Disparate effects of chronic and acute theophylline on cyclosporine A nephrotoxicity.

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Serval ID
serval:BIB_A24913D1CB8C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Disparate effects of chronic and acute theophylline on cyclosporine A nephrotoxicity.
Journal
Pediatric Nephrology
Author(s)
Prévot A., Liet J.M., Semama D.S., Justrabo E., Guignard J.P., Gouyon J.B.
ISSN
0931-041X
Publication state
Published
Issued date
2002
Peer-reviewed
Oui
Volume
17
Number
6
Pages
418-424
Language
english
Abstract
We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. As exogenous adenosine infusion mimics the haemodynamic changes that characterize acute renal failure (ARF), we wanted to know whether adenosine was a mediator in this model and whether an adenosine receptor blocker could prevent the CsA-induced ARF. Group 1 were untreated controls. Group 2 received CsA (25 mg/kg per day) for 5 days. Renal function parameters were measured, showing ARF in all animals compared to controls. Theophylline (1 mg/kg i.v. bolus) was then administered and renal function was reassessed. Theophylline significantly reduced renal vascular resistance (-8%) and increased renal blood flow (RBF) (+20%), glomerular filtration rate (GFR) (+50%), filtration fraction (+24%) and diuresis (+73%), suggesting that adenosine was involved in the CsA-induced ARF. In group 3, theophylline (30 mg/kg per day) was given concomitantly with CsA for 5 days. GFR was normalized, but theophylline did not hinder the drop in RBF seen with CsA alone in group 2. Microscopy observation of the kidneys showed that chronic theophylline administration aggravated the morphological changes induced by CsA alone. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with an adenosine-mediated afferent arteriolar constriction which cannot be prevented by concomitant theophylline administration.
Keywords
Animals, Cyclosporine/blood, Cyclosporine/poisoning, Drug Administration Schedule, Glomerular Filtration Rate, Immunosuppressive Agents/blood, Immunosuppressive Agents/poisoning, Kidney Failure, Acute/chemically induced, Kidney Failure, Acute/pathology, Male, Rabbits, Receptors, Purinergic P1/antagonists & inhibitors, Theophylline/administration & dosage, Theophylline/therapeutic use
Pubmed
Open Access
Yes
Create date
20/07/2009 14:22
Last modification date
01/10/2019 7:19
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