title: Evaluation of microRNAs miR-196a, miR-30a-5P, and miR-490 as biomarkers of disease activity among patients with FSGS.
abstract: OBJECTIVE
  This study aimed to identify urinary microRNAs (miRNAs) as biomarkers for FSGS disease activity.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  The levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS disease activity.
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Wanfen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Changming
authors.initials: C
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Huimei
authors.initials: H
authors.lastname: Chen
authors.affiliation: Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Yuanmao
authors.initials: Y
authors.lastname: Tu
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Chunbei
authors.initials: C
authors.lastname: Liu
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Shi
authors.affiliation: 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 liuzhihong@nju.edu.cn kzen@nju.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and liuzhihong@nju.edu.cn kzen@nju.edu.cn.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
mesh_terms: D015415:Biomarkers / Q000652:urine; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000652:urine*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C542543:MIRN196 microRNA, human; C546086:MIRN30b microRNA, human; C574862:MIRN490 microRNA, human; D035683:MicroRNAs
keywords: FSGS; biomarkers; miRNAs; urine
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