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.

中文翻译：

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在队列独立验证中幸存下来的活动性狼疮肾炎的尿液生物标志物


大多数已报道的狼疮性肾炎 （LN） 生物标志物尚未在队列中得到独立验证。此外，据报道，与健康对照相比，许多记录在案的候选生物标志物在 LN 中升高。然而，区分活动性 LN （ALN） 和非活动性系统性红斑狼疮 （iSLE） 患者的生物标志物具有重要的临床效用。因此，我们的综述试图确定 LN 的尿蛋白生物标志物，这些标志物已在两个或多个队列中得到独立验证，并且在区分 ALN 和 iSLE 方面表现出良好的诊断潜力。筛选了 PubMed 和 OVID 用于评估尿液生物标志物对 ALN 患者与 iSLE 相比的诊断价值的研究。评估了 40 篇同行评审文章，包括来自 3,411 名不同患者的尿液生物标志物数据。在确定的 32 种候选生物标志物中，有 14 种在四篇或更多论文中重复报告/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，在区分 ALN 患者和 iSLE 时，大多数在多项研究中表现出 0.80 或更高的 C 统计量。32 个可重复升高的活性 LN 生物标志物映射到 9 个功能类别。这里报道的尿蛋白有望作为 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者外，它们还提供了一个窗口，了解肾脏内可能驱动 LN 的潜在分子过程。 因此，蛋白质组学的持续进步以更高的敏感性提供了更广泛的蛋白质组覆盖，可能会进一步重塑我们对 LN 尿液生物标志物的看法。