PREVENTION OF CYCLOSPORINE-INDUCED NEPHROTOXICITY WITH DIETARY GLYCINE

Background. The nonessential amino acid glycine has been used previous ly to prevent hypoxic and ischemic injury to kidney tissue in vitro. F urthermore, it was recently shown that glycine prevents activation of macrophages and neutrophils in vitro. Because there is some evidence t hat the immunosuppressant cyclosporine causes nephrotoxicity through a hypoxia-reoxygenation mechanism that could involve infiltration and a ctivation of macrophages and neutrophils, we hypothesized that dietary glycine could prevent this injury. Methods. Rats were fed a diet cont aining glycine (5%) or a control diet for 3 days before cyclosporine t reatment. To produce nephrotoxicity, cyclosporine (25 mg/kg daily by g avage) was administered for 28 days while animals were maintained on g lycine or control diets. Serum creatinine, urea, glomerular filtration rates, and kidney histology were evaluated in different treatment gro ups. Results. All rats gained weight; however, overall weight gain in the cyclosporine, glycine, and cyclosporine+glycine groups was signifi cantly less by about 40% compared with the control group. Diet consump tion was not statistically different between the groups. As expected, cyclosporine caused kidney damage in the rats fed control diet, reflec ted in significantly elevated serum urea and creatinine. In addition, cyclosporine treatment decreased glomerular filtration rate by nearly 70%, caused proximal tubular dilation and necrosis as well as increase d macrophage and neutrophil infiltration into the kidney. Dietary glyc ine prevented or minimized kidney damage due to cyclosporine in all pa rameters studied nearly completely. Furthermore, feeding glycine for u p to 1 month had no detrimental effect on kidney function. Conclusions . Dietary glycine is a safe and effective treatment to reduce the neph rotoxicity of cyclosporine.