Antioxidant and Oxidative Stress Indices in Dialysis-Dependent Acute Renal Failure

Abstract

Background: Experimental animal models and in vitro studies have established a role for reactive oxygen species and the therapeutic potential for free radical scavengers in acute renal failure (ARF). Little is known of the effects of hemodialysis and other clinical variables on antioxidant defenses and oxidative stress among patients with ARF. Methods: We examined antioxidant defenses and oxidative stress status in 24 patients with ARF requiring hemodialysis (HD). Blood samples were drawn prior to the first dialysis session (baseline), as well as before and after the third and sixth dialysis sessions. At each time point, the following parameters were measured: plasma α-tocopherol (vitamin E), plasma glutathione peroxidase (GSH-Px), serum total oxygen radical absorbance capacity (ORAC), plasma thiobarbituric acid reactive substances (TBARS), plasma tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). Multivariate linear regression analyses were performed to examine clinical/laboratory variables associated with antioxidant/oxidative stress indices. The changes in antioxidant/oxidative stress indices over time after initiation of hemodialysis was evaluated in a subgroup of patients (n = 11) who completed six dialysis sessions. Intradialytic changes in antioxidant/oxidative stress indices and the differential impact of cellulose acetate vs. polysulfone dialyzers were also evaluated. Results: Factors associated with α-tocopherol level were serum albumin (301 µg/dl ↑ for each 1 g/dl ↑ in albumin) and ORAC (188 µg/dl ↑ for each 1,000 µmol Trolox Eq/l ↑ in ORAC). Age was independently associated with plasma GSH-Px levels (55 U/l ⇓ for each 10-year age ↑ ). Factors associated with ORAC were α-tocopherol (85 µmol Trolox Eq/l ↑ for each 100 µg/dl ↑ in α-tocopherol) and total bilirubin (30 µmol Trolox Eq/l ⇓ for each 1 mg/dl ↑ in total bilirubin). Total bilirubin was independently associated with TBARS (0.2 µM ↑ for each 1 mg/dl ↑ in total bilirubin). GSH-Px and ORAC levels declined over time between baseline and the sixth dialysis session (p < 0.05 for both). Finally, there was a significant intradialytic decline in ORAC levels, which appeared to be more pronounced with use of cellulose acetate compared with polysulfone dialyzer membranes (p < 0.05). Conclusions: These observations indicate that antioxidant and oxidative stress indices in ARF patients are associated with several clinical and laboratory variables as well as the dialysis procedure. Further studies are needed to investigate the therapeutic role of anti-oxidant therapy in these patients.