Combined nephrotoxic effects of cyclosporine and endotoxin.

Abstract:

:This study presents experimental evidence that cyclosporine (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.

journal_name

Transplantation

journal_title

Transplantation

authors

Cosio FG,Innes JT,Nahman NS Jr,Mahan JD,Ferguson RM

doi

10.1097/00007890-198709000-00020

subject

Has Abstract

pub_date

1987-09-01 00:00:00

pages

425-8

issue

3

eissn

0041-1337

issn

1534-6080

journal_volume

44

pub_type

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