Rotein excretion [31]. In the United Kingdom Prospective Diabetes Study, in which patients were followed-up from the diagnosis of type 2 diabetes, racial heritage was found to be an independent determinant of renal dysfunction [32]. And, recently, it has been reported that inflammatory stress, has a stronger relationship than albuminuria with early CKD in patients with diabetes of African heritage, compared with other heritage groups [33]. A large experimental evidence base supports the role of inflammatory and oxidative stress in the development of kidney lesions in diabetes. However, clinical data concerning the effect of antioxidant therapy in preventing renal (and vascular disease) is conflicting. Several studies suggest that vitamin E in non-diabetic patients with high levels of oxidative stress has a beneficial impact on hypertension-purchase TAPI-2 related disorders and reduces biochemical markers of oxidation [34, 35]. However, post hoc analyses of some antioxidant trials did not show any effect on cardiovascular or renal end-points [36, 37]. It is possible that prevalent, systemic vascular damage might mitigate any benefit of antioxidant treatment. Furthermore, these analyses have not related clinical outcomes to actual measures of vitamin E or other evaluations of oxidant and/or antioxidant status. There is some evidence that vitamin E suppresses albuminuria in patients with diabetes, preserved renal function and without cardiovascular disease PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27385778 [38]. Moreover, patients with high oxidant stress due to genetically determined low levels of the antioxidant haptoglobin, who received vitamin E, had a significantly reduced incidence of vascular events compared to controls [39]. In a rodent model of type 2 diabetes, treatment with tocotrienol-rich fractions improved glycemic status, serum lipid profile and renal function in association with restoration of antioxidant enzyme activity [40]. These data suggest that, oxidative stress promotes renal and vascular damage that may be ameliorated by an antioxidant intervention in those patients at highest risk of their development.Earle et al. J Transl Med (2016) 14:Page 6 ofPreviously, we found GPx activity to be lower in patients with type 2 diabetes of African heritage compared with Caucasians. Others have shown that low GPx activity is associated with an accelerated development of vascular lesions in both experimental rodent models, and patients with diabetes [41, [42]. However, data are limited on the role of GPx activity or its regulation with respect to the development or progression of renal disease in patients with diabetes. The PREVENT trial will provide new information on whether progression of the early stages of CKD, is related to, or modified by, oxidative stress and/or host antioxidant defense mechanisms in type 2 diabetes.Funding This research is supported by a grant from Dialysis Clinic Inc (C-3305) and the National Institutes of Health Research (UKCRN ID: 8432). The funding body has provided critical scientific review in the decisions to award their Grant but has not had any role in the original design and writing of this manuscript. Received: 27 February 2016 Accepted: 11 JulyConclusions In animal models of diabetes, there is overwhelming experimental evidence for a role of oxidative stress in renal pathophysiology. However, most clinical reports of antioxidant therapy have been post hoc analyses of surrogate markers, in non-specific populations with conflicting outcomes and safety concerns.