title: miR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis.
abstract: BACKGROUND
  Despite overall improvement in prognosis, 10-30% of patients with lupus nephritis (LN) will develop end-stage renal disease. To date, renal biopsy is still the 'gold standard' test used to predict renal outcome. However, due to its invasive nature, new non-invasive biomarkers are required. Urinary exosomes, microvesicles released by every epithelial cell facing the urinary space, represent an ideal source of markers for renal dysfunction and injury. Here, we sought to evaluate miR-29c expression levels in urinary exosomes as a novel biomarker of renal fibrosis in LN.
  
  
  METHODS
  Urinary exosomes were isolated from 32 samples of patients with biopsy-proven LN, 15 non-lupus chronic kidney diseases and 20 healthy controls. Electronic microscopy and western blot were used to characterize the exosomes. Expression levels of miR-29c were detected by RT-PCR quantitative and correlated with clinical and histological parameters along with the expression levels of Smad2/3, TGF-β and MMP2/9. For comparison, miRNA expression was also evaluated in the urinary pellet.
  
  
  RESULTS
  MiR-29c levels in urinary exosomes showed a negatively strong correlation with the histological chronicity index (r = -0.898, P = 0.001) and glomerular sclerosis (r = -0.555, P = 0.007). No correlation with eGFR and creatinine levels was found. MiR-29c expression levels could predict the degree of chronicity in patients with LN with an area under the curve (AUC) of 0.946 (P < 0.001) and with high sensitivity and specificity (94% and 82%). Smad3 and MMP2 expression in urinary exosomes correlated negatively with miR-29c expression (r = -0.737 and -0.856, respectively). In the urinary pellet, no miR-29c expression was detected; however, upregulation of Smad3 and MMP2 was observed (3.54- and 5.85-fold increase).
  
  
  CONCLUSIONS
  Overall, miR-29c correlated with the degree of renal chronicity but not with renal function, suggesting it could be used as a novel non-invasive marker of early progression to fibrosis in patients with LN.
authors.affiliation: Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall D'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Solé
authors.affiliation: Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall D'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Cortés-Hernández
authors.affiliation: Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall D'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain Department of Renal Pathology, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Felip
authors.affiliation: Department of Renal Pathology, Hospital Universitari Vall D'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vidal
authors.affiliation: Department of Medicine, Systemic Autoimmune Diseases Unit, Hospital Universitari Vall D'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Ordi-Ros
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000235:genetics*; D005260:Female; D005355:Fibrosis / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology*; D008181:Lupus Nephritis / Q000150:complications* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000652:urine*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: biomarker; lupus nephritis; microRNA; renal fibrosis; urinary exosome