Zhang Wanfen, Zhang Changming, Chen Huimei, Li Limin, Tu Yuanmao, Liu Chunbei, Shi Shaolin, Zen Ke, Liu Zhihong
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, China.
Clin J Am Soc Nephrol. 2014 Sep 5;9(9):1545-52. doi: 10.2215/CJN.11561113. Epub 2014 Aug 8.
This study aimed to identify urinary microRNAs (miRNAs) as biomarkers for FSGS disease activity.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Candidate urinary miRNAs were identified in pooled urine samples from patients with active FSGS (FSGS-A) and FSGS in remission (FSGS-CR), and were then validated using individual samples. Their levels were compared both under different treatment responses in a prospective study of FSGS and in patients with different membranous nephropathy (MN) and diabetic nephropathy (DN) disease activity. The prediction of these miRNAs for treatment responses was further analyzed in both retrospective and prospective cohorts of patients with FSGS.
All 54 miRNAs were included as candidate biomarkers, including those with high levels in patients with FSGS-A (n=9) under the TaqMan Low Density Array as well as those with conserved expression in kidneys and involved in immune response. TaqMan probe-based quantitative RT-PCR confirmed the higher levels of four miRNAs in patients with FSGS-A in two independent cohorts (n=18 and n=80). Urinary miR-196a, miR-30a-5p, and miR-490 discriminated FSGS-A from FSGS-CR, with an area under the curve of ≥ 0.80. After steroid treatment, their levels were lower in steroid-responsive patients with FSGS (all P<0.001), but were unchanged in steroid-resistant patients. The levels of miRNAs were similar between active MN and MN in remission as well as active DN and incipient DN (all P>0.05). Urinary miR-30a-5p marginally predicted the response to steroid treatment in patients with FSGS-A, with an area under the curve of 0.63 (P=0.03).
The levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS disease activity.
本研究旨在鉴定尿微小RNA（miRNA）作为局灶节段性肾小球硬化（FSGS）疾病活动的生物标志物。
设计、地点、参与者及测量方法：在活动性FSGS患者（FSGS-A）和缓解期FSGS患者（FSGS-CR）的混合尿液样本中鉴定候选尿miRNA，然后使用个体样本进行验证。在FSGS的前瞻性研究以及不同膜性肾病（MN）和糖尿病肾病（DN）疾病活动的患者中，比较了它们在不同治疗反应下的水平。在FSGS患者的回顾性和前瞻性队列中进一步分析了这些miRNA对治疗反应的预测情况。
共纳入54种miRNA作为候选生物标志物，包括在TaqMan低密度阵列中FSGS-A患者（n = 9）中水平较高的那些，以及在肾脏中表达保守且参与免疫反应的那些。基于TaqMan探针的定量逆转录聚合酶链反应（RT-PCR）在两个独立队列（n = 18和n = 80）中证实了FSGS-A患者中四种miRNA的水平较高。尿miR-196a、miR-30a-5p和miR-490可区分FSGS-A和FSGS-CR，曲线下面积≥0.80。类固醇治疗后，FSGS类固醇反应性患者中它们的水平较低（均P<0.001），但在类固醇抵抗性患者中无变化。活动性MN与缓解期MN以及活动性DN与早期DN之间的miRNA水平相似（均P>0.05）。尿miR-30a-5p对FSGS-A患者的类固醇治疗反应有一定的预测作用，曲线下面积为0.63（P = 0.03）。
尿miR-196a、miR-30a-5p和miR-490的水平与FSGS疾病活动相关。
