血液及腹膜透析患者的血漿微量元素與發炎反應、抗氧化能力以及氧化壓力的相關性

慢性腎臟病隨著病程進展，腎功能逐漸下降，尿毒素堆積於體內，最終造成不可逆的腎臟功能受損，稱之為末期腎臟病。目前用於治療末期腎臟病患者的替代療法除了腎臟移植外，以腹膜透析 (peritoneal dialysis, PD) 及血液透析 (hemodialysis, HD) 為主。患者於治療過程中受到透析膜或透析液等因素影響，相較健康人有微量元素缺乏、處於低度發炎、低抗氧化能力以及高氧化壓力狀態的風險。然而，目前對於不同透析形式及透析過程是否會造成血漿微量元素濃度的變化，進而影響患者的發炎反應、抗氧化能力以及氧化壓力的研究結果尚有爭議。因此，本研究目的是比較 PD 患者及 HD 患者於透析治療前後的血漿微量元素 [(銅 (copper, Cu)、硒 (selenium, Se)、鋅 (zinc, Zn)] 濃度、發炎反應、抗氧化能力以及氧化壓力指標的差異；並探討微量元素濃度與發炎反應、抗氧化能力以及氧化壓力指標之間的相關性。本研究為觀察性橫斷面研究，於臺中榮民總醫院腎臟科透析中心招募受試者，共60 名 PD 患者及 96 名 HD 患者及完成研究。收集所有患者的流行病學及臨床資料，並採集 PD 患者及 HD 患者於透析治療前後的血液檢體以進行生化及統計分析。結果顯示 PD 及 HD 患者在微量元素、發炎反應、抗氧化能力及氧化壓力的表現有所差異，且 HD 患者在透析後顯著比透析前有較高的血漿微量元素濃度及較低的抗氧化能力。經調整干擾因子後，PD 及 HD 患者的血漿 Cu 濃度與發炎反應及氧化壓力指標呈顯著正相關，患者在 HD 治療後的血漿 Se 濃度與氧化壓力呈顯著正相關，血漿 Zn 濃度與超氧歧化酶 (superoxide dismutase, SOD) 活性呈顯著負相關。依照血漿 Zn 濃度缺乏 (< 70 μg/dL) 或充足 (≥ 70 μg/dL) 狀態進行亞組分析後，處於 Zn 缺乏的 HD 患者相較 Zn 充足者有顯著較低的血漿 Zn 濃度以及較高的 SOD 活性，但於 PD 患者中沒有觀察到相似的差異情形。處於 Zn 缺乏狀態的 HD 患者於透析治療後顯著增加血漿 Se 及 Zn 濃度及氧化壓力並減少抗氧化能力，然而在處於 Zn 充足狀態的 HD 患者於透析治療後僅觀察到抗氧化能力顯著減少，微量元素濃度與氧化壓力的關係不顯著。本研究的結論為 PD 患者的血漿 Cu 濃度會影響發炎反應以及氧化壓力，HD 患者除了 Cu 的促發炎以及促氧化作用之外，也會透過調節血漿 Zn 濃度影響血漿 SOD 活性。此外，HD 患者若能維持充足的血漿 Zn 濃度，似乎有助於抵抗透析過程中的促氧化傷害。

關鍵字

腹膜透析；血液透析；微量元素；發炎反應；抗氧化能力；氧化壓力

並列摘要

As the progression of chronic kidney disease, kidney function gradually declines and urinary toxins accumulate in the body, eventually resulting in irreversible impairment of kidney function, called end-stage renal disease (ESRD). In addition to kidney transplantation, the renal replacement therapy used to treat ESRD patients are peritoneal dialysis (PD) and hemodialysis (HD). Patients are more likely to be at risk of trace element deficiencies, low inflammatory responses, low antioxidant capacities, and high oxidative stress compared to healthy individuals due to the effects of dialysis membranes and dialysis fluid. There are controversial findings on whether different types of dialysis and dialysis processes which may have influences on plasma trace element concentrations, which in turn may affect patients' inflammatory responses, antioxidant capacities, and oxidative stress. Therefore, the purpose of this study was to compare plasma trace element concentrations [copper (Cu), selenium (Se), and zinc (Zn)], inflammatory responses, antioxidant capacities, and oxidative stress markers between PD patients, HD patients at pre- and post-HD, and to investigate the relationship of trace element concentrations with indicators of inflammatory responses, antioxidant capacities and oxidative stress. This study was an observational cross-sectional design. Sixty PD patients and ninety-six HD patients were recruited from the renal dialysis center of Taichung Veterans General Hospital, Taichung, Taiwan. Epidemiological and clinical data were collected from all patients, and blood samples were drawn from PD patients, HD patients at pre- and post-HD for biochemical analyses. Results shows that PD and HD patients had different performances in trace elements, inflammatory response, antioxidant capacities and oxidative stress. Patients at post-HD had significantly higher plasma trace elements concentration and lower antioxidant capacities than patients at pre-HD. Plasma Cu concentration was significantly positively correlated with indicators of inflammatory response and oxidative stress in PD and patients at pre-HD after adjusting for confounding factors. In patients at post-HD, plasma Se concentration was significantly positively correlated with oxidative stress indicator, and plasma Zn concentration was negatively correlated with superoxide dismutase (SOD) activity. After subgroup analysis according to plasma Zn deficient (< 70 μg/dL) or adequate (≥ 70 μg/dL) status, HD patients with Zn deficiency had significantly lower plasma Zn concentrations and higher SOD activity compared to those patients with adequate Zn status, but the similar differences were not observed in PD patients. HD patients with Zn deficiency had reduced plasma Se and Zn concentrations, increased oxidative stress, and reduced antioxidant capacities of post-HD when compared with levels at pre-HD. HD patients with adequate Zn at pre-HD had decreased antioxidant capacities at post-HD. In conclusion, plasma Cu concentration in PD patients might affect inflammatory responses and oxidative stress. In addition to pro-inflammatory and pro-oxidative effects of Cu, plasma SOD activity might be affected by the modulation of plasma Zn concentration in HD patients. To maintain normal plasma Zn concentration in HD patients seemed to have the resistance on the pro-oxidative damage during dialysis session.