尿液外泌体来源hsa_circ_0008925与IgA肾病肾脏纤维化 的相关性研究

Urinary exosomal-derived hsa_circ_0008925 as a biomarker for estimation of renal fibrosis in patients with IgA nephropathy

目的:评估尿液外泌体中hsa_circ_0008925表达量作为IgA肾病(IgAN)肾脏纤维化潜在生物标志物的价值。方法:收集30例经肾穿刺活检病理诊断为IgAN患者和34例健康对照者的晨尿,超速离心后收集尿液外泌体。RT-qPCR检测尿液外泌体hsa_circ_0008925表达水平,并分析其与临床资料和病理参数的相关性。ROC曲线评价尿液外泌体hsa_circ_0008925表达量对IgAN肾脏纤维化的诊断价值。结果:IgAN组尿液外泌体hsa_circ_0008925表达量较健康对照组升高(P<0.001),且肾脏中-重度纤维化患者尿液外泌体hsa_circ_0008925表达水平较无-轻度纤维化患者升高(P<0.05)。尿液外泌体hsa_circ_0008925表达量与血肌酐、胱抑素C呈正相关,与肾小球滤过率(eGFR)呈负相关。ROC曲线分析提示尿液外泌体hsa_circ_0008925表达量可作为诊断IgAN肾脏纤维化的生物标记物,诊断阈值为0.089,灵敏度为72.7%,特异度为87.5%。结论:尿液外泌体中hsa_circ_0008925表达量与肾功能参数和肾间质纤维化程度密切相关,可作为诊断IgAN患者肾脏纤维化的新型、无创性生物标志物。

Objective:To assess the value of exosomal hsa_circ_0008925 expression in urine as a potential biomarker for estimation of renal fibrosis in patients with IgA nephropathy.Methods:Morning urine was collected from 30 patients with IgA nephropathy pathologically confirmed by renal puncture biopsy and another 34 healthy control subjects.Urine exosomes were obtained via ultracentrifugation.Quantitative reverse transcription PCR(RT-qPCR)was used to detect the expression level of exosomal hsa_circ_0008925 in the urinary specimens,and the correlation of exosomal hsa_circ_0008925 expression with the clinical information and pathological parameters.Receiver operating characteristic(ROC)curve was used to evaluate the value of urinary exosomal hsa_circ_0008925 expression level for diagnosis of renal fibrosis in patients of IgA nephropathy.Results:The expression of hsa_circ_0008925 in urinary exosomes in IgAN group was higher than that in healthy control group(P<0.001),and higher in patients with moderate to severe renal fibrosis than those without or mild renal fibrosis(P<0.05).The level of hsa_circ_0008925 expressed in urinary exosomes was positively correlated with serum creatinine and cystatin C,yet negatively with glomerular filtration rate(eGFR).ROC curve analysis indicated that urinary exosome-derived hsa_circ_0008925 could be used as a biomarker for estimation of renal fibrosis from IgA nephropathy.The diagnostic threshold,sensitivity and specificity were 0.089,72.7%and 87.5%,respectively.Conclusion:The expression of hsa_circ_0008925 in urinary exosomes is closely related to renal function and the degree of renal fibrosis,suggesting that this circular RNA can be used as a novel and non-invasive biomarker for the diagnosis of renal fibrosis in patients with IgA nephropathy.