男性檳榔嚼食習慣與慢性腎臟疾病的相關性研究-以人群為基礎的社區篩檢資料分析

Abstract

研究背景及目的 台灣末期腎臟疾病接受透析個案的發生率及盛行率都世界第一，關注進展到腎衰竭之前、盛行率更高的慢性腎臟疾病因此很重要，臨床指引建議應該針對高危險群篩檢出慢性腎臟疾病，提早介入以延緩進展並預防併發症。除了研究確認的高危險群，我們也需要知道台灣特殊的危險因子。台灣檳榔嚼食率高，檳榔已經被發現是糖尿病及心血管疾病危險因子，本研究目的是探討在已知危險因子外，檳榔嚼食習慣與台灣民眾慢性腎臟疾病的相關性。 材料與方法 本研究對象是1999到2005年參與基隆市社區整合式篩檢的男性民眾，共有32238人。收集的資料包括由戶籍資料庫得到的年齡及性別，問卷得到的教育水準、過去疾病史、及生活習慣包括檳榔嚼食、抽菸、喝酒、運動；篩檢進行時身體測量以得到血壓、身高、體重並計算身體質量指數，並空腹抽血檢驗生化數值，及以尿液試紙檢驗蛋白尿。綜合血壓測量、血液生化檢驗及問卷過去疾病史以定義有無各疾病；尿蛋白陽性一價以上為蛋白尿；以MDRD公式估計腎絲球濾過率(eGFR)後，將有蛋白尿或eGFR<60 mL/min/1.73m2定義為慢性腎臟疾病。本研究先以多變項logistic迴歸分析校正後檳榔嚼食習慣與慢性腎臟疾病相關性，然後分析檳榔的劑量效應。 結果 研究對象有檳榔嚼食習慣者佔16.47%，包括曾經嚼食已戒除的佔8.02%，和篩檢時仍有嚼食者佔8.45%。兩項定義指標完整18946人中慢性腎臟疾病有2769人，盛行率為14.62%(95%信賴區間14.07-15.16)，第1到第5期盛行率及95%信賴區間依序是1.60%(1.42-1.78)、5.54%(5.21-5.88)、7.06%(6.68-7.44)、0.36%(0.27-0.44)、0.05%(0.02-0.09)，第3到5期總共佔7.47%(7.08-7.86)。以台灣2006年人口年齡標準化後盛行率為10.11%(9.69-10.54)，第3至第5期總共佔4.68%(4.42-4.94)。盛行率隨著年齡上升，而且年齡愈高者嚴重度分期愈後期。本研究發現慢性腎臟疾病顯著的獨立危險因子包括年齡高、糖尿病、高血壓、高血脂、高尿酸血症、及肥胖，顯著的保護因子則有最高教育水準-學校教育超過12年。相對於不曾嚼食檳榔者，校正年齡後曾經嚼食者有慢性腎臟疾病的危險對比值為1.285 (95%信賴區間1.110-1.487)，檳榔嚼食習慣分成已戒除和仍嚼食兩類也都還顯著。多變項分析中，校正所有顯著的變項後，曾經檳榔嚼食者的慢性腎臟疾病危險對比值為1.147(95%信賴區間0.979-1.345)，嚼食習慣再分成兩類的危險對比值也都大於1但不顯著；而檳榔嚼食日劑量、期間、及累積總劑量的劑量效應分析，隨著檳榔劑量增加，慢性腎臟疾病危險對比值也增加但沒有顯著差異。以蛋白尿為依變項的分析結果與慢性腎臟疾病類似，低eGFR<60 mL/min/1.73m2為依變項的分析結果則檳榔嚼食不是危險因子。 結論 台灣的慢性腎臟疾病盛行率高，除了已知的高危險群需要篩檢，本研究發現檳榔嚼食者有慢性腎臟疾病及蛋白尿的危險對比值高但校正其他危險因子後變得不顯著，所以檳榔嚼食可能是慢性腎臟疾病或蛋白尿的危險因子或是其替代因子，在缺乏其他危險因子檢驗結果的情況，可能需要對檳榔嚼食者篩檢慢性腎臟疾病。未來應該以世代追蹤研究確認檳榔與慢性腎臟疾病的相關性及探討影響的機轉，並分析篩檢的成本效益。

Background The incidence and prevalence of end-stage-renal-disease (ESRD) on dialysis in Taiwan are highest over the world. It is crucial to emphasize on chronic kidney disease (CKD) which is the earlier disease state and is much more prevalent. Clinical guidelines recommend screening CKD in high risk groups and early intervention to delay renal function deterioration and related complication. In addition to well known risk factors, it is also important to identify special risk factors for Taiwanese. The betel-quid chewing is highly prevalent in Taiwan and is found to be the risk factor of diabetes and cardiovascular disease. The purpose of this study is to explore the association between betel quid chewing and CKD in men. Materials and methods A total of 32238 men attended the Keelung community-based integrated screening (KCIS) between 1999 and 2005. Population registration data including age and sex, questionnaire questions including educational level, past medical history, and habits of betel-quid chewing, alcohol, and smoking were collected. Anthropometric measurements included blood pressure, body height, body weight, and body mass index(BMI) calculation. Venous blood was sampled after fasting for biochemistry data. Urinary protein was also checked by urine stick. The definition of each chronic disease was based on either the measurement or laboratory abnormal result or the past medical history. Proteinuria was defined as one or more plus urine protein. Glomerular filtration rate was estimated (eGFR) by MDRD study equation. Men with either proteinuria or low eGFR less than 60 mL/min/1.73m2 were defined as CKD. Multi-variate logistic regression model was used for analysis the association between betel quid chewing and CKD in men. Dose response effect of betel-quid chewing was also evaluated by test for trend. Results The prevalence of betel-quid chewing in this study population was 16.47%, including 8.02% who quitted and 8.45% who were current chewers. Of 18946 men with complete urinary protein and eGFR data, 2769 CKD cases were noted. The prevalence was 14.62% (95% confidence interval (CI) 14.07-15.16). The prevalence and 95% CI of stage 1 to stage 5 CKD were 1.60%(1.42-1.78), 5.54%(5.21-5.88), 7.06%(6.68-7.44), 0.36%(0.27-0.44), and 0.05%(0.02-0.09) respectively. A total of 7.47%(7.08-7.86) study population were CKD stage 3 to 5. After age standardized to Taiwan population in 2006, the prevalence of CKD in Taiwanese men was 10.11%(9.69-10.54) with 4.68%(4.42-4.94) as stage 3 to 5. The prevalence and percentage of later stage both increased by age. Old age, diabetes, hypertension, hyperlipidemia, hyperuricemia, and obesity were identified as independent risk factors of CKD. The highest educational level with more than 12 school years was independent protective factor. Compared to non-chewers, the age adjusted odds ratio for CKD of betel-quid chewer was 1.285 (95%CI 1.110-1.487). It was still significant if we divided the chewers to ex-users and current users. After adjusted for all confounding factors, the adjusted odds ratio of betel-quid chewers was 1.147(95%CI 0.979-1.345). It was also more than 1 but insignificant if we divided the chewers to ex-users and current users. Regarding the dose response effect of daily dose, duration, and cumulative dose, all the adjusted odds ratios increased as the dose of betel-quid increase. But they were insignificant by test for trend . The result was similar when proteinuria was modeled as outcome variable. Betel-quid chewing was not risk factor when modeled with low eGFR<60 mL/min/1.73m2 as outcome. Conclusion The prevalence of CKD in Taiwan was high. In addition to well known high risk groups those screening were recommended, betel-quid chewing might also be a risk factor for CKD and proteinuria. But the association was insignificant after adjusting to other risk factors in our study. In the context of no other laboratory data of other risk factors available, betel-quid chewing might be a surrogate factor for CKD and might need screening. The cohort study should be considered for confirming the association between betel-quid and CKD and for exploring the mechanism. Cost-benefit analysis should also be performed if screening would be recommended.