Betel Nut Chewing Is Associated With The Risk Of Kidney Stone Disease

Abstract:

(1) Background: Betel nut chewing injures bodily health. However, the relationship between betel nut chewing and kidney stone disease (KSD) is unknown.

(2) Methods: We analyzed 43,636 men from the Taiwan Biobank. We divided them into two groups on the status of betel nut chewing, the never-chewer and ever-chewer groups. Self-reported diagnosed KSD was defined as the subject's medical history of KSD in the questionnaire. Logistic regression was used to analyze the association of betel nut chewing and the risk of KSD.

(3) Results: The mean age of subjects in the present study was 50 years, and 16% were ever-chewers. KSD was observed in 3759 (10.3%) and 894 (12.6%) participants in the group of never-chewer and ever-chewer groups, respectively. A higher risk of KSD was found in participants with betel nut chewing compared with to without betel nut chewing (odds ratio (OR), 1.094; 95% confidence interval (95% CI), 1.001 to 1.196). Furthermore, the daily amounts of betel nut chewing >30 quids were associated with a more than 1.5-fold increase (OR,1.571; 95% CI, 1.186 to 2.079) in the odds of KSD;

(4) Conclusions: Our study suggests that betel nut chewing is associated with the risk of KSD and warrants further attention to this problem.

Keywords: epidemiologic study; kidney stone disease; nephrolithiasis; betel nut; areca nut; risk factors

HOW LONG DOES IT TAKE FOR CISTANCHE TO WORK?

1. Introduction

Kidney stone disease (KSD), also known as nephrolithiasis, is a common urological problem, resulting in a clinical burden and high cost to health care systems. Annual medical expenditures for KSD in the United States was above $2.1 billion in 2000 [1]. If the stone blocks the urinary tract, it may cause several symptoms such as severe pain in the flanks, gross hematuria, and vomiting, with the obstruction further resulting in hydronephrosis, postrenal azotemia, acute kidney injury and sepsis. Furthermore, KSD is a risk factor for chronic kidney disease, cardiovascular disease and osteoporosis [2–5]. Preventing the occurrence of KSD is an increasingly important issue and stone formation has been proven as related to genetic and environmental factors including age, gender, body mass index (BMI), diet, fluid intake, caffeine, smoking, type 2 diabetes mellitus (DM) and climate [6–11]. However, there are other risk factors that have not yet been studied, including betel nut.

Betel nut, also called areca nut, is associated with several diseases such as oral ulcers, periodontal disease and cancers of the oral cavity and esophagus [12–14]. Furthermore, it affects many systems of the human body, including the cardiovascular system, digestive system, immune system, endocrine system, nervous system and renal system [12]. Some studies have revealed that chewing betel nut could injure the kidney [15–17], but few studies have demonstrated a relationship between chewing betel nut and KSD. The aim of the present study is to explore the relationship between betel nut chewing and KSD.

2. Materials and Methods

2.1. Taiwan Biobank and Study Design

The Taiwan Biobank (TWB), a population-based biobank, consists of a cohort of more than 100,000 participants with no cancer diagnosis at baseline. The majority of participants are classed racially as Han Chinese (over 99%). TWB collects information of lifestyles, health risk factors, medical history, physical examination, blood tests and other biospecimens, with this data providing causes and mechanisms of common diseases to researchers. By combining medical information and disease-causing factors, TWB aims to facilitate better treatment and prevention and improve the health of people [18–21].

On this basis, the data from TWB (2008 to 2019) was used to examine the association between betel nut chewing and KSD in men. A total of 43,848 men were enrolled in the present study as shown in Figure 1. Participants with missing information concerning nut experience (N = 62), age (N = 1), smoking status (N = 9), alcohol status (N = 41), past history of dyslipidemia (N = 11), body mass index (N = 49), physical activity status (N = 16), status of marriage (N = 13), and status of education (N = 10) were excluded, so 43,636 men were entered into the final analysis. All participants signed the informed consent, and all investigations followed the Declaration of Helsinki. The present study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20190398).

CISTANCHE TO KIDNEY

Figure 1. Study participants were classified by status of betel nut.

2.2. Betel Nut Chewing Assessments

All participants were asked the following question: "Have you ever had experience of betel nut chewing." Participants saying "Never or only had once or twice" were assigned as the never-chewer group, and those replying "Yes" were assigned as the ever-chewer group. Among the participants with experience of betel nut chewing, the following questions were then asked: "When did you start chewing betel nuts?" "Are you a current chewer?" "How many betel nuts do you have each day?" According to the frequency of betel nut use, we divided participants into "never-chewer", " ≤10 betel nuts per day", "11–30 betel nuts per

day", and ">30 betel nuts per day."

2.3. Self-Reported Diagnosed KSD

KSD was defined by a self-reporting history of diagnosed KSD (yes/no), and the detailed questions were as below: "Have you ever had a history of diagnosed KSD?" If participants replied "yes", they were further asked, "When were you diagnosed with kidney stones?" The interviewers would repeat these questions to ensure that all participants understood and answered consistently

2.4. Statistical Methods

Volunteers in this study were divided into never-chewer and ever-chewer groups. Categorial variables are presented as percentages and continuous variables as mean ± standard deviation. Pearson χ2 test was performed to examine the differences among categorical variables, independent t-tests examined the differences among continuous variables, while logistic regression was used to analyze the association of betel nut chewing and self-reported diagnosed KSD. To examine the dosage effect between frequency of betel nut use and KSD, a subgroup of 39,113 participants with adequate information was analyzed, being

divided into 4 groups as described previously, with logistic regression being conducted to identify the association between frequency of betel nut use and KSD in this subgroup. We used R version 3.6.2 and SPSS 20.0 to perform the analyses, with a p-value < 0.05 regarded as statistically significant for all analyses.

3. Results

3.1. Clinical Characteristics of the Study Participants

Of the 43,636 men, the mean age was 50 ± 11 years, with 36,521 men (84%) in the never-chewer group and 7115 men (16%) in the ever-chewer group (Table 1). Men with betel nut chewing tended to be older, with higher blood pressure, a higher alcohol consumption rate, a higher smoking rate, a lower educational level, higher white blood cell counts, higher platelet counts, higher serum hemoglobin, total cholesterol, triglycerides, blood sugar, uric acid, creatinine, and a higher BMI than those in the never-chewer group (Table 1).

Table 1. Clinical characteristics of the study participants classified by betel nut use.

Table 1. Cont.

3.2. Betel Nut Chewing Was Associated with an Increasing Risk of KSD

A total of 7728 men had self-reported diagnosed KSD in the present study, with 6824 (6%) in the never-chewer group and 904 (12%) in the ever-chewer group. In univariable binary logistic analysis, subjects with higher BMI, smoking experience, alcohol consumption, physical activity, history of hypertension, DM, dyslipidemia, gout, and betel nut experience had higher odds of KSD. On the contrary, men with higher albumin had lower odds of KSD. Participants in the ever-chewer group were associated with a 1.25-fold increase of KSD than those in the never-chewer group (odds ratio (OR), 1.252; 95% confidence interval (95% CI), 1.159 to 1.354) (Table 2). In a subgroup analysis for subjects without a history of hypertension, DM, dyslipidemia, gout, and obesity (BMI ≥ 30 kg/m2 ), the subjects in the ever-chewer group were still associated with a higher prevalence of KSD (OR, 1.140; 95% CI, 1.014 to 1.283) (Supplementary Table S1).

Table 2. Association between parameters and KSD in univariable binary logistic analysis (N = 43,636).

After adjusting for cohort effect (using a threshold of a p-value < 0.05 from the univariate analysis (Table 2)), including age, BMI, smoking status, alcohol status, physical activity, marital status, education status, systolic blood pressure, diastolic blood pressure, past history of hypertension, past history of DM, past history of dyslipidemia, past history of gout, platelet counts, serum albumin, fasting glucose, hemoglobin A1c, total cholesterol, triglyceride, high-density lipoproteins (HDL) cholesterol, low-density lipoproteins (LDL) cholesterol, creatinine, and uric acid, subjects in the ever-chewer group were significantly associated with a higher risk of KSD than those in the never-chewer group (OR, 1.094; 95% CI, 1.001 to 1.196) (Table 3).

Table 3.Association between parameters and KSD in multivariate binary logistic analysis (N = 43,636).

Abbreviations: as Table 1 and CI: confidence interval. Adjusting for age, smoking status, alcohol status, physical activity, marital status, educational status, body mass index, SBP, DBP, history of hypertension, history of dyslipidemia, history of diabetes mellitus, history of gout, platelet count, HbA1c, serum fasting glucose, total cholesterol, TG, LDL, HDL, serum albumin, creatinine, and UA.

3.3. Dose-Response Effect between Betel Nut Chewing and the Risk of KSD

To further examine the association between the amounts of daily betel nut use and KSD, a subgroup of participants with adequate information was collected. In multivariate logistic regression analysis, subjects with ≤10 betel nuts per day, 11–30 betel nuts per day, and >30 betel nuts per day had odds ratios of 1.056 (95% CI, 0.863 to 1.291), 1.045 (95% CI, 0.870 to 1.255) and 1.571 (95% CI, 1.186 to 2.079) in the risk of KSD compared with those in the never-chewer group (Table 4). The odds increased slightly at the lower amounts of exposure (≤10 betel nuts per day and 11–30 betel nuts per day), then increased significantly at the higher amounts of exposure, which demonstrated the dose-response relationship between the amounts of daily betel nut use and the risk of KSD.

Table 4. The relative risk for KSD according to the frequency of betel nut use (N = 39,113)

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Betel Nut Chewing Is Associated With The Risk Of Kidney Stone Disease

1. Introduction