Gammaglutamyltransferase in ESRD as a predictor of all-cause and cardiovascular mortality: another facet of oxidative stress burden

The enzyme gamma-glutamyltransferase (GGT) is an established marker of liver function and alcohol consumption and represents the major factor responsible for the extra-cellular catabolism of the main antioxidant in mammalian cells, Glutathione. ESRD is a condition characterized by a high risk of death and cardiovascular (CV) complications and with a high prevalence of liver disease but the link between GGT and clinical outcomes has never been studied in this population. We tested the predictive power of GGT for overall and cardiovascular mortality in a cohort study in 584 ESRD patients. Over a 4 years follow up 194 patients died. GGT was higher in non-survivors (median 25 UI/l, interquartile range 16-45 UI/l) than in survivors (22, 15-33 UI/l) (P = 0.006). On univariate Cox regression analysis plasma GGT predicted both all-cause [HR (10 UI/l increase): 1.04, 95% CI: 1.01-1.06, P = 0.006] and cardiovascular mortality [HR: 1.03, 95% CI: 1.00-1.05, P = 0.04]. These relationships held true in multivariate Cox regression analyses [HR: 1.06, 95% CI: 1.03-1.10 (P < 0.001) and 1.05, 95% CI: 1.01-1.10, P = 0.01] adjusting for liver disease as well as Framingham risk factors and non traditional risk factors including C reactive Protein (CRP). High GGT in ESRD patients is a strong, independent risk marker for all cause and cardiovascular death. The predictive power of GGT for these outcomes likely reflects the involvement of this enzyme in oxidative stress mechanisms.