藉新型腎臟損傷生物標記探討熱壓力致腎損傷機轉

Abstract

序論 全球暖化與極端高溫氣候增加熱負荷，自1970年代，於熱帶國家中出現新興「非傳統原因之慢性腎病變」，增加健康及社會負擔。過去文獻發現高溫、脫水、高勞動力、休息不足等危險因子。目前假說提出熱暴露導致重複性脫水，並因脫水進一步引起發炎、氧化壓力增加，造成腎臟實質小管損傷。另外，許多研究也發現新型生物指標（N-乙醯-β-D-葡萄糖胺酶、腎損傷分子）可早期發現腎臟結構損傷。

目前，熱暴露導致急性腎損傷機轉仍不清楚。因此，本研究的目的為：（1）評估篩檢站護理人員在熱暴露前後，生理指標與新型腎臟損傷生物指標的變化；（2）評估早期腎臟損傷的可能危險因子；（3）藉由新型腎臟損傷生物指標，探討「早期腎臟受傷位置」，以中介效應分析，釐清熱危害致腎臟損傷的因果關係路徑。

研究方法 以事前事後比較研究設計，於2021年9–10月一處台北新冠肺炎篩檢站，18歲以上、至少工作三個月、無糖尿病、高血壓、腎結石病史、無使用非類固醇止痛藥之篩檢護理人員納入收案。分別在受試者班別的工作前後，進行核心體溫、體重的量測、全血肌酸酐即時檢驗、及後續於實驗室以酵素結合免疫吸附分析法，檢驗工作前後尿液中新型腎臟損傷（N-乙醯-β-D-葡萄糖胺酶、腎損傷分子）、發炎（白細胞介素）及氧化壓力（8-羥基去氧鳥苷）生物指標。收案人員皆經過標準化訓練，各量測儀器於收案前皆經有效校正，檢驗試劑符合品質檢驗。採用成對樣本t檢定分析熱暴露前後體溫、體重（脫水程度）、全血肌酸酐、腎臟損傷、發炎及氧化壓力生物指標變化。以廣義估計方程式（GEE）分析熱暴露影響早期腎臟損傷之相關因素。藉中介效應分析評估熱致腎損傷的因果關係路徑。

結果 共36位護理師納入結果分析，多數為20-30歲女性。在工作熱暴露後，核心體溫、脫水程度、全血肌酸酐顯著上升，且腎臟損傷（N-乙醯-β-D-葡萄糖胺酶）及氧化壓力（8-羥基去氧鳥苷）指標也顯著上升。顯著影響早期腎臟損傷之相關因素包含核心體溫上升、嚴重脫水、氧化壓力指數等變項。中介效應分析，熱壓力可藉由氧化壓力上升，導致腎臟損傷（提供48.55%解釋力），而脫水為獨立腎臟損傷影響因子。

結論： 氧化壓力作為「熱壓力致腎損傷」的中介因素，而脫水為獨立影響因子。根據結果，建議未來介入研究可採取補充水分、降溫、抗氧化等措施，評估對熱壓力造成腎損傷預防的成效。

Introduction Global warming and increasing extreme heat weather have raised heat stress, leading to the emergence of "chronic kidney disease of nontraditional cause" in tropical countries since the 1970s. Previous studies have identified risk factors such as high temperatures, dehydration, heavy loading work, and insufficient rest. Current hypotheses suggest that heat exposure causes repeated dehydration, which further leads to inflammation and increased oxidative stress, resulting in renal tubular injury. Additionally, many studies have found that novel biomarkers (N-acetyl-β-D-glucosaminidase, kidney injury molecule) can detect early renal structural damage.

The mechanisms by which heat exposure leads to acute kidney injury are still unclear. Therefore, the objectives of this study are: (1) evaluate the changes in physical parameters and novel kidney injury biomarkers in screening station nurses before and after heat exposure; (2) assess potential risk factors for early kidney injury; and (3) investigate the "location of early kidney injury" using novel kidney injury biomarkers, and clarify the causal pathways through mediation analysis.

Study methods Pre- and post-study design, this research was conducted from September to October 2021 at a COVID-19 screening station in Taipei. The study included screening nurses who were 18 years or older, had been working for at least three months, and had no medical history of diabetes, hypertension, kidney stones, or chronic use of non-steroidal anti-inflammatory drugs. Core body temperature, body weight, and whole blood creatinine were measured before and after the participants' shifts. Additionally, urine samples collected before and after work were analyzed in the laboratory using enzyme-linked immunosorbent assay (ELISA) to test for novel kidney injury biomarkers (N-acetyl-β-D-glucosaminidase, kidney injury molecule), inflammation markers (interleukins), and oxidative stress markers (8-hydroxydeoxyguanosine). All procedures were standardized, with instruments calibrated for accuracy, and test reagents met quality control standards. Paired T tests were used to analyze changes in body temperature, body weight (dehydration), whole blood creatinine, kidney injury biomarkers, inflammation, and oxidative stress biomarkers before and after heat exposure. Generalized estimating equations (GEE) were used to analyze factors related to early kidney injury due to heat exposure. Mediation analysis was conducted to clarify the causal pathways leading to heat-induced kidney injury.

Result A total of 36 nurses were included in the analysis, most of whom were women aged 20-30. After heat exposure at work, core body temperature, dehydration percentage, and whole blood creatinine significantly increased. Additionally, markers for kidney injury (N-acetyl-β-D-glucosaminidase) and oxidative stress (8-hydroxydeoxyguanosine) also showed significant increases. Factors significantly affecting early kidney injury included increased core body temperature, severe dehydration, and oxidative stress. Mediation analysis indicated that heat stress could lead to kidney injury through an increase in oxidative stress, explaining 48.55% of the effect, while dehydration was an independent factor influencing kidney injury.

Conclusion Oxidative stress acts as a mediator in "heat stress-induced kidney injury", while dehydration is an independent influencing factor. Based on the results, we suggest further intervention study using hydration, cooling, antioxidant supplementation to evaluate their effectiveness in preventing heat-stress induced kidney injury.