Glucocorticosteroid is used for patients with primary nephrotic syndrome. This study aims to identify and validate that biomarkers can be used to predict steroid resistance. Our study contained two stages, discovery and validation stage. In discovery stage, we enrolled 51 minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) patients treated with full dose steroid. Five urinary biomarkers including β2-microglobulin (β2-MG) and α1-microglobulin (α1-MG) were tested and candidates’ biomarkers were selected based on their associations with steroid response. In validation stage, candidates’ biomarkers were validated in two prospectively enrolled cohorts. Validation cohort A included 157 FSGS/MCD patients. Validation cohort B included 59 membranous nephropathy (MN) patients. Patients were classified into response group (RG) or non-response group (NRG) based on their responses to steroid treatment. In discovery stage, higher urinary β2-MG was independently associated with response to corticosteroid treatment in MCD/FSGS patients [OR = 1.89, 95% CI 1.02–3.53] after adjusted by age and gender. In validation cohort A, patients in NRG had a significant higher urinary β2-MG [Ln (β2-MG/uCr): 4.6 ± 1.7 vs 3.2 ± 1.5] compared to patients in RG. We then developed a 3-variable risk score in predicting steroid resistance in FSGS/MCD patients based on the best predictive model including Ln(β2-MG/uCr) [OR = 1.76, 95% CI 1.30–2.37], age [OR = 1.005, 95% CI 0.98–1.03] and pathology [MCD vs FSGS, OR = 0.20, 95% CI 0.09–0.46]. The area under the ROC curves of the risk score in predicting steroid response was 0.80 (95% CI 0.65–0.85). However, no such association was found in MN patients. Our study identified a 3-variable risk score in predicting steroid resistance in patients with FSGS or MCD.

中文翻译：

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预测局灶节段性肾小球硬化或微小病变患者类固醇抵抗的新风险评分。

糖皮质激素用于原发性肾病综合征患者。本研究旨在识别和验证生物标志物可用于预测类固醇耐药性。我们的研究包含两个阶段，发现和验证阶段。在发现阶段，我们招募了 51 名接受全剂量类固醇治疗的微小病变 (MCD) 或局灶节段性肾小球硬化 (FSGS) 患者。测试了包括 β2-微球蛋白 (β2-MG) 和 α1-微球蛋白 (α1-MG) 在内的五种尿液生物标志物，并根据其与类固醇反应的关联选择候选生物标志物。在验证阶段，候选人的生物标志物在两个前瞻性登记的队列中得到验证。验证队列 A 包括 157 名 FSGS/MCD 患者。验证队列 B 包括 59 名膜性肾病 (MN) 患者。根据对类固醇治疗的反应，将患者分为反应组（RG）或无反应组（NRG）。在发现阶段，经年龄和性别调整后，较高的尿 β2-MG 与 MCD/FSGS 患者对皮质类固醇治疗的反应独立相关 [OR = 1.89, 95% CI 1.02-3.53]。在验证队列 A 中，与 RG 患者相比，NRG 患者的尿 β2-MG [Ln (β2-MG/uCr)：4.6 ± 1.7 vs 3.2 ± 1.5] 显着升高。然后，我们根据包括 Ln(β2-MG/uCr) [OR = 1.76, 95% CI 1.30–2.37]、年龄 [OR = 1.005, 95% CI 0.98–1.03] 和病理学 [MCD vs FSGS, OR = 0.20, 95% CI 0.09–0.46]。预测类固醇反应的风险评分的 ROC 曲线下面积为 0.80（95% CI 0.65-0.85）。然而，在 MN 患者中没有发现这种关联。我们的研究确定了预测 FSGS 或 MCD 患者类固醇抵抗的 3 变量风险评分。