Wanfen Zhang1, Changming Zhang1, Huimei Chen1, Limin Li2, Yuanmao Tu1, Chunbei Liu1, Shaolin Shi1, Ke Zen3, Zhihong Liu4. 1. National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and. 2. Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Nanjing, China. 3. 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. 4. 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.
Abstract
BACKGROUND AND OBJECTIVES: 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. 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.
BACKGROUND AND OBJECTIVES: 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. 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: Sigurd E Delanghe; Marijn M Speeckaert; Hannah Segers; Kaat Desmet; Johan Vande Walle; Steven Van Laecke; Raymond Vanholder; Joris R Delanghe Journal: Clin Biochem Date: 2013-02-04 Impact factor: 3.281
Authors: Hadi Valadi; Karin Ekström; Apostolos Bossios; Margareta Sjöstrand; James J Lee; Jan O Lötvall Journal: Nat Cell Biol Date: 2007-05-07 Impact factor: 28.824
Authors: Hua Zhou; Hiroshi Kajiyama; Takayuki Tsuji; Xuzhen Hu; Asada Leelahavanichkul; Suzanne Vento; Rachel Frank; Jeffrey B Kopp; Howard Trachtman; Robert A Star; Peter S T Yuen Journal: Am J Physiol Renal Physiol Date: 2013-06-12