臺灣博碩士論文加值系統

台灣慢性腎臟病(Chronic Kidney Disease, CKD)盛行率為11.9%，同時是全球末期腎臟病(End Stage Renal Disease, ESRD)最高盛行率的國家。過去已知性別、年齡、抽菸、肥胖、高血脂、高血壓和糖尿病是腎功能持續惡化的危險因子。近年來，許多研究對空氣污染物與慢性腎臟病或是末期腎病之間的相關性進行討論。因此，本研究目的除了探討長期暴露空氣污染物與腎功能惡化之相關性，進一步探討生化指標改變量在長期暴露空氣污染物與腎功能惡化之間是否扮演中介關係之角色。

本研究為2008年到2020年之回溯性世代研究，自台灣人體生物資料庫中，選取研究追蹤期間無搬家、兩次生化指標無遺漏值，排除腎絲球過濾率的基線值在60 mL/min/1.73m2以下，或任一次在135 mL/min/1.73m2以上受試者，共26,682名。將腎功能快速惡化定義為平均每年超過下降5mL/min/1.73m2。根據土地利用回歸克利金法加機器學習以及居住地之鄉鎮市區推估每位研究對象的細懸浮微粒(PM2.5)和二氧化氮(NO2)濃度。使用Cox比例風險模型，分析追蹤期間PM2.5和NO2平均濃度與腎功能快速惡化之間的相關性。並且用因果中介分析，評估生化指標改變量在PM2.5和NO2與腎功能快速惡化之間的中介關係。

所有研究對象年齡平均51.96 ± 9.76歲，其中有17,422(65.29%)為女性。在調整年齡、性別、抽菸習慣、婚姻狀況、地區、藥物過敏、痛風、高血脂、高血壓、糖尿病、代謝症候群、心血管疾病、中風和腎衰竭家族病史後， PM2.5和NO2每增加1μg/m3，腎功能惡化的風險顯著增加1.08 (95%CI:1.06, 1.10)和1.06 (95%CI:1.04, 1.08)倍。雙污染模型中，PM2.5和NO2每增加1μg/m3，則顯著增加1.07 (95%CI:1.05, 1.09)和1.05 (95%CI:1.03, 1.07)倍的危險性。在中介分析結果中發現，30到65歲中壯年健康男性，長期暴露PM2.5，會分別透過醣化血色素(4.10%, 95%CI : 0.13, 8.08)和尿酸(7.63%, 95%CI : 0.20, 15.07)顯著增加腎功能惡化的發生機率。

本研究結果發現，在調整危險因子後，長期暴露於PM2.5和NO2會顯著增加腎功能惡化的風險。其中，中壯年健康男性族群暴露PM2.5會分別透過醣化血色素和尿酸來增加腎功能快速惡化的風險。

The prevalence of chronic kidney disease in Taiwan is 11.9%, and Taiwan is also the country with the highest prevalence of end stage renal disease in the world. Gender, age, smoking, obesity, hyperlipidemia, hypertension and diabetes have been known to be risk factors for persistent deterioration of renal function in the past. In recent years, many studies have discussed the association between air pollutants and chronic kidney disease or end-stage renal disease. Therefore, the purpose of this study is not only to investigate the correlation between long-term exposure to air pollutants and the deterioration of renal function, but also to further explore whether the changes in biochemical indicators play a mediating role between long-term air pollutant exposure and the deterioration of renal function.

This study is a retrospective cohort study from 2008 to 2020. In the Taiwan Biobank, selected people with no moving and no missing values of two biochemical indicators. Baseline value of without the glomerular filtration rate was 60 mL/min/1.73m2 or less, or any one time above 135 mL/min/1.73m2 were excluded, a total of 26,682 subjects. Rapid deterioration in renal function was defined as a mean decline of more than 5 mL/min/1.73m2 per year. Particulate matter (PM2.5) and nitrogen dioxide (NO2) were estimated for each subject based on land-use regression /kriging method plus machine learning. Correlations between mean concentrations of PM2.5 and NO2 and rapid deterioration of renal function were analyzed using a Cox proportional hazards model. And causal mediation analysis was used to analyze the mediating relationship between the changes of biochemical indicators between PM2.5 and NO2 and the rapid deterioration of renal function.

The mean age of all study subjects was 51.96 ± 9.76 years, and 17,422 (65.29%) of them were female. After adjusting for age, gender, smoking habits, marital status, region, drug allergy, gout, hyperlipidemia, hypertension, diabetes, metabolic syndrome, cardiovascular disease, stroke, and family history of renal failure, PM2.5 and NO2 increased for each at 1 μg/m3, the risk of renal function was significantly increased by 1.08 (95%CI: 1.06, 1.10) and 1.06 (95%CI: 1.04, 1.08). In the two pollutants model, each 1 μg/m3 increase in PM2.5 and NO2 significantly increased the risk by 1.07 (95%CI: 1.05, 1.09) and 1.05 (95%CI: 1.03, 1.07) times. In the results of the mediation analysis, it was found that the long-term exposure of PM2.5 in healthy men aged 30 to 65 would pass through glycosylated hemoglobin (4.10%, 95%CI: 0.13, 8.08) and uric acid (7.63%, 95%CI: : 0.20, 15.07) significantly increased the incidence of renal function.

The results of this study found that long-term exposure to PM2.5 and NO2 significantly increased the risk of worsening renal function after adjustment for risk factors. Exposure to PM2.5 in middle-aged healthy men increases the risk of rapid deterioration of renal function through glycosylated hemoglobin and uric acid, respectively.

誌謝 I
摘要 II
Abstract III
目錄 V
表目錄 VI
圖目錄 VII
第一章 前言 1
第一節 研究背景與動機 1
第二節 研究假說 2
第三節 研究目的 2
第二章 文獻探討 3
第一節 腎功能快速惡化之研究 3
第二節 空氣污染(PM2.5和NO2)與腎功能快速惡化之研究 7
第三節 空氣污染物(PM2.5和NO2)之因果中介分析之研究 9
第三章 材料與方法 11
第一節 研究設計 11
第二節 研究對象 12
第三節 疾病定義 13
第四節 調查問卷、臨床資料及生物檢體 14
第五節 空氣污染物 15
第六節 統計分析 17
第四章 結果 18
第一節 不同程度的腎功能之基本人口學、生活習慣、共病症病史、生化指標 18
第二節 基本人口學、生活習慣、共病症病史、生化指標和空氣污染物與腎功能快速惡化之相關性 28
第三節 空氣污染物與腎功能快速惡化之間的中介關係 42
第五章 討論 53
第六章 結論 57
參考文獻 58

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