Lithium chloride induces apoptosis in the porcine PK(15) renal tubular cell line

Patients receiving Li for psychiatric disorders sometimes experience altera tions in kidney function. Although controversial, some anecdotal reports in dicate a decline in renal function for a subset of patients on long-term Li therapy. While this is not a general finding in patients on Li therapy, wh ether such reports are due to unique direct effects of Li on kidney cell fu nction or other unrelated factors in this undefined subset is unclear. To e valuate potential direct effects of Li on kidney cells, the present study w as undertaken to investigate the influence of LiCl on a porcine renal tubul ar epithelial cell line [PK(15)]. Cells were treated with LiCl concentratio ns of 5-20 mM for varying time intervals. Immunocytochemistry showed that p roteins known to be elevated during apoptosis were increased following expo sure to LiCl. Furthermore, scanning and transmission electron micrographs s howed distinct apoptotic characteristics after 30 h of 20 mM LiCl treatment . These observations were substantiated by TUNEL assay analysis indicating enhanced DNA fragmentation following exposure to lithium. Thus, exposure to LiCl can induce apoptosis in cells of renal origin. While the concentratio ns of Li used in this ii vitro study are in excess of doses prescribed for psychiatric disorders, the findings do raise the possibility that some loss of cells due to apoptotic mechanisms could occur at a slow rate in the kid neys of uniquely susceptible patients maintained on Li for long periods of time.