慢性腎臟病患者的硫酸吲哚酚濃度與腎功能、穀胱甘肽及其相關抗氧化酵素之關係

The associations of indoxyl sulfate with renal function and glutathione related antioxidant capacities in patients with chronic kidney disease

林佩芝(Pei-Chih Lin)

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(2020年)

https://doi.org/10.6834/csmu202000280

摘要

慢性腎臟病 (chronic kidney disease, CKD) 患者體內尿毒素的增加和抗氧化能力的下降對於 CKD 病程的進展有嚴重的影響。硫酸吲哚酚 (indoxyl sulfate, IS) 是一種源自於腸道的尿毒素，且已被證實具有促氧化的特性，可能會導致 CKD 患者的氧化壓力增加，相較於健康人承受較高的氧化壓力，使得氧化–抗氧化能力失去平衡，進而惡化腎功能。穀胱甘肽 (glutathione, GSH) 及其相關抗氧化酵素是人體重要的抗氧化防禦系統，血漿 GSH 濃度和穀胱甘肽過氧化酶 (glutathione peroxidase, GPx) 活性隨著腎臟功能逐漸衰退而下降。因此，GSH 與氧化型穀胱甘肽 (oxidized glutathione, GSSG) 的比值 (GSH/GSSG ratio) 及相關抗氧化酵素活性被認為是可用來判定 CKD 患者氧化壓力與抗氧化能力的重要指標。目前尚未清楚隨著 CKD 病程進展的血漿 IS 濃度變化與 GSH 及其相關抗氧化酵素活性的相關性，因此本研究的目的是探討 CKD 患者 IS 濃度與腎功能 [ 預估腎絲球過濾率 (estimated glomerular filtration rate, eGFR)、CKD 期別 ]、GSH 濃度及其相關抗氧化酵素活性變化之相關性。本研究是重複橫斷面試驗，於臺中榮民總醫院腎臟科門診進行，招募 121 位第一期至第五期的 CKD 患者，於第 0 個月 (基線期) 及 9 個月後 (追蹤期) 進行資料收集以及抽取空腹血液進行生化值分析。結果顯示 IS 濃度於研究期間無顯著變化。CKD 患者於追蹤期的肌酸酐 及 GSSG 濃度顯著高於基線期；但 eGFR、GSH、GPx 及 GSH/GSSG ratio 顯著低於基線期。調整干擾因子後，基線期的 IS 濃度與腎功能、GSH、GSSG 及 GPx 活性有顯著相關，但此相關性在追蹤期時消失。本研究的 CKD 患者的 IS 濃度與腎功能下降有持續的顯著相關性。有趣的是 IS 濃度與 GSH 及其相關抗氧化能力的顯著相關性在整個研究期間並無持續性，可能是因為患者體內為了應付增加的氧化壓力而顯著消耗 GSH 及 GPx 活性，使得在研究期間無顯著變化的 IS 濃度 與 GSH 及 GPx 在追蹤期呈現不顯著的相關性。

關鍵字：慢性腎臟病、硫酸吲哚酚、腎功能、穀胱甘肽、穀胱甘肽過氧化酶

關鍵字

慢性腎臟病 ； 硫酸吲哚酚 ； 腎功能 ； 穀胱甘肽 ； 穀胱甘肽過氧化酶

並列摘要

Chronic kidney disease (CKD) patients with increased uremic toxins and decreased antioxidant capacities might have significant impacts on the progression of CKD. Indoxyl sulfate (IS) is a uremic toxin derived from the intestinal tract and has been shown to have pro-oxidant properties, which might lead to increased oxidative stress and imbalance of oxidant and antioxidant, which in turn worsens kidney function in patients with CKD when compared with healthy subjects. Glutathione (GSH) and its related antioxidant enzymes are important antioxidant defense system of the human body. The plasma GSH levels and glutathione peroxidase (GPx) activity decrease as the kidney function gradually declines. Therefore, the ratio of GSH to oxidized glutathione (GSSG) (GSH/GSSG ratio) and GSH related antioxidant enzyme activities are considered important indicators that can be used to determine the oxidative stress and antioxidant capacity in CKD patients. Since the changes and inter-relationships of plasma IS concentrations, GSH and its related antioxidant enzyme activities during CKD progression are not clear, the purpose of this study was to explore the correlation of IS concentrations with the changes of, renal function [estimated glomerular filtration rate (eGFR), CKD stage], GSH concentrations and its related antioxidant enzyme activities in patients with CKD. This was a repeated cross-sectional study. One hundred twenty-one patients of CKD stage 1 to stage 5 were recruited from the nephrology outpatient clinics of the Taichung Veterans General Hospital, Taichung, Taiwan. Data were collected and fasting blood samples were drawn for biochemical analysis at month 0 (baseline) and 9 months later (follow-up). The results of this study showed that the IS concentrations did not change significantly during the study. The creatinine and GSSG concentrations of CKD patients during the follow-up were significantly higher than the baseline levels; however, the levels of eGFR, GSH, GPx, and GSH/GSSG ratio were significantly lower than the baseline levels did. After adjusting for confounding factors, the IS concentration at baseline had a significant correlation with renal function, GSH, GSSG, and GPx activity; however, this correlation disappeared at the follow-up. The IS concentration of our CKD patients had a consistent and significant correlation with decreased renal function during study period. Interesting finding was that the significant correlation of GSH and its related antioxidant capacity had no consistent correlation, our CKD patients exhausted their GSH and GPx to cope with the increased oxidative stress which lead to unchanged IS concentration lost its significant correlation with GSH and GPx at the follow-up.

Key words: chronic kidney disease, indoxyl sulfate, renal function, glutathione, glutathione peroxidase

並列關鍵字

chronic kidney disease ； indoxyl sulfate ； renal function ； glutathione ； glutathione peroxidase

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