Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody

Katherine Kelly, Shane M. Meehan, Robert B. Colvin, Winfred W. Williams, Joseph V. Bonventre

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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. Conclusion. CD54 may be critical in the pathophysiology of renal injury following cisplatin, perhaps by its effects on leukocyte-endothelial interactions.

Original languageEnglish (US)
Pages (from-to)922-931
Number of pages10
JournalKidney International
Volume56
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Cisplatin
Anti-Idiotypic Antibodies
Kidney
Wounds and Injuries
Mortality
Intercellular Adhesion Molecule-1
Peroxidase
Renal Insufficiency
Creatinine
Leukocytes
Monoclonal Antibodies
Placebos
Messenger RNA
Neoplasms

Keywords

  • Acute renal failure
  • Adhesion receptors
  • Cisplatin toxicity
  • Intercellular adhesion molecule- 1
  • Leukocyte
  • Nephrotoxicity

ASJC Scopus subject areas

  • Nephrology

Cite this

Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody. / Kelly, Katherine; Meehan, Shane M.; Colvin, Robert B.; Williams, Winfred W.; Bonventre, Joseph V.

In: Kidney International, Vol. 56, No. 3, 1999, p. 922-931.

Research output: Contribution to journalArticle

Kelly, Katherine ; Meehan, Shane M. ; Colvin, Robert B. ; Williams, Winfred W. ; Bonventre, Joseph V. / Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody. In: Kidney International. 1999 ; Vol. 56, No. 3. pp. 922-931.
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