研究背景及目的
在1910年代早期和1940年代晚期，台灣西南沿海及東北部地區的居民透過使用含高砷的自流井水而有長期砷暴露的情形，如今，雖然利用地表水的公共供水系統已在這些流行地區普遍使用，但當地居民可能仍遭受著飲水砷暴露所導致的慢性健康效應影響，如皮膚癌、膀胱癌、腎臟癌、高血壓、糖尿病和腎臟損害 (特別是腎小球及腎小管間質損害)，其可能近而進展成慢性腎臟病 (CKD)，因此，我們在CKD盛行率居高不下的台灣，執行了一個以族群為基礎的全國性的研究，來探討可能的相關性以及共病症的修飾效應。

材料與方法
本研究針對全台地區以及台灣西南地區執行了一個回溯性世代追蹤研究。使用台灣健康保險資料庫，建立了在1998年1月1日年齡大於40歲的研究世代，並確定了在1998年1月1日到2014年12月31日新發的CKD個案。飲用水之砷暴露評估是利用1974至1976年政府所執行的台灣全省311個鄉鎮水井調查地下水砷濃度的環境監測數據作為依據。而不同砷暴露程度間，發生CKD之風險比值 (HRs) 則使用Cox比例風險回歸來計算得出，同時校正潛在之干擾因子，此外，也執行了Kaplan–Meier存活曲線及Log–Rank檢定來評估砷暴露組間CKD累積未患病機率的差異，以及執行分層分析來評估共病症的修飾效應作用。

結果
全台地區6,573,192位參與者的研究世代中，在研究期間共有1,203,088個CKD新發個案，且發現居住在飲水砷濃度≥ 0.05 mg/L地區者，發生CKD的HR值為1.185 (95%信賴區間 [CI]: 1.180–1.189)。在校正年齡、性別、收入、都市化程度以及相關共病症後，經校正之HR值為1.162 (95% CI: 1.157–1.166)，仍有統計上顯著意義。此外，共病症在其中具有修飾效應作用，對於罹患三種 (含) 以上共病症之患者有更顯著的效應 (經校正之HR值[AHR]為1.178, 95% CI: 1.171–1.185)。針對台灣西南地區，也同樣發現這樣的顯著關聯性 (AHR值為1.028, 95% CI: 1.021–1.035)，該效應亦受到共病症之修飾作用影響，在罹患一到兩種共病症之患者中較明顯 (AHR值為1.079, 95% CI: 1.068–1.090)。

結論
飲水中的過量砷暴露可能會增加罹患CKD的風險，針對居住於砷暴露流行地區之居民，預防和控制高風險共病症對於降低罹患CKD的風險非常重要。

Background
In the early 1910s and late 1940s, residents of areas in southwestern and northeastern Taiwan were subject to long–term arsenic exposure through the use of high–arsenic artesian well water. Although these endemic areas currently utilize public water supply systems using surface water, many area residents may still suffer from chronic health effects caused by arsenic exposure from drinking water, such as cancers of the skin, urinary bladder, and kidney, hypertension, diabetes mellitus, and renal injury (specifically glomerular and tubular interstitial damage), which may progress to chronic kidney disease (CKD). Therefore, we conducted this nationwide population–based study in Taiwan, where the prevalence of CKD is high, to assess the potential association between arsenic exposure in drinking water and CKD, as well as the effect modifications by comorbidities.

Methods
We conducted a retrospective cohort study in Taiwan, focusing on the island as a whole, and its southwestern region specifically. Our cohorts consisted of members aged 40 years or older on January 1, 1998. Using the National Health Insurance Database, we identified patients of CKD newly diagnosed between January 1, 1998 and December 31, 2014. Arsenic levels in drinking water were assessed according to a nationwide census survey for 311 townships conducted by the government from 1974 to 1976. Hazard Ratios (HRs) contrasting CKD risk between arsenic exposure levels were estimated using Cox proportional hazard regressions and were concurrently adjusted for the effects of potential confounders. We also employed the Kaplan–Meier curve and Log–Rank test statistics to evaluate the differences in the cumulative probability of not being diagnosed with CKD between two arsenic exposure groups. Lastly, we performed stratified analyses to assess the effect modification of comorbidities.

Results
In the study cohort of 6,573,192 participants in the whole region of Taiwan, we identified 1,203,088 patients newly diagnosed with CKD during the study period and found that residents of areas with arsenic levels ≥ 0.05 mg/L in the drinking water had a HR of 1.185 (95% confidence interval [CI]: 1.180–1.189) for CKD. After adjusting for age, sex, income, urbanization level and related comorbidities, we found an adjusted HR of 1.153 (95% CI: 1.148–1.157), which was still statistically significant. Furthermore, we found the effect was modified by comorbidities, with more prominent effects on patients with more than three comorbidities (adjusted HR [AHR]=1.178; 95% CI: 1.171–1.185). In southwestern Taiwan, we also observed such a significant association between arsenic exposure and CKD (AHR=1.028, 95% CI: 1.021–1.035). The effect modified by comorbidities was more obvious on patients with one or two comorbidities (AHR=1.079; 95% CI: 1.068–1.090).

Conclusions
Excessive exposure to arsenic in drinking water may increase the risk of developing CKD. Prevention and control of the high–risk comorbidities in residents of arseniasis–endemic areas are important for decreasing the risk of developing CKD.

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