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Although cyclosporine has high specificity for the immune system, immunosuppressive therapy with CsA is often complicated by nephrotoxicity. The main morphologic targets of CsA nephrotoxicity include the tubular epithelial and endothelial cells. These cells were investigated in vitro. CsA caused a dose- and time-dependent inhibition of cell growth, vacuolization and fatty change in adherent cells, detachment, and cell death. Inhibition of 3H-TdR incorporation in cells of both tubular epithelial and endothelial origin occurred between 3 microM and 10 microM. Electron microscopy studies revealed cellular swelling, dilatation of the endoplasmic reticulum, and the presence of lipid droplets and giant mitochondria. The...