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Nephrology pp 522-533 | Cite as

Cellular Mechanisms of Cyclosporin Nephrotoxicity

  • Robert James Walker

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.

Keywords

Mesangial Cell Renal Tubular Epithelial Cell Mixed Function Oxidase Glomerular Mesangial Cell PGE2 Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Japan 1991

Authors and Affiliations

  • Robert James Walker
    • 1
  1. 1.Department of MedicineOtago University Medical SchoolDunedinNew Zealand

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