Associations between Arsenic in Drinking Water and the Occurrence of Chronic Kidney Disease: A Nationwide Population-Based Study in Taiwan

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The Associations between Arsenic in

Drinking Water and the Occurrence of

Chronic Kidney Disease: A Nationwide

Population-Based Study in Taiwan

Ya-Yun Cheng

Department of Environmental and Occupational Health College of Medicine, National Cheng Kung University

Tainan, Taiwan

01 Sep. 2016

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Conflict of Interest (COI)

I have no financial interests to disclose

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Arsenic

Important

Nevertheless, epidemiology studies on the

association between arsenic exposure and the

occurrence of CKD / ESRD are still limited.

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Objective

1.

To evaluate the associations between arsenic

exposure and the occurrence of CKD / ESRD

in Taiwan.



We conducted a nationwide population-based

study including both the BFD endemic area

and other areas in Taiwan.

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Materials and methods

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Arsenic exposure index



Data on well water arsenic were obtained from a

nationwide survey conducted by the Taiwan

Provincial Institute of Environmental Sanitation

using the standard mercuric bromide stain method.

(Lo et al.,1977; APHA, 1985)

 There were more than 80,000 wells, mostly

between 1974 and 1976, and were available for 311 townships (85%).

 According to the cut-offs adopted by the survey reports, which was the regulatory standard at the time of the survey, we defined a high arsenic level as ≥ 50 µg/L

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Jan 1, 1996

Jan 1, 1998

Dec 31, 2010

New ESRD cases once diagnosis with Catastrophic illness code 001 Prevalent

CKD / ESRD

Follow up 13 years

Allowing at least 24 months wash-out period

New CKD cases 3 times OPD diagnosis by a psychiatrist

LHID2000 Population-based ecological cohort study:

1,000,000 random sampling enrollees during 1996-2010 Adjust comorbidity

SL Wang, 2003 National Health Insurance (NHI)

Longitudinal Health Insurance Database (LHID)

Evaluate the associations between arsenic exposure and the occurrence of CKD / ESRD.

Drinking history Address at 1998 Age ≥40 at 1998

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Risk factors of CKD

 Epidemiological and clinical evidence have shown a link between hypertension, diabetes, obesity, and

metabolic syndrome (Comorbidity) and the onset and progression of CKD.

 SEX, Age, Edu, SES (Yang WC, 2008; Wen CP, 2008)

 Western medicines

 NSAID (non-steroidal anti-inflammatory drugs)

 Acetaminophen (Chiu et al. 2008; Wen et al. 2008; Lai et al. 2009; Lai et al. 2010)

 Chinese herbal medicine (Aristolochic acid)

(Vanherweghem JL, 1993; Yang CS, 2000; Chang CH, 2001; Yang HY, 2006)

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Disease ICD-9-CM / A-CODE Criteria CKD 016.0, 095.4, 189.0, 189.9, 223.0, 236.91, 250.4,

271.4, 274.1, 283.11, 403.01, 404.02, 404.03, 440.1, 442.1, 447.3, 572.4, 580–589, 590-591, 593, 642.1, 646.2, 753.12–753.17, 753.19, 753.2, 794.4.

≧3 OPD visits

ESRD Dialysis 585-586 combined with copayment code ‘‘001’’

(indicated the presence of a Catastrophic illness)

1 OPD visits

Hypertension 401- 405, A260 ≧3 OPD visits

Diabetes 250, A181 ≧3 OPD visits

Hyperlipidemia 272.0-272.4, A182 ≧3 OPD visits

CAD 410-414 ≧3 OPD visits

Stroke 430-438 ≧3 OPD visits

Malignancy 140–208 ≧3 OPD visits

Assessment of kidney disease and comorbidity

International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM)

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Statistic

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Chi-square test, T-test, ANOVA

• Cox PH regression (Survival analysis): CKD ESRD

 Kaplan–Meier, Log-rank

 Cox regression: Hazard Ratio, 95% C.I.

 Single, multiple, backward stepwise (include p<0.05;

exclude p>0.15)

•

SAS 9.3 + SPSS1 17.0

•

Two-side p<0.05

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123 Townships with high

arsenic levels (≥ 50 µg/L)

were clustered in the

southwestern and

northeastern coast regions.

Fig. 1 Map of maximum

arsenic concentration

in each township.

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Fig. 2 Flow chart of the

nationwide cohort study

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1-1

TABLE-1 Cox regression models for occurrence of chronic kidney disease (N=362,505).

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1-2

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1-3

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Fig. 3 Kaplan–Meier survival analysis of CKD

Log-Rank test: p < 0.05

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2-1

TABLE-2 Cox regression models for occurrence of end-stage kidney disease (N=362,505).

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2-2

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2-3

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Fig. 4 Kaplan–Meier survival analysis of ESRD

Log-Rank test: p < 0.05

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Strengths and limitations

 A large sample size and a long duration: therefore, the results should be more reliable than those from smaller case-control or cross-sectional studies.

 Ecological fallacy.

 Ours study using resident area measurements

instead of personal exposure data: series of studies have been conducted using similar approaches and identified increased risk of cerebrovascular

disease, pterygium, and liver cancer.

(Lin et al., 2008; Cheng et al., 2010; Chung et al., 2013; Lin et al., 2013)

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Conclusion

 Using 50 µg/L as the cut-off, we found that a

higher level of arsenic in the drinking water was positive associated with AHR of 1.10 (95% CI:

1.08-1.12, p < 0.001) for the occurrence of CKD / AHR of 1.07 (95% CI: 1.01-1.14, p < 0.05) for the occurrence of ESRD in Taiwan, independent of

most documented risk factors including age, sex, SES, Hypertension, Hyperlipidemia, Stroke, CAD, diabetes mellitus (DM), and Malignancy.

 Intervention programs should be implemented in endemic areas of exposure to slow the occurrence of kidney disease.

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Acknowledgements

 This work was supported by Grants NSC102-

2314-B-006 -026-MY2 and MOST-104-2314-B- 006 -021 -MY2 from the Ministry of Science and Technology of Taiwan, R.O.C.

 The database in our study was established by the National Health Insurance Research Database (NHIRD).

 Co-author:

 How-Ran Guo (M.D., Sc.D.), Junne-Ming Sung (M.D.), Yu-Tzu Chang (M.D.)

 Travel Awards from ISEE 2016

 Taiwan Epidemiology Association (TEA) Award

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