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研究生:鄭雅勻
研究生(外文):Ya-Yun Cheng
論文名稱:飲水含砷與慢性腎臟疾病之相關性研究
論文名稱(外文):The Associations between Arsenic in Drinking Water and Chronic Kidney Disease
指導教授:郭浩然郭浩然引用關係
指導教授(外文):How-Ran Guo
學位類別:博士
校院名稱:國立成功大學
系所名稱:環境醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:英文
論文頁數:70
中文關鍵詞:慢性腎臟病末期腎臟病存活分析美兆健檢資料庫全民健保資料庫地理資訊系統
外文關鍵詞:arsenicchronic kidney disease (CKD)end-stage renal disease (ESRD)survival analysisMJ Health Management InstitutionNational Health Insurance Research Database (NHIRD)geographic information systems (GIS)
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據以往政府調查研究指出,全臺有五十萬以上居民曾飲用含砷過量大於0.05ppm 的水,尤其在南部;而臺灣末期腎臟病發生率高居世界頂尖,也是南部較高。砷在泌尿系統排除過程中濃縮於腎臟,進而影響近曲小管與腎絲球體的功能。然而,有關砷暴露與慢性腎臟病的流行病學研究很少。本研究的目的在評估飲水含砷暴露較高地區與慢性腎臟病之發生及其進展至末期腎臟病的相關性。我們執行慢性腎臟病患者追蹤收案、2000年至2009年的美兆健檢資料庫全國性世代研究、全民健康保險資料庫百萬歸人檔執行1996年至2010年追蹤研究。另外使用地理資訊系統進行對飲水含砷暴露做更精密的風險估算,進一步探討飲水中砷暴露與慢性腎臟病之關係,並進行影響慢性腎臟病發展至末期腎臟病的因素之初步分析。
飲用水中的砷含量是根據台灣省政府衛生資料進行的一項全國性的普查調查評估的,其中有311個鄉鎮具有測量報告。目前研究發現過去井水砷暴露濃度50 μg/L (0.05 mg/L)當作切點:發現過去的井水砷暴露與慢性腎臟病發生率、嚴重程度與惡化快速進展指標(eGFR decline每年減少5 ml/min/1.73 m2以上),在校正干擾因子後仍具有統計上顯著相關其校正勝算比(adjusted odds ratio;AOR)為1.22, 95%信賴區間(confidence interval [CI])為1.05-1.42, p〈0.01)。
在1998年-2010年期間,從362,505位40歲以上參與者中確診了5,442名新發生ESRD患者,發現飲用水中砷含量≥50μg/ L的地區居民的風險對比值(HR)為1.14 (95%信賴區間[CI]:1.08-1.21, p〈0.001)為ESRD。 調整性別、年齡、收入和共病症後,發現校正後的HR為1.12 (95%CI:1.06-1.19, p〈0.001)。此外,共病症對砷暴露造成ESRD風險有顯著差異,對共病症少於三種以下的患者的影響更為顯著(低共病症分數校正後的HR = 1.51; 95%CI:1.22-1.86, p〈0.001)。 總之,高濃度的含砷飲用水是終末期腎病ESRD的危險因素,獨立於其他已知的危險因素。
預期本研究結果有助於了解飲水含砷暴露在我國南部末期腎臟病高發生率中的角色,並有助於對慢性腎臟病患者發展至末期腎臟病之易感性進行預測,以協助治療計畫之規劃。
Previous governmental surveys have showed that more than half a million residents in Taiwan had drunk water that contained arsenic levels higher than 0.05 ppm, particularly those residents in the southern part of Taiwan. On the other hand, the incidence of end-stage renal disease (ESRD) in Taiwan is among the highest in the world, and southern Taiwan also has higher incidence nationwild. During its urinary elimination, arsenic concentrates in the kidney and affects the function of proximal convoluted tubules and glomerulus. However, epidemiology studies on the associations between arsenic exposure and chronic kidney disease (CKD) are limited. The objectives of the proposed study are to evaluate the associations of arsenic exposure with the risks of CKD and with the development of CKD to ESRD, and to identify the genetic markers single nucleotide polymorphisms (SNP) of this process as well as other useful biomarkers. We will begin to recruit CKD patients’ fellow-up study at a teaching hospital in southwestern Taiwan, and conduct a nationwide cohort study on MJ Health Management Institution in Taiwan from 2000 to 2009. We will also analyze the longitudinal data on 1,000,000 people from 1996 to 2010, which are available from the National Health Insurance Research Database (NHIRD), to evaluate the associations between arsenic level in drinking water and the risks of CKD / ESRD. Secondly, we will apply geographic information system (GIS) to generate more precise data on arsenic exposure and assess its associations with CKD in greater details. We will perform preliminary analysis on the factors that affect the development of CKD to ESRD. The proposed project aims to identify the role of arsenic in drinking water in the high incidence of ESRD in southern Taiwan and to provide information on predicting of the susceptibility of development ESRD from CKD. The data generated by the proposed project shall help risk stratification of CKD patients and help the planning of individual treatment plans.
Arsenic levels in drinking water were assessed on the basis of a nationwide census survey conducted by the government, of which measurement reports were available for 311 townships.
Using both 50 μg/L (0.05 mg/L) as the cut-offs, we found most of the hot spots were in the southwestern coast and northeastern areas. Furthermore, we found exposure to arsenic in drinking water was associated with the incidence of CKD / ESRD and the rapid progression of CKD (eGFR decline〉5 ml/min/1.73 m2/year) in Taiwan, independent of most documented risk factors; the adjusted odds ratio (AOR) is 1.22, 95% confidence interval [C.I]=1.05-1.42, p〈0.01.
We identified 5,442 newly diagnosed ESRD from 362,505 members age≥ 40 years in 1998 during the study period (from 1998 to 2010) and found that residents of areas with arsenic levels≥ 50 µg/L in the drinking water had a hazard ratio (HR) of 1.14 (95% confidence interval [CI]: 1.08-1.21, p〈0.001) for ESRD. After adjusting for sex, age, income, and comorbidities, we found an adjusted HR of 1.12 (95% CI: 1.06-1.19, p〈0.001), which was still statistically significant. Furthermore, the effect was modified by comorbidities, with more prominent effects on patients with less than three comorbidities (adjusted HR=1.51; 95% CI: 1.22-1.86 for low comorbidity score, p〈0.001). In conclusion, a high arsenic level in drinking water was a risk factor for ESRD, independent of other documented risk factors.
中文摘要 III
Abstract IV
致謝 VI
Contents VII
Table List IX
Figure List X
Abbrevation XI
Chapter 1. Introdution 1
Section 1. Arsenic in drinking water and health effect 1
Section 2. Arsenic in drinking water and mechanism in renal function 3
Section 3. Arsenic in drinking water and epidemiology in renal disease 5
Section 4. Arsenic in groundwater and geo-variation in renal disease 6
Section 5. Significance of renal disease 9
Section 6. Objectives and Study designs 11
Chapter 2. Study design with flow chart 12
Chapter 3. Materials and Methods 13
Section 1. Assessment of arsenic exposure levels 13
Section 2. Database from MJ and study for progression of renal disease 15
Part 1. Data source and study participants 15
Part 2. Assessment of rapid progression in chronic kidney disease 15
Part 3. Statistical analyses 16
Section 3. Database from NHIRD and study for occurance of renal disease 18
Part 1. Data source and study participants 18
Part 2. Assessment of kidney disease and comorbidity 19
Part 3. Statistical analyses 20


Chapter 4. Results 22
Section 1. MJ Database and the progression of renal disease - J Hazard Mater 22
Part 1. Arsenic level in drinking water 22
Part 2. Study participants 22
Part 3. Risk factors for rapid progression of chronic kidney disease 23
Section 2. NHIRD Database and the occurance of ESRD - Sci Total Environ 32
Part 1. Arsenic level in drinking water 32
Part 2. The baseline characteristics of the study participants 32
Part 3. Risk factors for end-stage renal disease 33
Chapter 5. Disscusion 47
Section 1. MJ Database and the progression of renal disease - J Hazard Mater 47
Part 1. Effects of ingested arsenic on kidney function 47
Part 2. Risk factors for rapid progression of CKD 48
Part 3. Assessment of renal function 49
Part 4. Strengths and limitations of the study 50
Section 2. NHIRD Database and the occurance of ESRD - Sci Total Environ 52
Part 1. Effects of ingested arsenic on renal disease 52
Part 2. Risk factors and common comorbidities for renal disease 53
Part 3. The modification of comorbidities on effect of arsenic 55
Part 4. Strengths and limitations of the study 56
Chapter 6. Conculsion 60
Chapter 7. Reference 61
Appendex Publucation Information 69
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