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Acute cyclosporine A-induced nephrotoxicity: a rabbit model
A Prévot1, D S Semama, E Justrabo
1Laboratoire de Néphrologie-Hémaphérèse-Transplantation (UPRES EA 563), Centre Hospitalier Universitaire, Dijon, France.
Pediatric Nephrology (Berlin, Germany)
|May 11, 2000
Summary
Acute cyclosporine A (CsA) causes kidney injury through vasomotor dysfunction, not the vehicle. This acute nephrotoxicity is partly reversible upon CsA discontinuation.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Cyclosporine A (CsA) nephrotoxicity is well-documented, but acute effects are less understood.
- Short-term CsA use necessitates models for acute nephrotoxicity.
- This study investigates acute CsA-induced kidney injury in rabbits.
Purpose of the Study:
- To develop and characterize an experimental model of acute CsA nephrotoxicity.
- To assess the impact of CsA on renal function and hemodynamics.
- To determine the role of the vehicle (Cremophor-EL) and reversibility of effects.
Main Methods:
- 35 New Zealand rabbits were divided into control, CsA, vehicle, and follow-up groups.
- Renal clearances of inulin and para-aminohippurate were measured.
- Renal blood flow (RBF), glomerular filtration rate (GFR), renal vascular resistance (RVR), and diuresis were assessed.
Main Results:
- CsA significantly decreased GFR, RBF, and diuresis, increasing RVR.
- Proportional falls in GFR and RBF suggest pre- and postglomerular vasoconstriction.
- Microvacuolization of proximal tubule cells was the only histological finding in CsA-treated rabbits.
- Cremophor-EL alone did not significantly alter renal function, but increased RBF.
- Discontinuation of CsA led to RVR normalization and improved renal function.
Conclusions:
- Acute CsA administration induces vasomotor acute renal failure in rabbits.
- The observed nephrotoxicity is attributable to CsA, not its vehicle, Cremophor-EL.
- The acute renal effects of CsA are partly reversible after treatment cessation.