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新型生物标志物对职业性接触二氧化硅工人慢性肾脏病的预测价值。

Predictive value of novel biomarkers for chronic kidney disease among workers occupationally exposed to silica.

机构信息

Department of Occupational and Environmental Medicine, Faculty of Medicine, 63527Cairo University, Cairo, Egypt.

Medical Biochemistry and Molecular Biology, Faculty of Medicine, 63527Cairo University, Cairo, Egypt.

出版信息

Toxicol Ind Health. 2021 Apr;37(4):173-181. doi: 10.1177/0748233721990304. Epub 2021 Feb 16.

Abstract

There is a pressing need to find reliable biomarkers for the early diagnosis of silica-induced nephropathy. Abundant genes are upregulated in damaged kidneys with subsequent protein products appearing in the urine. Liver-type fatty acid-binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) are among the most promising. Our objective was to study the importance of L-FABP and KIM-1 genes and their urinary proteins in the early detection of silica-induced renal injury, as compared with other conventional biomarkers. A cross-sectional study was conducted among 90 pottery workers occupationally exposed to silica, as compared to 90 controls. A full history taking and complete clinical examination were performed. Levels of serum creatinine, liver enzymes, urinary silicon, KIM-1, and L-FABP gene expression and protein products were measured. Estimated glomerular filtration rate (eGFR) was calculated, and abdominal ultrasound was performed. The results showed that the silica-exposed group had a statistically significant increase in serum creatinine and urinary silica, as well as a significant decrease in eGFR. Additionally, a significant increase in KIM-1 and L-FABP gene expression, associated with a significant increase in their urinary protein, was found among the exposed group. A positive correlation between urinary silica level and L-FABP gene expression was also found. A receiver operating characteristic curve analysis for L-FABP and KIM-1 gene as predictors for silica-induced nephropathy showed that L-FABP gene and protein specificity were greater than the KIM-1 gene and protein. Taken together, these findings suggest that the L-FABP gene and its protein product may be used as early indicators for renal injury among silica exposed workers.

摘要

迫切需要找到可靠的生物标志物来早期诊断二氧化硅诱导的肾病。大量基因在受损肾脏中上调,随后其蛋白质产物出现在尿液中。肝型脂肪酸结合蛋白(L-FABP)和肾损伤分子 1(KIM-1)是最有前途的标志物之一。我们的目的是研究 L-FABP 和 KIM-1 基因及其尿蛋白在早期检测二氧化硅诱导的肾损伤中的重要性,并与其他常规生物标志物进行比较。我们进行了一项横断面研究,比较了 90 名职业性暴露于二氧化硅的陶瓷工人和 90 名对照者。进行了全面的病史采集和全面的临床检查。测量了血清肌酐、肝酶、尿硅、KIM-1 和 L-FABP 基因表达和蛋白产物的水平。计算了估算的肾小球滤过率(eGFR),并进行了腹部超声检查。结果表明,暴露组的血清肌酐和尿硅水平显著升高,eGFR 显著降低。此外,暴露组还发现 KIM-1 和 L-FABP 基因表达显著增加,与其尿蛋白显著增加相关。尿硅水平与 L-FABP 基因表达之间也存在正相关。L-FABP 和 KIM-1 基因作为预测二氧化硅肾病的指标的受试者工作特征曲线分析表明,L-FABP 基因和蛋白的特异性大于 KIM-1 基因和蛋白。综上所述,这些发现表明,L-FABP 基因及其蛋白产物可作为暴露于二氧化硅的工人肾损伤的早期指标。

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