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尿 miR-106a 诊断 IgA 肾病:肾脏疾病的液体活检。

Urinary mi-106a for the diagnosis of IgA nephropathy: Liquid biopsy for kidney disease.

机构信息

Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

出版信息

Clin Chim Acta. 2022 May 1;530:81-86. doi: 10.1016/j.cca.2022.03.006. Epub 2022 Mar 9.

Abstract

Urinary micro-RNA (miRNA) level may serve as non-invasive disease markers for immunoglobulin A nephropathy (IgAN), but urinary miRNA targets identified in previous studies may represent kidney scarring rather than being specific for IgAN. We aim to identify urinary miRNA targets for the diagnosis of IgAN by including hypertensive nephrosclerosis (HTN) as a control group. Methods In the development cohort, we performed complete miRNA profiling of urinary sediment in 33 patients with IgAN, 9 with HTN, and 9 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 72 IgAN, 34 HTN, and 20 healthy controls. Results In the development cohort, we identified 6 miRNA targets with urinary levels significantly increased in IgAN as compared to both HTN and CTL. In the validation study, all 6 miRNA targets remained increased than the other groups, although the result of miR-345 did not reach statistical significance. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-106a level for the diagnosis of IgAN was 0.742 (p < 0.0001), and the diagnostic performance was not further improved by having additional miRNA targets. At the cut-off ≥ 800 copy per 1000 copies of housekeeping gene, urinary miR-106a has 100% sensitivity and 14.8% specificity in detecting IgA nephropathy. Conclusions We identified 6 miRNA targets whose urinary levels are significantly elevated in IgAN, and urinary miR-106a level has an excellent sensitivity for the identification of IgAN. Further validation studies are needed to confirm its role in disease screening.

摘要

尿 microRNA(miRNA)水平可作为免疫球蛋白 A 肾病(IgAN)的非侵入性疾病标志物,但以前研究中鉴定的尿 miRNA 靶标可能代表肾脏瘢痕形成,而不是特异性针对 IgAN。我们旨在通过将高血压性肾硬化症(HTN)作为对照组来鉴定用于 IgAN 诊断的尿 miRNA 靶标。

方法 在开发队列中,我们对 33 例 IgAN 患者、9 例 HTN 患者和 9 例健康对照者(CTL)的尿沉渣进行了完整的 miRNA 谱分析。通过 72 例 IgAN、34 例 HTN 和 20 例健康对照者的独立验证队列来定量潜在的 miRNA 靶标。

结果 在开发队列中,与 HTN 和 CTL 相比,我们发现 IgAN 患者尿液中 6 个 miRNA 靶标的水平显著升高。在验证研究中,所有 6 个 miRNA 靶标仍高于其他组,尽管 miR-345 的结果未达到统计学意义。尿 miR-106a 水平诊断 IgAN 的受试者工作特征(ROC)曲线下面积(AUC)为 0.742(p<0.0001),并且通过增加额外的 miRNA 靶标,诊断性能没有进一步提高。在截断值≥800 拷贝/1000 个管家基因拷贝时,尿 miR-106a 对 IgA 肾病的检测具有 100%的敏感性和 14.8%的特异性。

结论 我们鉴定了 6 个 miRNA 靶标,其尿水平在 IgAN 中显著升高,尿 miR-106a 水平对 IgAN 的识别具有极好的敏感性。需要进一步的验证研究来确认其在疾病筛查中的作用。

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