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