Plasma glutathione peroxidase and its relationship to renal proximal tubule function

Selenium-dependent extracellular glutathione peroxidase (E-GPx) is found in plasma and other extracellular fluids. Previous studies have indicated tha t patients with chronic renal failure on dialysis have low plasma GPx activ ity. In this study, dialysis patients had approximately 40% of control plas ma GPx activity, while anephric individuals had lowest plasma GPx activitie s ranging from 2 to 22% of control. The residual plasma GPx activity in ane phric individuals could be completely precipitated by anti-E-GPx antibodies , indicating that all plasma GPx activity can be attributed to E-GPx in bot h normal and anephric individuals. Plasma GPx activity rises rapidly follow ing kidney transplantation, often reaching normal values within 10 days. Th e plasma GPx activity in some transplanted patients rises to levels higher than the normal range, followed by a return to the normal range. Since E-GP x in the kidney is primarily synthesized in the proximal tubules, we invest igated whether nephrotoxic agents known to disrupt proximal tubule function also affected plasma GPx activity. The beta-lactam antibiotic cephaloglyci n rapidly caused a decrease in plasma GPx activity in rabbits. In addition, the chemotherapeutic agent ifosfamide caused a decrease in plasma GPx acti vity in pediatric osteosarcoma patients. Fanconi syndrome associated with e ither ifosfamide therapy or valproic acid therapy also caused a decrease in plasma GPx activity. Thus plasma GPx activity is related to kidney functio n and is decreased in certain situations where nephrotoxic drugs are admini stered. Monitoring plasma GPx activity may have predictive value in evaluat ing the function of transplanted kidneys or in predicting those patients pa rticularly at risk of nephrotoxic injury associated with certain medication s. (C) 1998 Academic Press.