Combined nephrotoxic effects of cyclosporine and endotoxin

Fernando G. Cosio, Jeffrey T. Innes, Norris Stanley Nahman, John D. Mahan, Ronald M. Ferguson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

This study presents experimental evidence that cyclosporin (CsA) potentiates the nephrotoxicity of endotoxin. This study was motivated by clinical observations in 4 cyclosporine (CsA)-treated renal allograft recipients who developed severe, and sometimes irreversible, nephrotoxicity after infections. CsA or vehicle was administered intramuscularly to rabbits for 5 days, and subsequently both groups of animals received one dose of endotoxin intravenously. Compared with controls, CsA-treated animals demonstrated significantly higher elevations of blood urea nitrogen and serum creatinine 24 hr after endotoxin. By contrast, both groups of animals developed similar degrees of thrombocytopenia. Histologic evaluation of kidney tissues 24 hr after endotoxin revealed significantly greater tubular toxicity and a higher glomerular polymorphonuclear leukocyte (PMN) infiltration in CsA-treated animals. Semiquantitative scores of tubular damage correlated directly with the mean number of PMN/glomeruli in both groups of animals. Immunofluorescent microscopy of kidney tissues was negative for fibrinogen and for complement deposition in both CsA and control groups. We conclude that CsA enhances endotoxin nephrotoxicity in rabbits. This effect does not appear to be mediated by activation of coagulation factors. However, a role for PMN is suggested. CsA should be used with caution in patients with deteriorating renal function who are suspected of having severe bacterial infections.

Original languageEnglish (US)
Pages (from-to)425-428
Number of pages4
JournalTransplantation
Volume44
Issue number3
DOIs
StatePublished - Jan 1 1987

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Endotoxins
Cyclosporine
Kidney
Neutrophils
Rabbits
Blood Coagulation Factors
Blood Urea Nitrogen
Bacterial Infections
Thrombocytopenia
Fibrinogen
Allografts
Microscopy
Creatinine
Control Groups
Infection
Serum

ASJC Scopus subject areas

  • Transplantation

Cite this

Combined nephrotoxic effects of cyclosporine and endotoxin. / Cosio, Fernando G.; Innes, Jeffrey T.; Nahman, Norris Stanley; Mahan, John D.; Ferguson, Ronald M.

In: Transplantation, Vol. 44, No. 3, 01.01.1987, p. 425-428.

Research output: Contribution to journalArticle

Cosio, Fernando G. ; Innes, Jeffrey T. ; Nahman, Norris Stanley ; Mahan, John D. ; Ferguson, Ronald M. / Combined nephrotoxic effects of cyclosporine and endotoxin. In: Transplantation. 1987 ; Vol. 44, No. 3. pp. 425-428.
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