敗血性重症病人的血漿微量營養素、氧化壓力與抗氧化能力對腎臟預後的影響

重症病人處在敗血症狀態時為對抗體內的高度發炎及高氧化壓力，不僅容易出現血漿微量營養素、氧化壓力及抗氧化能力的失調，且因在敗血症狀態下容易併發急性腎損傷 (acute kidney injury, AKI)，導致較高的死亡率，即使存活也較容易在日後衍生慢性腎臟疾病的發生。然而過去對於敗血性重症病人的微量營養素、氧化壓力及抗氧化能力在敗血症期間的變化的研究結果並不一致，且鮮少研究將腎功能做為預後指標進行探討。因此本研究目的是比較敗血性重症病人在不同腎臟預後之間以及相同腎臟預後在轉入重症病房的第 1 天及第 7 天或轉出當天之間的微量營養素 [鋅、銅、硒 (selenium, Se)]、氧化壓力及抗氧化能力的差異；並探討病人的微量營養素、氧化壓力及抗氧化能力狀態對腎臟預後的影響。　　本研究為前瞻性橫斷面研究。於臺中榮民總醫院第一加護病房進行招募，在病人進入加護病房的第一天 (day 1) 及第七天或轉出當天 (day 7) 蒐集臨床資料及採集血液檢體以進行分析，並使用第 28 天是否發生主要腎臟不良事件 (major adverse kidney events, MAKE) 做為本研究主要臨床結果，將病人分為 non-MAKE 28 (n = 68) 及 MAKE 28 (n = 32) 組。結果顯示 MAKE28 組在 day 1及 day 7 的血漿及 day 1 的紅血球還原型穀胱甘肽 (reduced glutathione, GSH) 濃度顯著高於 non-MAKE28 組。Non-MAKE 28組在 day 7相較 day 1 有較低的紅血球 GSH 濃度。MAKE 28 組相較 non-MAKE 28 組有顯著低的血漿 Se 濃度及穀胱甘肽過氧化酵素 (glutathione peroxidase, GPx) 活性。經羅吉斯回歸調整性別、疾病嚴重度 (acute physiology and chronic health evaluation II) 及 day 1 時的 AKI 期別後，顯示 day 1 (OR, 1.002, 95% 信賴區間, 1.000 - 1.003)及 day 7 (OR, 1.003, 95% 信賴區間, 1.001 – 1.005) 的血漿 GSH 以及 day 1 (OR, 1.017, 95% 信賴區間, 1.001 – 1.033) 的紅血球 GSH 濃度較高時會增加 MAKE 28 的勝算比。較低的 day 1 血漿 GPx 活性 (OR, 0.985, 95% 信賴區間, 0.974 – 0.996) 及較低的 day 7 血漿 Se 含量 (OR, 0.802, 95% 信賴區間, 0.656 – 0.982) 也會增加 MAKE 28 的發生。此外，我們也觀察到無論是在 day 1 還是 day 7 時的血漿 Se 濃度與血漿 GPx 活性呈顯著正相關，且血漿 Se 濃度在 day 7 時與血漿 GSH 濃度呈顯著負相關。敗血性重症病人入加護病房第 1 天的血漿及血球 GSH 濃度皆可以直接預測 MAKE 28 的發生。第 1 天的血漿 GPx 活性以及第 7 天的血漿 Se 濃度可能是透過影響 GSH 濃度而間接影響 MAKE 28 的發生。若能夠確認使用敗血性重症病人轉入重症病房第 1 天的血漿 GSH 濃度做為預測病人第 28 天的腎功能預後，或許有助於降低日後慢性腎臟病的發生。

When critically ill patients are in a septic state, to combat the high levels of inflammation and oxidative stress in the body, they not only easily experience imbalances in plasma micronutrients, oxidative stress, and antioxidant capacity, but also have a higher likelihood of developing acute kidney injury (AKI) in the septic state, leading to higher mortality rates. Even if they survive, they are more likely to develop chronic kidney disease in the future. However, past research on the changes in micronutrients, oxidative stress, and antioxidant capacity in critically ill patients undergoing a septic state has been inconsistent, and few studies have explored renal function as a primary outcome. Therefore, the purpose of this study was to compare the differences in micronutrients [zinc, copper, selenium (Se)], oxidative stress, and antioxidant capacity between septic critically ill patients with different renal prognoses, as well as between the 1st day and the 7th day after admission to the intensive care unit (ICU) for the same renal prognosis. Additionally, we explored the impact of the patients' micronutrients, oxidative stress, and antioxidant capacity status on renal prognosis.This study was a prospective cross-sectional study. Recruitment was conducted in the first ICU of Taichung Veterans General Hospital. Clinical data and blood samples were collected on the 1st day (day 1) and the 7th day or the day of discharge (day 7) after patients were admitted to the ICU for analysis. The primary clinical outcome of this study was whether major adverse kidney events occurred on day 28 (MAKE 28). Patients were divided into non-MAKE 28 (n = 68) and MAKE 28 (n = 32) groups. The results showed that the plasma and erythrocyte reduced glutathione (GSH) concentrations on day 1, and plasma GSH concentrations on day 7 in the MAKE 28 group were significantly higher than those in the non-MAKE 28 group. The non-MAKE 28 group had lower erythrocyte GSH concentrations on day 7 than on day 1. The MAKE 28 group had significantly lower plasma Se concentrations and glutathione peroxidase (GPx) activity compared to the non-MAKE 28 group. Logistic regression analysis, adjusting for gender, disease severity (acute physiology and chronic health evaluation II), and the stage of AKI on day 1, showed that higher plasma GSH concentrations on day 1 (OR, 1.002, 95% CI, 1.000 – 1.003) and day 7 (OR, 1.003, 95% CI, 1.001 – 1.005), as well as higher erythrocyte GSH concentrations on day 1 (OR, 1.017, 95% CI, 1.001 – 1.033) increased the odds of MAKE 28. Lower plasma GPx activity (OR, 0.985, 95% CI, 0.974 – 0.996) at day 1 and lower plasma Se concentrations at day 7 (OR, 0.802, 95% CI, 0.656 – 0.982) also increased the incidence of MAKE 28. Additionally, we observed a significant positive correlation between plasma Se concentrations and plasma GPx activity on both day 1 and day 7, and a significant negative correlation between plasma Se concentrations and plasma GSH concentrations on day 7. The plasma and erythrocyte GSH concentrations on the 1st day of admission to the ICU in septic critically ill patients can directly predict the occurrence of MAKE 28. The plasma GPx activity on day 1 and the plasma Se concentrations on day 7 may indirectly affect the occurrence of MAKE 28 by influencing GSH concentrations. Confirming the use of plasma GSH concentrations on the 1st day of admission to the ICU in septic critically ill patients as a predictor of renal prognosis on day 28 may help reduce the incidence of chronic kidney disease in the future.