TI - Cyclosporine A induces senescence in renal tubular epithelial cells . AB - The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A ( CsA ) is well recognized . However , the mechanism of renal tubular toxicity is not yet fully elucidated . Chronic CsA nephropathy and renal organ aging share some clinical features , such as renal fibrosis and tubular atrophy , raising the possibility that CsA may exert some of its deleterious effects via induction of a stress-induced senescent phenotype . We investigated this hypothesis in HK-2 cells and primary proximal tubular cells in vitro . CsA induced the production of H2O2 , caused cell cycle arrest in the G0/G1 phase , and inhibited DNA synthesis . Furthermore , CsA exposure lead to a reduction of telomere length , increased p53 serine 15 phosphorylation , and caused an upregulation of the cell cycle inhibitor p21 ( Kip1 ) (CDKN1A) mRNA levels . CsA caused an increase in p16 (INK4a) (CDKN2A) expression after a 13-day exposure in primary proximal tubular cells but not in HK-2 cells . Coincubation of cells with CsA and catalase was able to prevent telomere shortening and partially restored DNA synthesis . In summary , CsA induces cellular senescence in human renal tubular epithelial cells , which can be attenuated by scavenging reactive oxygen species .