title: Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy.
abstract: BACKGROUND
  Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The clinical spectrum of IgAN varies from minor urinary abnormalities to rapidly progressive renal failure. Evaluation of the disease by repeated renal biopsy is not practical due to its invasive procedure. Urinary sediment miRNAs promise to serve as non-invasive biomarkers to assess kidney injury of IgAN.
  
  
  METHODS
  Fifty two biopsy-proven IgAN patients and twenty five healthy controls were enrolled in the study. Urinary sediment miRNAs were extracted. Expressions of miR-34a, miR-205, miR-21, miR-146a and miR-155 were quantified by real-time quantitative polymerase chain reaction (RT-QPCR). The receiver operating characteristic (ROC) curve was used to investigate the value of the miRNAs for predicting diagnosis of IgAN and evaluating histopathological injury. The patients were treated according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and followed up. The roles of miRNAs in reflecting therapeutic efficacy and disease progression were analyzed.
  
  
  RESULTS
  1. The IgAN group had significantly lower urinary miR-34a, miR-205, and miR-155, but higher miR-21 levels than controls. The ROC revealed that urinary miR-34a ≤ 0.047, miR-205 ≤ 0.209, miR-21 ≥ 0.461 and miR-155 ≤ 0.002 could distinguish patients with IgAN from healthy ones. In addition, miR-205 ≤ 0.125 and miR-21 ≥ 0.891 can distinguish IgAN patients with severe tubular atrophy/interstitial fibrosis from those with mild tubular atrophy/interstitial fibrosis. 2. After a mean 15.19 months follow-up, the reduction of proteinuria (g/24 h/year) was positively correlated with baseline urinary miR-21 and inversely correlated with miR-205. The levels of baseline eGFR and miR-205 in the complete remission group were significantly higher than non-complete remission group (p < 0.001; p = 0.018), while proteinuria, miR-21 and miR-146a were lower than non-complete remission group (p = 0.002; p = 0.021; p = 0.009). But multivariate analysis revealed that only baseline eGFR correlated with the remission of IgAN (p = 0.001, OR = 1.042).
  
  
  CONCLUSIONS
  The levels of some urinary sediment miRNAs, especially baseline miR-21 and miR-205, may be used as potential prognostic markers for evaluating the tubulointerstitial damage of IgAN. Furthermore, baseline levels of urinary miRNAs may be predictors of therapeutic efficacy and disease progression.
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China. caiguangyan@sina.com.
authors.forename: Guang-Yan
authors.initials: GY
authors.lastname: Cai
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Duan
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hou
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Zuo-Xiang
authors.initials: ZX
authors.lastname: Li
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Xue-Guang
authors.initials: XG
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Chen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D005260:Female; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000628:therapy* / Q000652:urine*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D009395:Nephritis, Interstitial / Q000175:diagnosis / Q000628:therapy* / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: IgA nephropathy; Therapeutic response; Tubulointerstitial damage; Urinary sediment; miRNAs