探討尿液中黴菌毒素與腎臟功能與早期損傷指標之 關聯性:以台灣農業社區為例

Abstract

慢性腎臟病在臺灣具有高盛行率，除傳統風險因子外，環境暴露也扮演重要角色。氣候變遷加劇了農作物遭受真菌污染的風險，使具有腎毒性之黴菌毒素暴露成為重要的公共衛生議題。然而，國內目前缺乏多重黴菌毒素的生物偵測數據，國際上亦缺乏其與人類早期腎臟損傷指標連結的流行病學證據。本研究以臺灣農業社區居民為研究對象，於2022至2025年間招募195位農業社區居民，利用極致液相層析串聯質譜儀 (UPLC-MS/MS) 分析尿液中9種目標黴菌毒素濃度 (AFB1, CIT, DON, FB1, OTA, ZEN, AOH, NIV, STER)，並以肌酸酐進行稀釋校正，探討單一及多重黴菌毒素暴露與早期腎損傷指標微量白蛋白與尿液肌酸酐比值 (Albumin to creatinine ratio, ACR) 與N-乙醯-β-D-氨基葡萄糖苷酶與尿液肌酸酐比值 (N-acetyl-β-D-glucosaminidase to creatinine ratio, NAGCr) 以及基於肌酸酐估算之腎絲球過濾率 (Estimated glomerular filtration rate based on creatinine, eGFRCr) 與基於血清胱蛋白估算之腎絲球過濾率 (Estimated glomerular filtration rate based on cystatin C, eGFRCys) 之統計關聯與潛在生物學機制。研究結果顯示，受試族群之黴菌毒素總檢出率高達82%，以脫氧雪腐鐮刀菌烯醇 (DON) 與橘黴素 (CIT) 為主要黴菌毒素，檢出率分別為56%與44%，且有58.7%的檢出者呈現多種毒素共同檢出的現象。多元線性迴歸模型分析發現，在校正年齡、性別、糖尿病、高血壓病史、中藥及非類固醇消炎止痛藥服用習慣後，尿液CIT濃度與反應腎絲球屏障受損之ACR (β = 0.154, p = 0.038) 及反應近曲小管早期損傷之NAGCr (β = 0.170, p = 0.002) 皆呈顯著正相關。貝葉斯核機器迴歸 (Bayesian kernel machine regression, BKMR) 模型進一步發現當混合暴露於多重黴菌毒素時，受試者體內預測之NAGCr變化量隨毒素濃度增加而顯著上升，且後驗納入機率排序證實CIT在混合暴露所致之早期腎損傷中扮演最關鍵的主導角色。本橫斷性研究證實尿液中黴菌毒素與早期腎臟損傷具有潛在關聯性，在氣候變遷加劇真菌污染風險的趨勢下，本研究所建立之尿液中黴菌毒素濃度數據與初步關聯性分析結果，可作為未來評估農業社區腎臟健康與環境毒素暴露風險之流行病學基礎。

Chronic kidney disease (CKD) has a high prevalence in Taiwan, and in addition to traditional risk factors, environmental exposures also play an important role. Climate change has increased the risk of fungal contamination in agricultural crops, making exposure to nephrotoxic mycotoxins an important public health issue. However, there is currently a lack of biomonitoring data on multiple mycotoxins in Taiwan, and epidemiological evidence linking these exposures to early markers of kidney injury in humans is also limited internationally. This cross-sectional study recruited 195 residents from agricultural communities in Taiwan between 2022 and 2025. Urinary concentrations of nine mycotoxins (AFB1, CIT, DON, FB1, OTA, ZEN, AOH, NIV, and STER) were quantified using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS), with creatinine adjustment applied to account for urine dilution. The study investigated the statistical associations and potential biological mechanisms between single and multiple mycotoxin exposures and early kidney injury markers, including albumin to creatinine ratio (ACR), N-acetyl-β-D-glucosaminidase to creatinine ratio (NAGCr), as well as markers of kidney function, including estimated glomerular filtration rate based on creatinine (eGFRCr) and estimated glomerular filtration rate based on cystatin C (eGFRCys). The results showed that the overall detection rate of mycotoxins in the study population reached 82%. Deoxynivalenol (DON) and citrinin (CIT) were the predominant mycotoxins, with detection rates of 56% and 44%, respectively. Co-occurrence of multiple mycotoxins was observed in 58.7% of participants. Multiple linear regression analysis revealed that, after adjusting for age, sex, diabetes, hypertension, use of traditional Chinese medicine, and nonsteroidal anti-inflammatory drugs (NSAID), urinary CIT concentration was significantly positively associated with ACR (β = 0.154, p = 0.038) and with NAGCr (β = 0.170, p = 0.002). Bayesian kernel machine regression (BKMR) further indicated a positive overall mixture effect on NAGCr, with CIT contributing the highest posterior inclusion probability, suggesting a dominant role in early kidney injury under mixture exposure. In conclusion, urinary mycotoxin exposure was prevalent in this agricultural population and was associated with early kidney injury markers. These findings provide biomonitoring evidence and support the need for further investigation into environmental mycotoxin exposure and kidney health, particularly under the increasing risk of fungal contamination associated with climate change.