Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, 27106Karolinska Institute, Stockholm, Sweden.
Division of Rheumatology, Department of Medicine DIMED, Padua University Hospital, Padua, Italy.
Lupus. 2023 Feb;32(2):252-262. doi: 10.1177/09612033221145534. Epub 2022 Dec 12.
BACKGROUND: Lupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management. OBJECTIVE: To investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN. PATIENTS AND METHODS: Levels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured. RESULTS: Normalized u-Gal-3BP levels were higher in LN patients compared to the other groups (). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, ). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed () Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort. CONCLUSION: Given its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.
背景：狼疮肾炎 (LN) 是系统性红斑狼疮 (SLE) 的一种主要且严重的器官受累，其诊断和治疗需要进行肾活检，这是一种有创的操作。非侵入性尿液生物标志物是支持 LN 诊断和管理的一个活跃研究领域。 目的：探讨尿半乳糖凝集素-3 结合蛋白 (u-Gal-3BP) 作为活检证实的 LN 肾脏疾病候选生物标志物的作用。 患者和方法：通过 ELISA 以横断面方式研究了 270 名受试者的 u-Gal-3BP 水平：86 名 LN 患者、63 名无肾脏受累的活动期 SLE 患者、73 名无活动期疾病的 SLE 患者和 48 名年龄和性别匹配的人群对照（PBC）。此外，通过 ELISA 分别分析尿液样本以用于其他肾脏病理标志物：中性粒细胞明胶酶相关脂质运载蛋白 (NGAL)、骨桥蛋白 (OPN)、肾损伤分子-1 (KIM-1) 和半乳糖凝集素-3 (Gal-3)。所有研究分子的浓度均按尿肌酐水平进行标准化。在 10 名患者中，测量了治疗后的生物标志物水平。 结果：与其他组相比，LN 患者的标准化 u-Gal-3BP 水平更高（）。比较不同的 LN 类型，增殖性（III/IV 级）和膜性（V 级）形式的患者 u-Gal-3BP 水平高于系膜性（II 级）形式（）。在增殖性形式中，u-Gal-3BP 水平与肾活检中的活动指数相关（r = 0.42，）。此外，在接受重复肾活检和治疗前后尿液取样的 10 名患者亚组中，观察到 u-Gal-3BP 显著下降（）。在其他标志物中，KIM-1 也能够将 LN 与其他组区分开来，而 NGAL、OPN 和 Gal-3 则不能在本队列中区分。 结论：鉴于其能够将 LN 患者与活动期非肾脏和非活动期 SLE 患者区分开来，与肾活检中的活动指数相关，并且在治疗后水平下降，u-Gal-3BP 有望成为一种非侵入性尿液生物标志物，用于帮助检测和监测 SLE 患者的肾脏受累情况，并且应该在更大的队列中进行验证。
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