Serum gamma-glutamyltransferase levels are inversely related to endothelial function in chronic kidney disease

Gamma-glutamyltransferase (GGT) is an enzyme responsible for the extracellular catabolism of the antioxidant glutathione and recently implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is a prodromal feature of atherogenesis. Since oxidative stress is highly present in uremia and causally linked to endothelial dysfunction, we hypothesized that GGT may be a factor implicated in this process.

Serum GGT and C-reactive protein (CRP) levels, estimated glomerular filtration rate (eGFR), and 24-h proteinuria were measured in 214 nondiabetic stages 3-5 CKD patients. The endothelium-dependent vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasound. We investigated the relationship between FMD and circulating serum GGT.

Serum GGT levels were negatively associated with FMD (r = -0.41, p < 0.001) and eGFR (r = -0.34, p < 0.001) in univariate analysis. Multivariate regression analysis showed that the association between GGT and FMD persisted after adjustment for age, sex, smoking, renal function (eGFR), inflammation (CRP), proteinuria, and homeostatic model assessment index.

Circulating GGT levels significantly associate with endothelial dysfunction, an important early feature of the atherogenic process. GGT might be an early marker of oxidative or other cellular stress that it is possibly directly related to the pathogenesis of endothelial dysfunction.