Biomedical Engineering Department, University of Houston, Houston, Texas, USA.
Biomedical Engineering Department, University of Houston, Houston, Texas, USA.
Kidney Int. 2024 Dec;106(6):1135-1145. doi: 10.1016/j.kint.2024.09.007. Epub 2024 Oct 5.
Most reported biomarkers for lupus nephritis (LN) have not been independently validated across cohorts. Moreover, many of the documented biomarker candidates have been reported to be elevated in LN compared to healthy controls. However, biomarkers that distinguish patients with active LN (ALN) from inactive systemic lupus erythematosus (iSLE) hold significant clinical utility. Hence, our review attempts to identify urine protein biomarkers for LN that have been independently validated across two or more cohorts and exhibit good diagnostic potential for distinguishing ALN from iSLE. PubMed and OVID were screened for studies assessing the diagnostic value of urinary biomarkers in patients with ALN compared to iSLE. Forty peer-reviewed articles were evaluated, encompassing urine biomarker data from 3,411 distinct patients. Of the 32 candidate biomarkers identified, fourteen were repeatedly reported/tested in four or more papers each, namely ALCAM, CCL2 (MCP1), CD163, HAVCR1 (KIM-1), HPGDS, ICAM-1 (CD54), ICAM-2 (CD102), IGFBP-2, LCN2, NCAM-1 (CD56), SELE (E-Selectin), SELL (L-Selectin), TNFSF12 (TWEAK), and VCAM-1, with most exhibiting C-statistics of 0.80 or more across multiple studies when discriminating patients with ALN from iSLE. The 32 reproducibly elevated biomarkers for active LN mapped to nine functional categories. The urinary proteins reported here promise to serve as a liquid biopsy for ALN. Besides representing potential candidates for diagnostic, monitoring, predictive, and prognostic biomarkers in LN, they also provide a window into potential molecular processes within the kidney that may be driving LN. Thus, ongoing advances in proteomics, which offer wider proteome coverage at increased sensitivity, are likely to further reshape our perspective of urinary biomarkers for LN.
大多数报道的狼疮肾炎 (LN) 生物标志物尚未在不同队列中进行独立验证。此外，许多已记录的生物标志物候选物与健康对照组相比，在 LN 中被报道升高。然而，能够区分活动性 LN (ALN) 和非活动性系统性红斑狼疮 (iSLE) 的生物标志物具有重要的临床应用价值。因此，我们的综述试图确定已经在两个或更多队列中进行了独立验证，并且具有良好的诊断潜力，能够区分 ALN 和 iSLE 的 LN 尿液蛋白生物标志物。在 PubMed 和 OVID 上筛选了评估 ALN 患者尿液生物标志物与 iSLE 相比的诊断价值的研究。评估了 40 篇同行评审文章，其中包含来自 3411 名不同患者的尿液生物标志物数据。在确定的 32 个候选生物标志物中，有 14 个在四个或更多论文中被重复报道/测试，即 ALCAM、CCL2（MCP1）、CD163、HAVCR1（KIM-1）、HPGDS、ICAM-1（CD54）、ICAM-2（CD102）、IGFBP-2、LCN2、NCAM-1（CD56）、SELE（E-Selectin）、SELL（L-Selectin）、TNFSF12（TWEAK）和 VCAM-1，当在区分 ALN 患者和 iSLE 时，大多数在多个研究中具有 0.80 或更高的 C 统计量。用于活动性 LN 的 32 种可重复升高的生物标志物映射到九个功能类别。报告的这些尿液蛋白有望成为 ALN 的液体活检。除了代表 LN 中诊断、监测、预测和预后生物标志物的潜在候选物外，它们还为可能驱动 LN 的肾脏内潜在分子过程提供了一个窗口。因此，蛋白质组学的不断进步，提供了更广泛的蛋白质组覆盖范围和更高的灵敏度，可能会进一步改变我们对 LN 尿液生物标志物的看法。
