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Association of betel nut chewing with chronic kidney disease: A retrospective 7-year study in Taiwan

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O r i g i n a l A r t i c l e

Association of betel nut chewing with chronic kidney disease:

A retrospective 7-year study in Taiwan

nep_1489751..757

YUEH-HAN HSU,

1,4

WEN-HSIN LIU,

2

WEI CHEN,

3,5

YI-CHUN KUO,

1

CHIH-YEN HSIAO,

1

PEIR-HAUR HUNG,

1

ING-CHING JONG,

1

PEI-CHUN CHIANG

1

and CHIH-CHENG HSU

6,7

1Division of Nephrology, Department of Internal Medicine, Chia-Yi Christian Hospital,2Division of Family Medicine, Chia-Yi Christian Hospital,3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi,4Department of Nursing, Min-Hwei College of Health Care Management, Tainan,5Department of Respiratory Therapy, China Medical University,6Department of Health Services Administration, China Medical University and Hospital, Taichung, and7Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan

KEY WORDS:

betel nut, chronic kidney disease.

Correspondence:

Dr Chih-Cheng Hsu, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan. Email: [email protected]

Accepted for publication 19 June 2011. Accepted manuscript online 7 July 2011. doi:10.1111/j.1440-1797.2011.01489.x Conflicts of Interest: None to disclose.

SUMMARY AT A GLANCE

This paper details a population-based study in Taiwan aimed at determining a possible association between Betel nut chewing and chronic kidney disease. Much larger than previous studies in the area, the authors have determined that an association exists in some subgroups of their large cohort.

ABSTRACT:

Aim:

Only few studies have reported that betel nut (BN) chewing is

inde-pendently associated with chronic kidney disease (CKD); however, the

sample size was relatively small. This study was to explore further the

association between BN chewing and CKD using a larger case series.

Methods:

We retrospectively reviewed the records of a health check-up

program from 2003 to 2009. Laboratory tests, medical history and status of

cigarette smoking, alcohol drinking and BN chewing were compared

between CKD and non-CKD groups. We checked interaction effects between

BN chewing and all other covariates, and conducted multivariate logistic

regression analysis to explore the risk of CKD with BN chewing.

Results:

A total of 27 482 participants (15 491 females and 11 991 males,

mean age 58.02

1 11.85 years) were included in the study, of whom 4519

(16.4%) had CKD and 1608 (5.9%) chewed BN. CKD prevalence in the

chewers was higher than in the non-chewers in all age groups per decade.

BN chewing was significantly associated with CKD in overall subjects (odds

ratio (OR)

= 1.23, P = 0.027) and also in the male (OR = 1.23, P = 0.035),

non-drinking (OR

= 1.62, P = 0.000), diabetic (OR = 1.27, P = 0.021), and

non-proteinuric groups (OR

= 1.30, P = 0.013). This relationship was insignificant

in female, drinking, diabetic and proteinuric groups.

Conclusion:

The association between BN chewing and CKD seemed

condi-tional on demographics, health behaviours, and underlying co-morbidities.

This association should be interpreted cautiously.

INTRODUCTION

The incidence of end-stage renal disease (ESRD) has

increased rapidly worldwide.

1

Taiwan has the highest ESRD

incidence and prevalence in the world,

2

leading to heavy

burdens on health care resources and national finance. Early

detection of potential risk factors and early treatment of

chronic kidney disease (CKD) may slow the decline of renal

function and prevent the development of severe

cardiovas-cular complications.

3

In addition to well-established CKD

risk factors, such as age, hypertension, diabetes, obesity

and metabolic syndrome, there are still other potentially

modifiable risk factors to be identified for the prevention and

management of CKD.

Betel nut (BN) is the fourth most widely used addictive

substance in the world, and BN chewers make up over 10%

of the world’s population.

4

The prevalence of BN use has

increased gradually in Taiwan, especially in rural areas.

5

In

addition to the associations with oral cancer,

6

cardiovascular

disorders,

7

hyperglycemia,

8,9

obesity,

10

metabolic syndrome,

8

type 2 diabetes mellitus,

9

liver cirrhosis

11

and increase in

urinary albumin excretion,

12

BN chewing has also been

reported to be associated with CKD.

13,14

However, the

(2)

was relatively small (n

= 677) and the adjustment factors

included were limited. In the present study, we conducted a

retrospective analysis with the currently largest available

series (27 482 participants, 4519 CKD) to explore the

in-depth relationship between BN chewing and CKD in

Taiwan.

METHODS

Participants

From 2003 to 2009, a total of 34 372 people attended a national health insurance health check-up program (NHI-CP) in Chia-Yi Christian Hospital, with 36 577 records in total; 1481 people attended the program more than once in different years with a total of 2205 extra visits. All of the participants were enrolled in this retrospective record-review study. For those receiving more than one health check-up, only the first was included. Participants with incomplete data (n= 6890) were excluded from the analysis, and a total of 27 482 participants were included. The study was approved by the Institutional Review Board of this hospital.

Methods

The NHI-CP is a formally designed physical check-up package for adults at or over the age of 40, issued by the Bureau of National Health Insurance (BNHI), Taiwan. It contains a standard lab test package, a brief questionnaire for basic demographic data (age, sex, address), health behaviours (status of cigarette smoking, alcohol drinking and BN chewing), personal medical history (including diabetes, hypertension, and hyperlipidemia), and a physical ex-amination (PE). The participants were asked to report three aforementioned health behaviours in the last 6 months as a non-user, social user or regular user. PE data include body height, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP), and body mass index (BMI) was derived from the PE data. The standard laboratory studies include serum creatinine (Scr), total cholesterol (TC), triglycerides (TG), uric acid (UA), fasting blood sugar (FBS), alanine aminotransferase (ALT), hemoglobin (Hb) and urinalysis (including bio-chemical and sediment microscopic exams), which were all measured with standard automated technol-ogy. In addition, we also calculated estimated glomerular filtration rates (eGFR) for all included participants using the Modification of Diet in Renal Disease (MDRD) formula.3Participants fasted for 12 h overnight before blood sampling in the morning.

Variable definition

Chronic kidney disease was defined as an eGFR less than 60 mL/min per 1.73 m2as calculated by the MDRD formula, and then further stratified into CKD stage 3, 4 and 5 if the eGFR was 30–59 mL/min per 1.73 m2, 15–29 mL/min per 1.73 m2 and <15 mL/min per 1.73 m2, respectively.3Hypertension (HTN) was defined as having a past personal history (regardless of whether or not they were taking medications), or a blood pressure of at least 140/90 mmHg.15 Diabe-tes mellitus (DM) was defined as a fasting plasma glucose level of 126 mg/dL or higher, or a history of DM with or without medica-tion.16Hyperlipidemia was defined as having a serum total

choles-terol level of 200 mg/dL or higher, or a triglyceride level of 200 mg/dL or higher, or a past personal history of high TC or TG with or without medication.17 Participants were defined as non-smokers if they did not smoke and as non-smokers if they smoked socially or regularly regardless of the amount they smoked. Participants were defined as non-chewers if they did not consume any BN at all; as chewers if they consumed BN socially or regularly. Likewise, partici-pants were defined as non-drinkers if they did not consume any alcohol and as drinkers if they consumed alcohol socially or regu-larly. Proteinuria was defined as having +/- or heavier protein response (including+ to 4+) in a urine dipstick test. Liver dysfunc-tion was defined as an ALT level>44 IU/L according to the upper limits of the automated technology in this hospital, and anaemia was defined as an Hb level<13 g/dL in males, and <12 g/dL in females.18 Hyperuricemia was defined as a serum UA level>7.0 mg/dL accord-ing to domestic guidelines.19

Laboratory methodology

Biochemistry tests including ALT, TC, TG, UA, and Scr were mea-sured by an automatic analyzer (Hitachi 7170, Hitachi High Tech-nologies Co, Tokyo, Japan). The test reagent for ALT was manufactured by Roche Diagnostics GmbH, Germany, and the reagents for all other biochemical tests were manufactured by Wako Pure Chemical Industries, Ltd, Japan. Hb analysis was measured by an automatic analyzer (Sysmex XE-2100/5000, Sysmex Co., Japan), and dipstick urinalysis was performed by an automated chemical analyzer (URISYS 2400, Roche Diagnostics, Germany).

Statistical analysis

Data were presented in a case-control manner, according to the status of being with and without CKD, and were reported as means and standard deviations or numbers and percentages as appropriate. Demographics, clinical characteristics and co-morbidities were ana-lyzed by the Student’s t-test or the Mann–Whitney U-test (as appro-priate) for continuous variables, and by thec2test for categorical variables.

Since age is significantly related to the decline of eGFR, we assessed the CKD prevalence of chewers versus non-chewers in different age groups (per decade until 70 years or older). The differ-ences of CKD prevalence were compared by thec2test.

To determine the association between BN chewing and CKD, we performed a multivariate logistic regression analysis (MLRA), choos-ing adjustment factors based on the followchoos-ing rationales: (i) factors that might influence CKD development, either contributing to or protecting from; (ii) potential confounding factors for CKD; and (iii) factors being both contributing factors and results of CKD. The chosen covariates included age, gender, BMI, drinking, smoking, HTN, DM, hyperlipidemia, hyperuricemia, anaemia, and proteinuria.

To test whether interaction effects (IE) existed among BN chewing and other variables, we conducted IE analyses between BN chewing and all other covariates selected for MLRA. We created a dummy variable as (BN¥ variable) and conducted separate multivariable regression analyses to test individual IE. For the covariates with significant IE, the odds ratios (OR) of CKD development related to BN chewing were estimated separately according to the statuses of these covariates.

(3)

All analyses were carried out using the SPSS for Windows statis-tical software package version 18 (SPSS Inc., Chicago, IL, USA).

P-values< 0.05 were considered to be statistically significant.

RESULTS

In total, 27 482 participants (15 491 females, 11 991 males,

mean age 58.02

1 11.85 years) were included in the analysis.

Of all participants, 4519 (16.4%) had CKD and 1608 (5.9%)

chewed BN. The prevalence of CKD in the BN chewers was

12.4%, and 16.7% in the non-chewers. The proportions of

chewers in CKD stage 3, 4, and 5 were 4.5%, 3.7% and

1.7%, respectively. Of the participants with CKD, 4.4%

chewed BN, and in the non-CKD participants, 6.1% chewed

BN (P

< 0.001).

As seen in Table 1, those who were found to have CKD

tended to be older, with a higher proportion of males, higher

BMI, higher SBP and DBP, higher Scr, TC, TG, UA, and FBS,

but lower eGFR, ALT and Hb levels. In the analysis of health

behaviours and co-morbidities, those who were found to

have CKD tended to have a higher prevalence of DM, HTN,

hyperlipidemia, proteinuria, anaemia and hyperuricemia,

but a lower proportion of BN chewing, smoking, drinking

and liver dysfunction (Table 2).

The analysis of CKD prevalence of those who chewed BN

versus non-chewers in the different age groups revealed that

in all age groups, BN chewers had a higher CKD prevalence,

although all P-values were

>0.05 in the comparisons

(Table 3).

In the MLRA models, the adjusted OR of CKD for BN

use was 1.23 (95% confidence interval (CI) 1.02–1.48,

P

= 0.027) (Table 4). IE analysis revealed that significant IE

were present among BN chewing, gender, drinking, DM and

proteinuria. For these four covariates, we conducted eight

further MLRA stratified by the level of each interacting

factor. When stratified by gender, the adjusted OR of CKD for

male BN users was 1.23 (95% CI 1.02–1.48, P

= 0.035)

(Table 5). When stratified by drinking status, the adjusted OR

of CKD for non-drinking BN users was 1.62 (95% CI 1.26–

Table 1 Characteristics of age, sex, blood pressure and laboratory profiles of the 27 482 participants stratified by chronic kidney disease (CKD) status

Overall subjects (n= 27 482) CKD(-) (n = 22 963, 83.6%) CKD(+) (n = 4519, 16.4%) Age (years) 58.021 11.85 56.001 11.80 68.321 10.19*** Male gender 11991 (43.6%) 9826 (42.8%) 2165 (47.9%)*** eGFR (mL/min/1.73 m2) 76.331 17.75 81.511 13.95 50.011 9.93*** BMI (kg/m2) 25.011 4.15 24.971 4.24 25.221 3.62*** Systolic BP (mmHg) 131.661 20.63 130.001 19.86 140.111 22.37*** Diastolic BP (mmHg) 76.951 12.23 76.691 12.03 78.271 13.16*** Creatinine (mg/dL) 0.981 0.37 0.901 0.18 1.411 0.69*** Cholesterol (mg/dL) 210.691 41.41 210.201 40.58 213.211 45.33*** Triglyceride (mg/dL) 139.431 132.25 137.001 133.48 151.781 125.10*** Uric acid (mg/dL) 6.031 1.68 5.811 1.53 7.171 1.91***

Fasting blood glucose (mg/dL) 104.671 38.10 103.721 36.57 109.461 44.77***

ALT (IU/L) 32.451 40.60 32.721 41.48 31.051 35.77*

Hemoglobin (g/dL) 14.141 1.67 14.201 1.63 13.791 1.80***

*P-value< 0.05; **P-value < 0.01; ***P-value < 0.001. Results are expressed as n (%) or means 1 standard deviation (SD). The conversion factors from Conventional Units to Standard International (S.I.) Units were: creatinine 88.4; cholesterol, 0.026; triglyceride, 0.01129; uric acid, 59.48; fasting sugar, 0.056; alanine aminotrans-ferase, 1.0; hemoglobin, 10. ALT, alanine aminotransferase; BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

Table 2 Personal behaviours and co-morbidities of the 27 482 participants

stratified by chronic kidney disease (CKD) status Overall subjects (n= 27 482) CKD(–) (n= 22 963) CKD(+) (n= 4519) Smoker 6921 (25.2%) 5850 (25.5%) 1071 (23.7%)* Drinker 4594 (16.7%) 4096 (17.8%) 498 (11.0%)*** Betel nut chewer 1608 (5.9%) 1408 (6.1%) 200 (4.4%)*** Diabetes 3640 (13.2%) 2741 (11.9%) 899 (19.9%)*** Hypertension 11727 (42.7%) 8800 (38.3%) 2927 (64.8%)*** Hyperlipidemia 989 (3.6%) 746 (3.2%) 243 (5.4%)*** Proteinuria 2808 (10.2%) 1732 (7.5%) 1076 (23.8%)*** Liver dysfunction 4391 (16.0%) 3751 (16.3%) 640 (14.2%)*** Anemia 2592 (9.47%) 1816 (7.9%) 776 (17.2%)*** Hyperuricemia 6713 (24.4%) 4519 (19.7%) 2194 (48.6%)*** *P-value< 0.05; **P-value < 0.01; ***P-value < 0.001. Results are expressed as n (%). Definitions: Chewer: participants who chewed betel nut socially or regularly in the previous 6 months by self-reporting; CKD, eGFR< 60 mL/min/ 1.73 m2calculated by the Modification of Diet in Renal Disease formula; Smoker: participants who smoked socially, occasionally or regularly regard-less of the amount in the previous 6 months by self-reporting; Drinker: partici-pant who consumed alcohol socially or regularly regardless of the amount in the previous 6 months by self-reporting; Diabetes: fasting plasma glucose level equal to or over 126 mg/dL or a known history of diabetes with or without medication; Hypertension: having known past history or blood pressure of at least 140/90 mmHg with or without medication; Hyperlipidemia: having serum cholesterol level above 200 mg/dL, or triglyceride level 200 mg/dL or above or known past history with or without medication. Proteinuria, having+/- or heavier protein response (including+ to 4+) in urine test; Liver dysfunction: ALT level>44 IU/L; Anemia, male Hb < 13 g/dL, female Hb < 12 g/dL; Hyperu-ricemia, for both genders, serum uric acid level> 7.0 mg/dL. CKD, chronic kidney disease.

(4)

2.08, P

= 0.000). When stratified by diabetes, the adjusted

OR of CKD for non-diabetic BN users was 1.27 (95% CI

1.04–1.56, P

= 0.021). When stratified by proteinuria, the

adjusted OR of CKD for non-proteinuric BN users was 1.30

(95% CI 1.06–1.60, P

= 0.013). There were no significant

ORs in the female, drinking, diabetes and proteinuric groups.

DISCUSSION

In this cross-sectional study, we found a conditional

associa-tion of BN chewing with CKD in males, non-drinkers, and

those without diabetes or proteinuria, which is unique to

previous studies. In the current study, the overall prevalence

of CKD in BN chewers seemed to be lower than in

non-chewers (12.4% vs 16.7%). However, when the data were

stratified by age per decade (Table 3), the prevalence of CKD

in BN chewers became higher than in non-chewers in all age

groups from 40 to over 70 years, although without statistical

significance. In addition, CKD prevalence increased with age

in both the BN chewers and non-chewers groups. These

results seem to support the idea that BN chewers might have

a higher CKD prevalence. The data also raised the possibility

that other factors might be involved in the pathogenesis of

CKD. BN chewing was not considered to be a main

patho-genic factor of CKD. Instead, age was an obviously important

contributor, and, as shown in Tables 1 and 2, participants

found to have CKD also had higher prevalence of some

well-established CKD pathogenic risks such as obesity,

dia-betes, hypertension, hyperlipidemia, proteinuria, anaemia

and hyperuricemia.

The proportion of BN chewing in the CKD subjects

appeared to be lower than in participants without CKD

(Table 2). This observation does not coincide with our

hypothesis that BN chewing might be associated with CKD.

However, as also shown in Table 2, the proportion of all the

modifiable variables (including smoking, drinking and BN

chewing) appeared to be lower in the participants with CKD,

and the prevalence of all non-modifiable risk factors (DM,

HTN, hyperlipidemia) in the CKD participants was

signifi-cantly higher. It seems reasonable to infer that people might

change their health behaviours as they grew older or with

poorer health. This hypothesis is supported by Tseng’s

study,

20

which reported that in older age groups, a protective

behavioural pattern was more dominant. In addition, the

Table 3 Comparison of CKD prevalence in chewers versus non-chewers stratified by age

Age range (years) CKD+ (n = 4519) P-value

Gross CKD prevalence CKD prevalence of non-chewers CKD prevalence of chewers 40~<50 299/8160 (3.7%) 265/7469 (3.5%) 34/691 (4.9%) 0.066 50~<60 454/7416 (6.1%) 415/6908 (6.0%) 39/508 (7.7%) 0.130 60~<70 1516/6385 (23.7%) 1443/6100 (23.7%) 73/285 (25.6%) 0.448 ⱖ70 2250/5521 (40.8%) 2196/5397 (40.7%) 54/124 (43.5%) 0.522

Results are expressed as n (%).

Table 4 Multivariate logistic regression analysis for post-adjustment chronic

kidney disease (CKD) odds

Odds ratio 95% confidence interval P-value

Age 1.09 1.09–1.10 0.000

Gender of male 0.82 0.76–0.89 0.000

Betel nut chewing 1.23 1.02–1.48 0.027

Smoking 1.02 0.93–1.12 0.645

Drinking 0.75 0.66–0.85 0.000

Body mass index 1.00 0.99–1.01 0.605

Hypertension 1.39 1.29–1.51 0.000 Diabetes 1.05 0.95–1.17 0.309 Hyperlipidemia 1.32 1.12–1.57 0.001 Anaemia 2.07 1.845–2.32 0.000 Proteinuria 2.43 2.19–2.69 0.000 Hyperuricemia 3.57 3.29–3.87 0.000

*P-value< 0.05; **P-value < 0.01; ***P-value < 0.001.

Table 5 Odds ratio of chronic kidney disease (CKD) with betel nut (BN)

chewing, stratified by presence and absence of variables with significant inter-action effect (gender, drinking, diabetes mellitus (DM), proteinuria)

Odds ratio 95% confidence interval P-value

Corporate a 1.23 1.02–1.48 0.027 Gender b Male 1.23 1.02–1.48 0.035 Female 0.94 0.44–2.00 0.865 Drinking b Yes 1.01 0.77–1.32 0.961 No 1.62 1.26–2.08 0.000 DM b Yes 1.11 0.73–1.69 0.621 No 1.27 1.04–1.56 0.021 Proteinuria b Yes 1.00 0.68–1.48 0.989 No 1.30 1.06–1.60 0.013

a: Multivariate logistic regression analysis conducted with all adjustment

factors, including age, gender, drinking, smoking, hypertension (HTN), DM, hyperlipidemia, hyperuricemia, body mass index, anemia and proteinuria;

b: Multivariate logistic regression analysis conducted with the rest of the

variables, in addition to specific variables under stratified conditions as presence and absence.

(5)

data in this study revealed that the proportion of BN chewing

decreased with worsening CKD severity (for CKD stage 3, 4,

and 5, the proportions of BN chewing were 4.5%, 3.7% and

1.7%, respectively). Since the questionnaire was a fixed

form authorized by the BNHI, health behaviours data were

obtained by self-reporting based on the situation in the past

6 months, so there was no access to information on a more

detailed BN chewing history (for example, the amount

con-sumed and as an ex-chewer). In addition, elderly people

might not be able to precisely remember their BN chewing

habit over the previous 5–6 months. These were potential

sources of ascertainment bias and recall bias.

As seen in Figure 1, our study results revealed a

signifi-cantly higher percentage of concurrent substance use. This is

consistent with previous research reporting that BN chewers

are more likely to use alcohol and cigarettes as well.

21

Such

concurrent substance use represents certain lifestyle patterns

that might exert clusters of health effects simultaneously and

confer a higher health risk. Current relevant evidence has

reported additive effects on chronic hepatitis B, chronic

hepatitis C and hepatoma,

22

oral cavity cancer,

23

and calcium

urolithiasis.

24

This should be dealt with seriously by the

rel-evant health authorities, for example, by sponsoring more

health education activities targeting all three risky

behav-iours at the same time.

As shown in Table 4, our study results revealed a reduced

CKD risk with alcohol drinking (OR, 0.75, 95% CI 0.66–0.85,

P

= 0.000). This is consistent with previous research

report-ing an inverse association between alcohol consumption

and renal dysfunction.

25

Alcohol consumption in moderate

amounts has been acknowledged to be a protective factor for

cardiovascular health. For the kidneys, oxidative stress and

endothelial dysfunction, which are inter-related, are

consid-ered to play a role in the pathophysiology of many renal

diseases. Ethanol and non-alcoholic wine components,

espe-cially polyphenols, have been shown to influence oxidative

balance and endothelial function, and exert favourable

effects on kidneys in both animal and human studies.

26

Our study found four significant interaction factors with

BN chewing: gender, drinking, DM, and proteinuria. Table 5

presents the ORs of CKD with BN chewing in the different

stratification groups. A thorough analysis of the intertwining

interactions among these factors was beyond the scope of

this article. However, as male gender constituted the

major-ity of the BN chewers, it seems reasonable that the ORs and

confidence intervals were almost identical with the overall

values. For the drinking, diabetic and

non-proteinuric groups, the ORs and confidence intervals were

similar, implying that they might be regarded as background

situations on which BN chewing exerted a similar influence.

However, when different situations (drinking, diabetes,

pro-teinuria) were involved, such significant associations

disap-peared. To our best knowledge, there is no available research

discussing the interaction effects of BN chewing and diabetes

or other health behaviours. For the diabetic patients, the

disease itself is a well-known CKD risk so that the relative

impacts of BN chewing on CKD seemed ‘buffered’ and

became non-significant. For drinkers, a lower OR of CKD

was associated with BN chewing, implying that drinking

seemed to exert a protective effect as discussed in the

previ-ous paragraph. As such, we should be cautiprevi-ous about the

interpretation of the results; the interacting effects of these

covariates on the risk of CKD with BN chewing should be

researched further.

In addition to the biases discussed earlier, there are several

other limitations to this study. This was a retrospective

cross-sectional study based on the results of a health check-up

program in a single hospital setting. Sampling and

ascertain-ment bias might arise from several aspects. First, lab

diag-noses were made with only one urine sample and blood

tests, which might not be able to validate the true renal

function. Second, the participants took the initiative to

undergo the health check-up program in this hospital, and

they might have had a higher socio-economic position or

education level, been more alert to their own health

situa-tion, or already had certain ailments, and so not be

repre-sentative of the general population. These factors were

sources of selection bias. Another limitation is that the

ques-tionnaire on health behaviours did not include detailed

quantitative assessment (duration and amount) of BN

con-sumption, nor did it include previous abstinence history.

Under such circumstances, a substantial temporal

relation-ship and dose-effect relationrelation-ship between BN chewing and

CKD cannot be concluded.

However, due to the following reasons, this study still can

provide valuable information. First, this is currently the

largest series studying the association of BN chewing and

CKD. Second, the Chia-Yi region is an area with lower

average income and a large elderly population. According to

a national statistics report, the national average proportion of

elderly people in Taiwan in 2009 was 10.6%, and the

com-peting figure in the Chia-Yi region (Chia-Yi City and Chia-Yi

County combined) was 14.0%.

27

The average family income

in this area is approximately 20% lower than the national

average.

28

The population in this study was therefore very

different from the populations in previous Taiwanese

Fig. 1 Comparison of the proportion of smokers and drinkers in chewing

(6)

research.

29

Third, our study not only agreed with previous

research in this field,

13,14

but also added more adjustment

factors (hyperuricemia and proteinuria) for MLRA, opening

a new field of IE due to life patterns, especially the effect of

alcohol drinking on kidney disease. We also found a

‘condi-tional’ association of BN chewing and CKD, which is unique

to previous studies and contributes to existing knowledge.

Further investigations are needed for prospective

longitudi-nal cohort studies, including a detailed history of BN

chewing amount, duration, and previous abstinence history.

Also, further analysis of life patterns and the complex

inter-actions of the items therein, and especially the effect of

alcohol drinking on renal health are needed.

In conclusion, BN chewing, as a personal life pattern, had

intricate interactions with gender, drinking, DM and

pro-teinuria. We found a significant association between BN

chewing and CKD in male, non-drinking, non-diabetes and

non-proteinuria; however, such results should be interpreted

cautiously. Further studies should be conducted to delineate

the relationship between BN chewing and those who drink

alcohol, and those with diabetes or proteinuria.

ACKNOWLEDGEMENTS

The authors would like to express sincere gratitude to Ms

Fang-Yun Hu and Mr Jia-En Lai for assisting with data

man-agement.

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數據

Table 1 Characteristics of age, sex, blood pressure and laboratory profiles of the 27 482 participants stratified by chronic kidney disease (CKD) status
Table 4 Multivariate logistic regression analysis for post-adjustment chronic kidney disease (CKD) odds

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