Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody.
BACKGROUND
The benefit of the potent chemotherapeutic agent cisplatin in treating neoplasms is limited by nephrotoxicity. We tested the hypothesis that CD54 [intercellular adhesion molecule-1 (ICAM-1)] is an important mediator in cisplatin-mediated renal failure.


METHODS
The effect of a monoclonal anti-CD54 antibody was evaluated in a rat model of cisplatin toxicity. Renal function, histopathology, renal myeloperoxidase activity, and mortality were determined in the anti-CD54 and placebo groups.


RESULTS
Renal CD54 mRNA expression was markedly increased by 24 hours after exposure to cisplatin in mice. An improvement in renal function, mortality, and histological abnormalities was evident in animals exposed to cisplatin and treated with anti-CD54 antibody (mAb). Seven days after the administration of cisplatin, the mean creatinine was 0.65+/-0.05 mg/dl in the rats that received anti-CD54 mAb and 4.76+/-1.42 in control animals (P<0.02). Mortality was lower in experimental animals (0 vs. 29% in control rats seven days following cisplatin, P<0.04). Histological evidence of cell injury was markedly attenuated (P<0.04) in the treated compared with the control rats.


CONCLUSIONS
CD54 may be critical in the pathophysiology of renal injury following cisplatin, perhaps by its effects on leukocyte-endothelial interactions.
Kelly
K J
KJ
Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio 45267-0585, USA. kellykj@email.uc.edu
Meehan
S M
SM
Colvin
R B
RB
Williams
W W
WW
Bonventre
J V
JV
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000276:immunology* / Q000293:injuries* / Q000473:pathology; D008297:Male; D051379:Mice; D009318:Natriuresis / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine; D009195:Peroxidase; D002945:Cisplatin