmic microcysts filled with electron-lucent material, and evidence to support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of IgG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the dexamethasone-treated mice. Charge analysis showed no impairment in anionic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuated by treatment with a low molecular weight heparin, although it was not reduced by an angiotensin-converting enzyme inhibitor. Data from these experiments suggest that a large dose of glucocorticoids is potentially nephrotoxic. Alteration of a size-dependent permeability may predominantly contribute to the dexamethasone-induced proteinuria. However, the effect of glomerular hyperfiltration may be only partially involved in the pathogenesis of this dexamethasone-induced glomerulopathy in mice.
authors.affiliation: Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan, ROC.
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: L F
authors.initials: LF
authors.lastname: Sheu
authors.forename: Y S
authors.initials: YS
authors.lastname: Ho
authors.forename: Y F
authors.initials: YF
authors.lastname: Lin
authors.forename: W Y
authors.initials: WY
authors.lastname: Chou
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D002216:Captopril / Q000494:pharmacology; D003176:Complement C3 / Q000032:analysis; D003404:Creatinine / Q000097:blood; D017985:Dalteparin / Q000494:pharmacology; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity*; D006417:Hematuria / Q000139:chemically induced / Q000503:physiopathology; D007136:Immunoglobulins / Q000032:analysis; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012709:Serum Albumin / Q000032:analysis; D014463:Ultrasonography
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000925:Anticoagulants; D001786:Blood Glucose; D003176:Complement C3; D005938:Glucocorticoids; D007136:Immunoglobulins; D012709:Serum Albumin; D003907:Dexamethasone; D002216:Captopril; D003404:Creatinine; D017985:Dalteparin