Antioxidant Supplementation in Renal Replacement Therapy Patients: Is There Evidence?

Abstract

The disruption of balance between production of reactive oxygen species and antioxidant systems in favor of the oxidants is termed oxidative stress (OS). To counteract the damaging effects of prooxidant free radicals, all aerobic organisms have antioxidant defense mechanisms that are aimed at neutralizing the circulating oxidants and repair the resulting injuries. Antioxidants are either endogenous (the natural defense mechanisms produced by the human body) or exogenous, found in supplements and foods. OS is present at the early stages of chronic kidney disease, augments progressively with renal function deterioration, and is further exacerbated by renal replacement therapy. End-stage renal disease patients, on hemodialysis (HD) or peritoneal dialysis (PD), suffer from accelerated OS, which has been associated with increased risk for mortality and cardiovascular disease. During HD sessions, the bioincompatibility of dialyzers and dialysate trigger activation of white blood cells and formation of free radicals, while a significant loss of antioxidants is also present. In PD, the bioincompatibility of solutions, including high osmolality, elevated lactate levels, low pH, and accumulation of advanced glycation end-products trigger formation of prooxidants, while there is significant loss of vitamins in the ultrafiltrate. A number of exogenous antioxidants have been suggested to ameliorate OS in dialysis patients. Vitamins B, C, D, and E, coenzyme Q10, L-carnitine, a-lipoic acid, curcumin, green tea, flavonoids, polyphenols, omega-3 polyunsaturated fatty acids, statins, trace elements, and N-acetylcysteine have been studied as exogenous antioxidant supplements in both PD and HD patients.

Increasing the Magnesium Concentration in Various Dialysate Solutions Differentially Modulates Oxidative Stress in a Human Monocyte Cell Line

“…Moreover, Mg deficiency is involved in the development and maintenance of an elevated oxidative stress status, contributing to CVD in HD patients [11,24,36]. Therefore, the use of DFs with high Mg concentrations could prevent uremia-induced oxidative stress in HD patients [11,12]. In this study, we used an in vitro model to examine how higher concentrations (1, 1.25, and 2 mM) of Mg in different DFs (acetate, citrate, or both) would affect their induction of several oxidative stress parameters in THP-1 monocytes, under basal or uremic conditions.…”

“…and the activation of leukocytes, which trigger both inflammatory compounds and ROS production, contributing to oxidative damage of biomolecules (e.g., lipid peroxidation, DNA damage, etc.) [3,[9][10][11][12].Clinical and experimental evidence demonstrates that several factors inherent to the dialysis procedure itself, such as dialysis modality, iron administration, biocompatibility, and types of dialyzer membrane and dialysates, can play a key role promoting chronic inflammation and oxidative stress in HD patients [9][10][11][12]. Bio-incompatibility during HD induces leukocyte activation, which results in increased ROS production and release of pro-inflammatory cytokines [13,14].…”

“…Epidemiological studies have demonstrated an association between hypomagnesemia (low serum Mg concentration) and CVD-associated mortality in CKD patients [21][22][23][24]. Moreover, exacerbated oxidative-inflammatory stress has been associated with hypomagnesemia in HD patients [12,24]. Thus, it has been proposed that increasing the Mg concentration in DFs may be a useful strategy to prevent CVD associated oxidative stress in HD patients [12,21,22,[24][25][26][27][28].…”

“…Moreover, exacerbated oxidative-inflammatory stress has been associated with hypomagnesemia in HD patients [12,24]. Thus, it has been proposed that increasing the Mg concentration in DFs may be a useful strategy to prevent CVD associated oxidative stress in HD patients [12,21,22,[24][25][26][27][28]. Mg concentration in DFs is one of the significant determinants of Mg serum balance in HD patients [25].…”

“…and the activation of leukocytes, which trigger both inflammatory compounds and ROS production, contributing to oxidative damage of biomolecules (e.g., lipid peroxidation, DNA damage, etc.) [3,[9][10][11][12].…”