Abstract：
BACKGROUND: Humans are exposed to uranium (U) in a variety of applications. Both animal and observational human studies support an associated U nephrotoxicity. Few statistical syntheses of the human data have been performed and these analyses are limited in the types of exposures considered.
OBJECTIVE: This study aims to evaluate the state of current evidence and to expand on existing meta-analyses by systematically evaluating kidney-associated causes of mortality in multiple U-exposed populations. This study also aims to evaluate the effect of U exposure on kidney function and biomarkers of kidney injury.
METHODS: The published and grey literature were systematically reviewed for studies that reported Standardized Mortality Ratios (SMR) for kidney cancer, chronic nephritis/nephrosis, all-cause mortality, diabetes, all circulatory/heart disease, and/or ischemic heart disease in U-exposed humans. Studies that reported kidney biomarker measures for U-exposed versus control subjects were identified separately.
RESULTS: 36 studies were included. The studies were parsed into subgroups based on setting of exposure. Analysis of kidney cancer and chronic nephritis/nephrosis mortality demonstrated an SMR of 0.93 (95CI: 0.82-1.05) and 0.82 (95CI: 0.70-0.96), respectively. The other clinical outcomes evaluated also demonstrated mortality deficits in exposed relative to unexposed individuals. Subgroup analyses demonstrated similar mortality deficits. Conversely, biomarker analyses suggested better kidney function in the controls, but none of these differences reached significance.
CONCLUSIONS: Given that most of the included mortality studies were conducted in occupational populations, the mortality deficits observed in our analyses were likely due to the healthy-worker effect. Additionally, our analyses of kidney biomarkers were severely limited by low precision due to a low number of available studies and small study-size. Future work needs to evaluate the progression of chronic and to end-stage kidney disease in community-based populations to better assess the full impact of prolonged chronic U exposure on kidney outcomes.
OBJECTIVE: This study aims to evaluate the state of current evidence and to expand on existing meta-analyses by systematically evaluating kidney-associated causes of mortality in multiple U-exposed populations. This study also aims to evaluate the effect of U exposure on kidney function and biomarkers of kidney injury.
METHODS: The published and grey literature were systematically reviewed for studies that reported Standardized Mortality Ratios (SMR) for kidney cancer, chronic nephritis/nephrosis, all-cause mortality, diabetes, all circulatory/heart disease, and/or ischemic heart disease in U-exposed humans. Studies that reported kidney biomarker measures for U-exposed versus control subjects were identified separately.
RESULTS: 36 studies were included. The studies were parsed into subgroups based on setting of exposure. Analysis of kidney cancer and chronic nephritis/nephrosis mortality demonstrated an SMR of 0.93 (95CI: 0.82-1.05) and 0.82 (95CI: 0.70-0.96), respectively. The other clinical outcomes evaluated also demonstrated mortality deficits in exposed relative to unexposed individuals. Subgroup analyses demonstrated similar mortality deficits. Conversely, biomarker analyses suggested better kidney function in the controls, but none of these differences reached significance.
CONCLUSIONS: Given that most of the included mortality studies were conducted in occupational populations, the mortality deficits observed in our analyses were likely due to the healthy-worker effect. Additionally, our analyses of kidney biomarkers were severely limited by low precision due to a low number of available studies and small study-size. Future work needs to evaluate the progression of chronic and to end-stage kidney disease in community-based populations to better assess the full impact of prolonged chronic U exposure on kidney outcomes.
摘要：
背景：人类在多种应用中暴露于铀（U）。动物和观察性人类研究都支持相关的U肾毒性。很少对人类数据进行统计合成，并且这些分析仅限于所考虑的暴露类型。
目的：本研究旨在评估当前证据的状态，并通过系统评估多个U暴露人群的肾脏相关死亡原因来扩展现有的荟萃分析。本研究还旨在评估U暴露对肾功能和肾损伤生物标志物的影响。
方法：对已发表的文献和灰色文献进行了系统综述，以研究报告肾癌的标准化死亡率（SMR），慢性肾炎/肾病,全因死亡率,糖尿病,所有的循环/心脏病,和/或暴露于U的人类的缺血性心脏病。单独鉴定报道U-暴露与对照受试者的肾生物标志物测量的研究。
结果：纳入36项研究。根据暴露的设置，将研究分为亚组。肾癌和慢性肾炎/肾病死亡率的分析显示SMR为0.93（95CI：0.82-1.05）和0.82（95CI：0.70-0.96），分别。评估的其他临床结果也表明，相对于未暴露的个体，暴露者的死亡率不足。亚组分析显示相似的死亡率缺陷。相反，生物标志物分析表明，对照组的肾功能更好，但是这些差异都没有达到显著性。
结论：鉴于大多数纳入的死亡率研究是在职业人群中进行的，我们分析中观察到的死亡率缺陷可能是由于健康工人效应.此外,我们对肾脏生物标志物的分析由于现有研究数量少和研究规模小而受到精确度低的严重限制.未来的工作需要评估社区人群中慢性和终末期肾脏疾病的进展，以更好地评估长期慢性U暴露对肾脏结局的全面影响。
目的：本研究旨在评估当前证据的状态，并通过系统评估多个U暴露人群的肾脏相关死亡原因来扩展现有的荟萃分析。本研究还旨在评估U暴露对肾功能和肾损伤生物标志物的影响。
方法：对已发表的文献和灰色文献进行了系统综述，以研究报告肾癌的标准化死亡率（SMR），慢性肾炎/肾病,全因死亡率,糖尿病,所有的循环/心脏病,和/或暴露于U的人类的缺血性心脏病。单独鉴定报道U-暴露与对照受试者的肾生物标志物测量的研究。
结果：纳入36项研究。根据暴露的设置，将研究分为亚组。肾癌和慢性肾炎/肾病死亡率的分析显示SMR为0.93（95CI：0.82-1.05）和0.82（95CI：0.70-0.96），分别。评估的其他临床结果也表明，相对于未暴露的个体，暴露者的死亡率不足。亚组分析显示相似的死亡率缺陷。相反，生物标志物分析表明，对照组的肾功能更好，但是这些差异都没有达到显著性。
结论：鉴于大多数纳入的死亡率研究是在职业人群中进行的，我们分析中观察到的死亡率缺陷可能是由于健康工人效应.此外,我们对肾脏生物标志物的分析由于现有研究数量少和研究规模小而受到精确度低的严重限制.未来的工作需要评估社区人群中慢性和终末期肾脏疾病的进展，以更好地评估长期慢性U暴露对肾脏结局的全面影响。
