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Hemodialysis raises oxidative stress through carbon-centered radicals despite improved biocompatibility.

ABSTRACT: Leukocyte activation and the resulting oxidative stress induced by bioincompatible materials during hemodialysis impact the prognosis of patients. Despite multiple advances in hemodialysis dialyzers, the prognosis of hemodialysis patients with complications deeply related to oxidative stress, such as diabetes mellitus, remains poor. Thus, we re-evaluated the effects of hemodialysis on multiple reactive oxygen species using electron spin resonance-based methods for further improvement of biocompatibility in hemodialysis. We enrolled 31 patients in a stable condition undergoing hemodialysis using high-flux polysulfone dialyzers. The effects of hemodialysis on reactive oxygen species were evaluated by two methods: MULTIS, which evaluates serum scavenging activities against multiple hydrophilic reactive oxygen species, and i-STrap, which detects lipophilic carbon-center radicals. Similar to previous studies, we found that serum hydroxyl radical scavenging activity significantly improved after hemodialysis. Unlike previous studies, we discovered that scavenging activity against alkoxyl radical was significantly reduced after hemodialysis. Moreover, patients with diabetes mellitus showed a decrease in serum scavenging activity against alkyl peroxyl radicals and an increase in lipophilic carbon-center radicals after hemodialysis. These results suggest that despite extensive improvements in dialyzer membranes, the forms of reactive oxygen species that can be eliminated during dialysis are limited, and multiple reactive oxygen species still remain at increased levels during hemodialysis.

SUBMITTER: Hirayama A

PROVIDER: S-EPMC8325767 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Randomized trials in adults have shown reduced all-cause and cardiovascular mortality on hemodiafiltration (HDF) compared to high-flux hemodialysis (HD), but the mechanisms leading to improved outcomes are not clear. We studied biomarkers of inflammation, oxidative stress, anti-oxidant capacity and endothelial dysfunction in 22 children (13 female, age 8-15 years). All children received HD for at least 3 months, and were then switched to HDF, keeping all dialysis related parameters and dialysis time constant. All the biomarkers of inflammation (ß2-microglobulin, IL-6, IL-10, high sensitive C-reactive protein [hsCRP]), oxidative stress (nitrotyrosine, advanced glycation end-products [AGEs], oxidized low density lipoprotein [ox-LDL] and anti-oxidant capacity) and endothelial dysfunction (asymmetric dimethyl arginine [ADMA], symmetric dimethyl arginine [SDMA]), were comparable between incident and prevalent patients on HD, suggesting that even a short dialysis vintage of 3 months on HD increases inflammation and endothelial stress. After 3 months of HDF therapy there was a significant reduction in ß2-microglobulin (p<0.001), hCRP, ADMA, SDMA, AGEs, ox-LDL (p<0.01 for all) and an increase in total antioxidant capacity (p<0.001) compared to HD. All children were maintained on the same dialyser, dialysis water quality, dialysis time and blood flow speeds suggesting that improved clearances on HDF led to an improved biomarker profile. Even in children with residual renal function there was a significant reduction in ß2 microglobulin, hsCRP, SDMA, ox-LDL and AGEs on HDF compared to HD. Children with a lower blood flow had higher inflammatory status (higher IL-6/IL-10 ratio; p = 0.04, r = -0.43). Children who achieved a higher convective volume (?median 12.8L/m2) had lower ox-LDL (p = 0.02). In conclusion, we have shown that a significant improvement in inflammation, antioxidant capacity and endothelial risk profile is achieved even within a short time (3 months) on HDF compared to HD treatment. TRIAL REGISTRATION:ClinicalTrials.gov: NCT02063776.

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Hemodialysis raises oxidative stress through carbon-centered radicals despite improved biocompatibility.

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