title: Reversibility of chronic cyclosporine nephropathy in rats after withdrawal of cyclosporine.
abstract: Renal interstitial inflammation is an important factor in the pathogenesis of chronic cyclosporin A (CsA) nephropathy. We studied the expression of the chemoattractant osteopontin (OPN) and the relationship between OPN expression and tubulointerstitial injury in a rat model of chronic CsA nephropathy. Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15 mg/kg sc) for 5 wk and then withdrawing it for 5 or 10 wk. Renal function, histopathology (arteriolopathy, ED-1-positive cells, and tubulointerstitial fibrosis), renin-angiotensin system (RAS) activity, and OPN expression were observed during the follow-up period. Renal function deteriorated in CsA-treated rats, with the development of typical histopathology and activation of RAS. After CsA withdrawal, these parameters were significantly reversed (all P < 0.05). The upregulation of OPN mRNA and protein expression seen in CsA-treated rat kidneys was decreased 5 wk after CsA withdrawal and was further decreased after 10 wk. Of note, OPN mRNA expression correlated with the number of infiltrating macrophage (r = 0.651, P < 0.01) and tubulointerstitial fibrosis (r = 0.729, P < 0.01). These findings suggest that OPN expression and macrophage infiltration decrease after long-term CsA withdrawal in rats with established chronic CsA nephropathy, and this is closely associated with recovery from renal injury.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
authors.forename: Wan Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Jung
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Cha
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: William M
authors.initials: WM
authors.lastname: Bennett
authors.forename: Byung Kee
authors.initials: BK
authors.lastname: Bang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects*; D004334:Drug Administration Schedule; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D053495:Osteopontin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System; D012795:Sialoglycoproteins / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D016572:Cyclosporine; D012083:Renin