Erythrocyte glutathione transferase: a new biomarker in chronic kidney diseases which correlates with plasma homocysteine

Abstract Homocystein (Hcy) is an important cardiovascular risk factor and it is present at high concentrations in more than 90% uremic patients. Glutathione transferases (GSTs) are a superfamily of enzymes involved in cell detoxification. Previous studies reported an increased expression of erythrocyte glutathione transferase (e-GST) in end-stage renal disease patients on maintenance hemodialysis (MHD). We re-evaluated the e-GST levels in 62 MHD patients, 50 controls and studied the correlation between this enzyme and the plasma homocysteine (Hcy). A new automated procedure for GST activity, validated by intra-assay and inter-assay measurements and by recovery experiments, showed a significant increase of e-GST activity. No correlation has been found between e-GST activity and hemoglobin, transferrin, sideremia and markers of systemic inflammation. For the first time a significant correlation was observed between increased plasma Hcy levels and e-GST activity (P < 0.0001) in MHD patients (Tab 1). The correlation between the increased level of e-GST and plasmatic Hcy concentration in MHD patients is of particular interest: plasma hyperhomocysteinemia in fact, is considered a cardiovascular risk factor and it is often associated to renal failure (van Guldener 2006). The autoxidation of this sulfur-containing amino acid produces hydrogen peroxide and high levels of Hcy reduces the bioavailability of nitric oxide forming S-nitrosohomocysteine and inhibiting NOS. Increased levels of e-GST are certainly the effect (and not the cause) of an increased cell toxicity. Thus, the correlation found in the present study between hyperhomocysteinemia and e-GST indicates that high levels of Hcy may be merely a consequence of high levels of circulating toxins. Whatever the primary cause(s) of increased levels of e-GST and Hcy in MHD patients, the present findings suggest that e-GST could be a good marker for toxin exposition and its determination may fulfill a useful probe to assess the efficiency of dialytic procedures in MHD patients. The e-GST activity could be a new biomarker useful to substitute or to be complementary to the time consuming and expensive Hcy determination in MHD patients.