Escherichia coli bacteremia exacerbates cyclosporine-induced renal vasoconstriction.
The clinical observation that cyclosporine (CSA) nephrotoxicity is particularly severe in patients during and following bacterial infections has recently been made. Transplant recipients develop a marked deterioration of graft function following Escherichia coli bacteremia secondary to urinary tract infection. CSA causes intrarenal vasoconstriction which may account for its nephrotoxicity. We therefore undertook a study using the split hydronephrotic kidney model to investigate the direct in vivo effects of CSA and E. coli bacteremia on the renal microcirculation. Hydronephrotic kidneys in Sprague-Dawley rats were suspended in an environmentally controlled tissue bath. Interlobular arterial (ILA) and afferent (AFF) and efferent (EFF) arteriolar diameters were measured by in vivo videomicroscopy and red cell velocity by Doppler velocimetry. Topical administration of CSA to the kidney in the tissue bath caused a 23 +/- 1% constriction of the ILA and a 67 +/- 5% reduction in blood flow. AFF and EFF arterioles were also constricted by 21 +/- 3 and 16 +/- 2%, respectively. The intravenous infusion of live E. coli was also followed by decreases in ILA diameters and flow (38 +/- 4 and 68 +/- 4%) and AFF diameters (22 +/- 5%) while EFF diameters were unchanged. The infusion of E. coli following addition of CSA to the tissue bath resulted in a dramatically increased constriction of ILA (49 +/- 4%) and AFF (31 +/- 2%) vessels and almost abolished ILA flow (90 +/- 2%). We conclude that in this model, E. coli bacteremia exacerbates CSA-induced preglomerular vasoconstriction and suggests a scientific basis for the severe renal dysfunction noted in transplant recipients during bacterial infection.
Bloom
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IT
Department of Surgery, University of Louisville School of Medicine, Kentucky.
Bentley
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FR
Garrison
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RN
D000818:Animals; D016470:Bacteremia / Q000503:physiopathology*; D016572:Cyclosporine / Q000633:toxicity*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016572:Cyclosporine