This enzyme is synthesized as xanthine dehydrogenase, which can be converted to xanthine oxidase by calcium-dependant proteolysis32 or modification

of cysteine residues.33 In doing so, the enzyme loses its capacity to bind NADH by alterations in its catalytic site and, instead, transfers electrons to O2, thereby generating O2-.34 However, the role of uric acid in many conditions associated with oxidative stress is not clear and there are experimental and clinical data showing that uric acid also has a role in vivo as an anti-oxidant.35 Free radicals have extremely short half-lives, so that in most cases oxidative stress is measured by specific end-products of the process. Reactive species can be measured directly by electron paramagnetic resonance or various spin trapping methods, but these methods present some practical limitations, especially in humans. At present, they are RG7204 mw costly, and their safety and efficacy have not been proven. Oxidative stress biomarkers are available, and it is their use that has indicated a positive correlation between increasing oxidative stress with increasing stages of CKD.36 Assays for oxidative stress or anti-oxidant status and some of the popular biomarkers are shown in Table 3, which also indicates whether the end-product

can be measured in urine, serum, tissue, cell culture selleck kinase inhibitor or other biological products. Common and reliable assays for oxidative stress in CKD in humans are discussed specifically. As with most oxidative stress biomarkers, the isoprostanes detect levels of specific end-products from free radical damage. They are considered by some researchers to be the best available biomarker of lipid peroxidation

and have been investigated in the pathogenesis of CKD.36–38 Studies have focused primarily on F2-isoprostanes, which are formed by non-enzymatic peroxidation of arachidonyl lipids. Specifically, 8-isoprostane Molecular motor (8-epi-PGF2a) is measured. F2-isoprostanes are best detected using mass spectroscopy, and urine and plasma are typically used.39 One of their limitations as a biomarker of oxidative stress is that they are rapidly metabolized and, as a result, any increase in plasma isoprostane concentration may be due not only to their increased formation from lipid peroxidation, but also to a slower metabolism.40,41 Measurements of F2-isoprostanes also have relatively low reproducibility, for example, in the one healthy patient on a defined diet and exercise regimen, carried out at the same time of day on subsequent days.42 A final, important, consideration is that the F2-isoprostanes, like all end-product biomarkers, are a measure of whole-body oxidative stress rather than oxidative stress localized only to the kidney. Nevertheless, the use of isoprostanes has delivered important information on increased oxidative stress and related loss of kidney function,36 early in the progression of CKD.