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Experimental cyclosporin A nephrotoxicity

P H Whiting, A W Thomson, J T Blair

    British Journal of Experimental Pathology
    |February 1, 1982
    PubMed
    Summary
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    Cyclosporin A (Cy A) causes kidney damage in rats, evidenced by impaired filtration and tubular injury. Doses directly correlate with the severity of nephrotoxicity and cellular damage observed.

    Area of Science:

    • Nephrology
    • Toxicology
    • Pharmacology

    Background:

    • Cyclosporin A (Cy A) is an immunosuppressant with known nephrotoxic potential.
    • Understanding the dose-dependent effects of Cy A on renal function is crucial for patient management.

    Purpose of the Study:

    • To investigate the nephrotoxic properties of Cyclosporin A (Cy A) in Sprague-Dawley rats.
    • To characterize the biochemical and structural renal damage induced by various Cy A dose regimens over 21 days.

    Main Methods:

    • Administration of varying Cyclosporin A doses to Sprague-Dawley rats over a 21-day period.
    • Assessment of glomerular filtration via serum urea and creatinine levels and urea clearance rates.
    • Measurement of urinary N-acetyl-beta-D-glucosaminidase activity.

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  • Histopathological and ultrastructural examination of renal proximal tubules.

    • Main Results:

    • Elevated serum urea and creatinine levels, alongside reduced urea clearance, indicated glomerular filtration impairment.
    • Dose-dependent increases in urinary N-acetyl-beta-D-glucosaminidase activity were observed.
    • Structural damage to proximal tubules included cytoplasmic vacuolation, endoplasmic reticulum dilatation, cell necrosis, and desquamation at higher doses.
    • Ultrastructural analysis revealed dose-related abnormalities throughout the proximal tubule, such as increased lysosomes, cytosegresomes, and myeloid bodies.

    Conclusions:

    • Cyclosporin A induces significant nephrotoxicity in rats, affecting both glomerular filtration and proximal tubular integrity.
    • The observed biochemical and structural changes demonstrate a clear dose-response relationship for Cy A-induced kidney damage.
    • These findings highlight the importance of monitoring renal function in patients treated with Cyclosporin A.