Increased intracellular reactive oxygen species in patients with end-stagerenal failure: Effect of hemodialysis

Background Reactive oxygen species (ROS) have been implicated in various fo rms of cellular injury. ROS may cause cell damage and are involved in the p athophysiology of several diseases, including atherosclerosis and chronic i nflammation. Methods. Disturbances of intracellular ROS levels were investigated in 28 p atients with end-stage renal failure. The intracellular ROS levels were mea sured in lymphocytes before and after hemodialysis using biocompatible memb ranes and were compared with those from 11 patients with end-stage renal fa ilure, not yet on renal replacement therapy, and 27 healthy control subject s. ROS levels were measured spectrophotometrically using the intracellular dye dichlorofluorescin diacetate. Results. The spontaneous production of ROS was significantly higher in lymp hocytes from patients with end-stage renal failure compared with healthy co ntrol subjects (P < 0.01). The addition of 100 nmol/L phorbol-myristate-ace tate (PMA) produced a significant increase of ROS, both in lymphocytes from patients with end-stage renal failure and healthy control subjects. The PM A-induced ROS increase was significantly higher in lymphocytes from patient s with end-stage renal failure compared with healthy control subjects (P ( 0.01). In patients with end-stage renal failure, not yet on renal replaceme nt therapy, the PMA-induced ROS was also significantly higher compared with healthy control subjects. The PMA-induced ROS increases were significantly inhibited by catalase, but not by superoxide dismutase or the superoxide d ismutase mimetic, tempol. PMA-induced ROS was significantly reduced by tyrp hostin A51 in lymphocytes from patients with end-stage renal failure and fr om healthy control subjects teach P < 0.01), indicating the involvement of a tyrosine kinase-dependent pathway. In patients with end-stage renal failu re, the spontaneous and the PMA induced production of ROS was not significa ntly different before and after hemodialysis. Conclusions. Regular hemodialysis sessions using biocompatible membranes ha ve no effect on the elevated intracellular ROS in patients with end-stage r enal failure.