Division of Rheumatology, Schroeder Arthritis Institute, University Health Network, Toronto, Canada.
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Appl Lab Med. 2022 Oct 29;7(6):1450-1467. doi: 10.1093/jalm/jfac036.
Lupus nephritis (LN) is one of the most common severe organ manifestations of systemic lupus erythematosus (SLE). LN is associated with significant morbidity and mortality in SLE patients, as up to 20% of patients progress to end-stage renal disease (ESRD). The clinical manifestations of LN are variable, ranging from asymptomatic proteinuria to a myriad of manifestations associated with nephritic and nephrotic syndromes and ESRD. It is therefore important to screen all SLE patients for LN.
Urinalysis is a useful screening test in LN. Quantification of proteinuria can be performed with either a urine protein-to-creatinine ratio or 24-h urine sample collection for protein. Renal biopsy remains the gold standard for diagnosis of LN. Traditional serum biomarkers used to monitor SLE and LN disease activity and flares include anti-double-stranded DNA antibodies and complement components 3 and 4. Other nonconventional biomarkers found to correlate with LN include anti-C1q and surrogate markers of type 1 interferon regulatory genes (INF gene signature). Potential urinary biomarkers for LN include monocyte chemoattractant protein 1, neutrophil gelatinase-associated lipocalin, tumor necrosis factor-like inducer of apoptosis, and vascular cell adhesion molecule 1.
Although studies have shown promising results for the use of alternative biomarkers, these require validation in prospective studies to support their use. Renal remission rates in patients receiving standard of care therapy for induction and maintenance treatment of LN remain low. This has prompted further research in newer therapeutic targets in LN ,which have shown promising results.
狼疮肾炎(LN)是系统性红斑狼疮(SLE)最常见的严重器官表现之一。LN 与 SLE 患者的高发病率和死亡率相关,高达 20%的患者进展为终末期肾病(ESRD)。LN 的临床表现多种多样,从无症状蛋白尿到与肾炎和肾病综合征及 ESRD 相关的多种表现。因此,对所有 SLE 患者进行 LN 筛查非常重要。
尿液分析是 LN 的一种有用的筛查试验。蛋白尿的定量可以通过尿蛋白与肌酐比值或 24 小时尿液样本收集进行。肾活检仍然是 LN 诊断的金标准。用于监测 SLE 和 LN 疾病活动和发作的传统血清生物标志物包括抗双链 DNA 抗体和补体成分 3 和 4。其他与 LN 相关的非传统生物标志物包括抗 C1q 和 1 型干扰素调节基因(INF 基因特征)的替代标志物。潜在的 LN 尿液生物标志物包括单核细胞趋化蛋白 1、中性粒细胞明胶酶相关脂质运载蛋白、肿瘤坏死因子样凋亡诱导因子和血管细胞黏附分子 1。
尽管研究表明替代生物标志物的使用有前景,但这些标志物需要在前瞻性研究中进行验证,以支持其使用。接受 LN 诱导和维持治疗标准治疗的患者的肾脏缓解率仍然较低。这促使人们对 LN 中的新治疗靶点进行了进一步研究,这些研究取得了有前景的结果。