環境非理想溫度對於脆弱族群的腎損傷

Abstract

氣候變遷加劇環境溫度的波動，對人類的身心健康造成重大衝擊。眾多與氣候變遷相關的健康風險中，慢性腎臟病（CKD）已成為全球的重要疾病負擔；在臺灣，慢性腎臟病及末期腎病透析更長年高居健保支出首位。受到國際間對病因未明慢性腎臟病（CKDu）關注的啟發，本研究進一步探討非理想環境溫度對臺灣脆弱族群腎臟健康的影響，特別聚焦於農業工作者與居家高齡衰弱者。 針對彰化縣農民族群，回溯性研究發現非傳統病因之慢性腎臟病佔所有CKD個案的48.9%，且農民罹患CKDu的調整後盛行率勝算比比非農民高出45%至63%。高達22%的農民有脫水現象，是非農民（14%）的約兩倍，暗示熱壓力與脫水是農民CKDu的潛在危險因子。戶外熱暴露與慢性腎病存在顯著的時間滯後效應，彰化縣研究顯示腎功能受損與前1至9個月的戶外熱暴露呈正向關聯，平均氣溫每升高1°C，慢性腎病風險增加4%至22%，其中累積9個月的影響最顯著（勝算比為1.22，95%信賴區間為1.09–1.37）。此關聯在女性及農民族群中尤其顯著。然而對勞力工作者的額外分析，並未顯示CKDu風險顯著上升，這可能表示臺灣農民的腎損傷不僅由熱壓力引起，其他農業相關危害如農藥、重金屬、止痛藥等也可能是潛在病因。全國性研究同樣驗證農民有較高CKDu風險（勝算比為1.09，95%信賴區間為1.001–1.18），並且發現戶外熱暴露與整體族群慢性腎臟病風險的顯著相關。儘管許多參與者（農民24.9%，非農民7.4%）腎功能已達慢性腎臟病標準，但僅約七分之一的人接受醫師診斷，凸顯臺灣腎病診斷率普遍偏低的問題。 在前瞻型研究世代中，我們首次發現，在臺灣相對寒冷的月份（11月至4月），室內環境低溫與居家高齡衰弱者的疑似腎損傷（pKI）發生呈顯著關聯。低溫對pKI的累積滯後效應在25日以上達到顯著（勝算比為0.996，95%信賴區間為0.992–0.999），顯示溫度下降會增加pKI風險。高溫對此族群的pKI未觀察到顯著影響，這可能與高齡衰弱者主要待在室內且高溫幅度較小有關。研究進一步發現，pKI事件伴隨血清和肽素（copeptin）濃度上升、尿液嗜中性白血球明膠酶相關脂質運載蛋白（NGAL）濃度上升，以及心律變異度低頻/高頻比（LF/HF）的增加，這些生物指標變化初步顯示高齡衰弱者腎損傷的潛在病生理機轉，例如抗利尿激素路徑活化、早期腎小管間質性損傷及交感神經活性增強等。 整體而言，環境高低溫對脆弱族群腎功能有潛在負面影響，強調氣候變遷下需針對高風險群制定特殊保護策略，並提升早期診斷與監測，以強化社會韌性應對未來健康挑戰。

Climate change exacerbates environmental temperature fluctuations, significantly impacting human health. Among numerous climate-related health risks, chronic kidney disease (CKD) represents a major global burden, with CKD and end-stage renal disease dialysis consistently topping Taiwan’s healthcare expenditures. Inspired by international focus on chronic kidney disease of undetermined etiology (CKDu), this study investigates the effects of non-optimal environmental temperatures on kidney health in vulnerable Taiwanese populations, particularly agricultural workers and frail elderly receiving home care. Retrospective analyses of Changhua County farmers revealed that chronic kidney disease of nontraditional etiology accounted for 48.9% of all CKD cases, with farmers exhibiting a 45–63% higher adjusted prevalence odds ratio for CKDu compared to non-farmers. Notably, 22% of farmers showed signs of dehydration, nearly double that of non-farmers (14%), suggesting heat stress and dehydration as potential CKDu risk factors. Outdoor heat exposure was significantly associated with CKD, with a 1°C increase in average temperature linked to a 4–22% increased CKD risk over 1–9 months, with the most pronounced effect at 9 months (OR=1.22, 95% CI: 1.09–1.37). This association was particularly evident in females and farmers (females: OR=1.39, 95% CI: 1.13–1.71; farmers: OR=1.28, 95% CI: 1.11–1.49). However, analysis of manual laborers showed no significant CKDu risk elevation, indicating that farmers’ kidney injury may involve additional agricultural hazards such as pesticides, heavy metals, or analgesics. A nationwide case-control study confirmed higher CKDu risk in farmers (OR=1.09) and a significant association between outdoor heat exposure and CKD risk. Despite 24.9% of farmers and 7.4% of non-farmers meeting CKD criteria, only about one-seventh received a physician diagnosis, highlighting Taiwan’s low CKD diagnosis rate. In the prospective research cohort, for the first time, we identified a significant association between indoor low temperatures (November–April) and possible kidney injury (pKI) in frail elderly individuals (OR=0.996, 95% CI: 0.992–0.999 for cumulative lag over 25 days). High indoor temperatures showed no significant pKI effect, likely due to limited temperature fluctuations indoors. pKI events were accompanied by elevated serum copeptin, urinary NGAL, and increased heart rate variability low-to-high frequency ratio (LF/HF), suggesting pathophysiological mechanisms such as vasopressin pathway activation, early tubulointerstitial injury, and enhanced sympathetic activity. Overall, this study underscores the significant impact of extreme environmental temperatures on kidney health in vulnerable populations. It emphasizes the need for targeted protective strategies and enhanced early diagnosis and monitoring to strengthen community resilience against climate change-related health challenges.