Reversibility of chronic cyclosporine nephropathy in rats after withdrawal of cyclosporine.
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.
Li
Can
C
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Yang
Chul Woo
CW
Kim
Wan Young
WY
Jung
Ju Young
JY
Cha
Jung Ho
JH
Kim
Yong Soo
YS
Kim
Jin
J
Bennett
William M
WM
Bang
Byung Kee
BK
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
D007166:Immunosuppressive Agents; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D016572:Cyclosporine; D012083:Renin