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Nephrology pp 522–533Cite as

Cellular Mechanisms of Cyclosporin Nephrotoxicity

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Summary

Cyclosporin A (CsA) is a neutral lipophilic cyclic undecapeptide used extensively in transplantation. Cyclosporin A accumulates rapidly in renal tubular segments due to a partitioning process of the drug into the lipid components of the cellular membranes. Cyclosporin has been shown to inhibit protein kinase C and peptidyl-propyl cis-trans isomerase (identical to cyclophilin, an intracellular CsAbinding protein), as well as other intracellular enzymes. Inhibition of these intracellular regulatory enzymes, along with inhibition of intracellular Ca2+ flux, will significantly alter renal cellular function, including contractile activity, DNA and protein synthesis, and synthesis of prostaglandins. Inhibition of renal metabolic enzymes and alterations in renal glutathione content, in a hypoxic milieu, would enhance the toxic effects of cyclosporin.

Cellular toxicity probably has a multifactorial etiology which is related to alterations in renal vascular cells, modifying renal hemodynamics, and the relative ischemia induced by vasoconstriction potentiating sublethal changes in renal tubular epithelial cells. Histological evidence of cell damage will be apparent only if the toxic injury exceeds the capacity of the cellular mechanisms to respond to the toxic insult.

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Authors and Affiliations

  1. Department of Medicine, Otago University Medical School, PO Box 913, Dunedin, New Zealand

    Robert James Walker

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  1. Robert James Walker
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Editors and Affiliations

  1. Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

    Michinobu Hatano M.D. (Professor of Medicine, Director) (Professor of Medicine, Director)

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© 1991 Springer Japan

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Walker, R.J. (1991). Cellular Mechanisms of Cyclosporin Nephrotoxicity. In: Hatano, M. (eds) Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-35158-1_49

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  • DOI: https://doi.org/10.1007/978-3-662-35158-1_49

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-70074-6

  • Online ISBN: 978-3-662-35158-1

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