Zhao Wenjun, Feng Shi, Wang Yucheng, Wang Cuili, Ren Pingping, Zhang Junjun, Yu Lei, Zhang Chunjiang, Bai Lihua, Chen Ying, Zhou Qin, Qu Lihui, Chen Jianghua, Jiang Hong
Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, China.
Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China.
Kidney Int Rep. 2022 Dec 28;8(3):519-530. doi: 10.1016/j.ekir.2022.12.023. eCollection 2023 Mar.
Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. However, biomarkers for predicting the progression or regression of IgAN remain a clinical challenge. In the present study, we aim to identify promising prognostic markers of IgAN.
Using the cytokine antibody array, we detected serum and urinary levels of 9 common cytokines selected from 23 IgAN-related biomarkers in 32 patients with IgAN and 16 healthy controls. The best biomarkers for distinguishing IgAN patients from healthy controls were identified and confirmed in a multicenter cohort with 222 patients with IgAN and 159 age- and sex-matched healthy controls. Their associations with IgAN progression were further explored in 762 patients with IgAN with a median follow-up of 65 months.
Among the 9 candidate markers, urinary interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) levels were the best for distinguishing patients with IgAN from healthy controls. In the diagnostic cohort, both urinary IL-6 and TGF-β1 levels were elevated in patients with IgAN and showed good discriminatory power, with an area under curve (AUC) of 0.9725 (95% confidence interval: 0.9593-0.9858). Elevated urinary IL-6 level was independently and significantly correlated with the high risk of composite renal outcome (hazard ratio per log-transformed IL-6:1.420 [1.139-1.769]), but no statistical significance was observed between urinary TGF-β1 level and IgAN progression after adjusting for multiple confounders.
Elevated urinary IL-6 and TGF-β1 levels predict the progression of IgAN. Urinary IL-6 is an independent risk factor and a promising noninvasive predictor for IgAN progression.
免疫球蛋白A肾病（IgAN）是全球最常见的肾小球肾炎。然而，用于预测IgAN进展或缓解的生物标志物仍然是一项临床挑战。在本研究中，我们旨在识别有前景的IgAN预后标志物。
我们使用细胞因子抗体阵列，检测了32例IgAN患者和16名健康对照者中从23种IgAN相关生物标志物中选出的9种常见细胞因子的血清和尿液水平。在一个包含222例IgAN患者和159名年龄及性别匹配的健康对照者的多中心队列中，确定并验证了区分IgAN患者与健康对照者的最佳生物标志物。在762例IgAN患者中进一步探讨了它们与IgAN进展的关联，这些患者的中位随访时间为65个月。
在9种候选标志物中，尿液白细胞介素-6（IL-6）和转化生长因子-β1（TGF-β1）水平最能区分IgAN患者与健康对照者。在诊断队列中，IgAN患者的尿液IL-6和TGF-β1水平均升高，且具有良好的鉴别能力，曲线下面积（AUC）为0.9725（95%置信区间：0.9593 - 0.9858）。尿液IL-6水平升高与复合肾脏结局的高风险独立且显著相关（每对数转换后的IL-6的风险比：1.420 [1.139 - 1.769]），但在调整多个混杂因素后，未观察到尿液TGF-β1水平与IgAN进展之间存在统计学意义。
尿液IL-6和TGF-β1水平升高可预测IgAN的进展。尿液IL-6是IgAN进展的独立危险因素和有前景的非侵入性预测指标。
