慢性腎臟病患者同半胱胺酸與腎功能、氧化壓力及抗氧化能力之相關性

The associations of plasma homocysteine with renal function, oxidative stress and oxidant capacities in patients with chronic kidney disease.

鍾佩珊(Pei-Shan Chung)

指導教授 ： 黃怡嘉

中山醫學大學/健康管理學院/營養學系碩士班/碩士(2018年)

摘要

慢性腎臟病隨著疾病進展會導致許多不良的臨床結果，如心血管疾病、中風以及高同半胱胺酸血症 (同半胱胺酸濃度 ≥ 14 μmol/L)。當同半胱胺酸濃度增加時可能會增加同半胱胺酸氧化，導致製造過多的自由基，進而造成高氧化壓力及較低的抗氧化酵素 (穀胱甘肽過氧化酶) 活性。雖然高同半胱胺酸血症、氧化壓力的上升以及抗氧化能力下降皆個別被認為與慢性腎臟病病程進展有顯著的相關性，尚未清楚的是慢性腎臟病患者的同半胱胺酸濃度是否與腎功能、氧化壓力及抗氧化能力狀態有顯著相關性。本研究目的是比較第一期至第五期的慢性腎臟病患者其血漿同半胱胺酸、氧化壓力及抗氧化能力之差異；以及探討血漿同半胱胺酸與腎功能、氧化壓力及穀胱甘肽相關抗氧化能力指標之相關性。本研究是橫斷面設計，於臺中榮民總醫院腎臟科門診進行，共招募 142 位第一期至第五期慢性腎臟病患者。受試者的血漿同半胱胺酸濃度 ≥ 14 μmol/L 為高同半胱胺酸組，血漿同半胱胺酸濃度 < 14 μmol/L為正常同半胱胺酸組。結果顯示受試者隨著腎功能下降時則同半胱胺酸濃度顯著的上升，且同半胱胺酸濃度與腎功能指標 [肌酸酐 (β = 0.11, p < 0.001)、預估腎絲球過濾率 (β = -2.03, p < 0.001)] 呈顯著的相關性。高同半胱胺酸組與正常同半胱胺酸組的氧化壓力指標數值無顯著差異，但是高同半胱胺酸組的穀胱甘肽濃度顯著高於正常組，且穀胱甘肽過氧化酶活性顯著低於正常組。調整干擾因子後，同半胱胺酸濃度與氧化壓力指標無顯著相關性，但與穀胱甘肽過氧酶活性呈顯著的負相關 (β =-2.11 x 10⁻², p = 0.049)。慢性腎臟病患者的高血漿同半胱胺酸濃度不僅與腎功能下降顯著的相關，也與抗氧化酵素活性下降有顯著的相關性，但與氧化壓力無顯著相關性。

關鍵字

慢性腎臟病 ； 同半胱胺酸 ； 腎功能 ； 氧化壓力 ； 穀胱甘肽相關抗氧化能力

並列摘要

There are adverse clinical outcomes along with chronic kidney disease (CKD) progression, including of cardiovascular disease, stroke and hyperhomocysteinemia (homocysteine concentration ≥ 14 μmol/L). Elevated plasma homocysteine level may induce excessive production of reactive oxygen species through oxidation of homocysteine, leading to increased oxidative stress and decreased antioxidant enzyme activities (i.e., glutathione peroxidase). Hyperhomocysteinemia, increased oxidative stress, and decreased antioxidant capacities have been found to be associated with the risk of CKD. However, the associations of homocysteine with renal function, oxidative stress as well as antioxidant defense function have not been fully examined in CKD patients. Therefore, the purpose of our study was to compare the differences of plasma homocysteine, oxidative stress and antioxidant capacities among stage 1-5 CKD; and additionally examined the associations of plasma homocysteine with renal function, oxidative stress and antioxidant capacities in patients with CKD. This was a cross-sectional study. One hundred forty-two stage 1-5 CKD patients were recruited from the nephrology outpatient clinics of the Taichung Veterans General Hospital, Taichung, Taiwan. Patients had plasma homocysteine concentration ≥ 14 μmol/L were assigned to the hyperhomocysteinemia group, while patients had plasma homocysteine concentration <14 μmol/L were assigned to normo-homocysteinemia group. Results showed that decreased renal function [i.e., serum creatinine (β = 0.11, p < 0.001) and estimated glomerular filtration rate (β = -2.03, p < 0.001)] was associated with high plasma homocysteine concentration. There were no significant differences in oxidative stress indictors between two groups. However, patients with hyperhomocysteinemia had significantly higher levels of glutathione, but had significantly lower glutathione peroxidase activities compared with normmo-homocysteinemia patients. There were no significant association between levels of plasma homocysteine and oxidative stress indicators. However, plasma homocysteine level was significantly associated with glutathione peroxidase activity (β =-2.11 x 10⁻², p = 0.049) after adjusting for potential confounders. In conclusion, increased plasma homocysteine concentration were not only associated with decreased renal function, but also associated with decreased glutathione peroxidase activity in patients with CKD. However, plasma homocysteine was not associated with oxidative stress status.

並列關鍵字

chronic kidney disease ； homocysteine ； oxidative stress ； renal function ； glutathione related antioxidant capacities

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