Oxidative stress has emerged as a constant feature of chronic renal failure (CRF).
The presence of oxidative stress in CRF is evidenced by an overabundance of lipid,
carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients
and animals. We recently have shown that oxidative stress in CRF animals is associated
with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine
dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase
(SOD). The functional significance of these findings was confirmed by favorable response
to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative
stress in CRF plays an important role in the pathogenesis of the associated hypertension
(oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease
(oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain
proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation
(nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The
CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension,
and autoimmune diseases, which independently increase production of reactive oxygen
intermediates, and frequently are associated with CRF. In addition, dialysis treatment
(blood interaction with dialyzer membrane and dialysate impurities), acute and chronic
infections (blood access infection, hepatitis, and so forth), and excessive parenteral
iron administration intensify CRF-associated oxidative stress and its adverse consequences
in patients with end-stage renal disease. The problem is compounded by limited intake
of fresh fruits and vegetables (K(+) restriction), which contain numerous natural
phytochemicals and antioxidant vitamins.