title: Podocyte-associated mRNA profiles in kidney tissue and in urine of patients with active lupus nephritis.
abstract: OBJECTIVE
  Glomerular deposition of immune complexes and inflammation induce podocyte injury in lupus nephritis (LN). This study hypothesized that the severity of the histological lesions of LN affects podocyte-associated mRNAs profiles in kidney tissue and in urine.
  
  
  METHODS
  Thirty-three patients with LN were grouped according to the presence of mild mesangial (classes I and II) or moderate-to-severe immune complex deposition, proliferation and/or inflammation (classes III, IV and V) in kidney biopsy. Tissue and urine mRNA of nephrin, podocin, podocalyxin, α-actinin-4, transient receptor potential cation channel 6, and of growth factors VEGF-A and TGF-β1 and the transcription factor FOXP3 were measured using real time polymerase chain reaction. These mRNAs were correlated with histological severity of LN, extent of glomerular immune deposits, and tissue infiltrating cells.
  
  
  RESULTS
  Podocyte-associated mRNAs were inhibited in renal tissue of patients with LN irrespective of histological class when compared to controls. However, significantly higher expression of podocyte mRNAs in urine, including those of growth factors and FOXP3, were found in patients with moderate-to-severe nephritis, mostly in class III and IV proliferative forms. The number of invading CD8+ T cells, B cells and macrophages correlated positively with urine podocyte-associated mRNAs. Urine podocyte mRNAs also correlated with proteinuria.
  
  
  CONCLUSIONS
  Inhibition of podocyte-associated mRNAs in kidney tissue suggests that podocyte injury occurs regardless of class severity of LN. Increased urinary excretion of podocyte mRNAs, mostly in patients with moderate-to-severe lesions, may reflect a greater burden of glomerular damage with detachment of podocytes into the urine.
authors.affiliation: Graduate School of Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul Porto Alegre, RS, Brazil.
authors.forename: Mariane
authors.initials: M
authors.lastname: dos Santos
authors.affiliation: Division of Pathology, Hospital de Clínicas de Porto Alegre Porto Alegre, RS, Brazil.
authors.forename: Rafael N
authors.initials: RN
authors.lastname: Bringhenti
authors.affiliation: Graduate School of Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul Porto Alegre, RS, Brazil.
authors.forename: Patrícia G
authors.initials: PG
authors.lastname: Rodrigues
authors.affiliation: Graduate School of Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul Porto Alegre, RS, Brazil.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: do Nascimento
authors.affiliation: Graduate School of Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul Porto Alegre, RS, Brazil.
authors.forename: Sane V
authors.initials: SV
authors.lastname: Pereira
authors.affiliation: Division of Nephrology, Hospital de Clínicas de Porto Alegre Porto Alegre, RS, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Zancan
authors.affiliation: Division of Rheumatology, Hospital de Clínicas de Porto Alegre Porto Alegre, RS, Brazil.
authors.forename: Odirlei A
authors.initials: OA
authors.lastname: Monticielo
authors.affiliation: Division of Rheumatology, Hospital de Clínicas de Porto Alegre Porto Alegre, RS, Brazil.
authors.forename: Andrese A
authors.initials: AA
authors.lastname: Gasparin
authors.affiliation: Division of Nephrology, Irmandade Santa Casa de Misericórdia de Porto Alegre, Universidade Federal de Ciências da Saúde de Porto Alegre Porto Alegre, RS, Brazil.
authors.forename: Waldir P
authors.initials: WP
authors.lastname: de Castro
authors.affiliation: Graduate School of Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul Porto Alegre, RS, Brazil ; Division of Nephrology, Hospital de Clínicas de Porto Alegre Porto Alegre, RS, Brazil.
authors.forename: Francisco V
authors.initials: FV
authors.lastname: Veronese
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006801:Humans; D008181:Lupus Nephritis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000652:urine; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000652:urine; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D016482:Urinalysis; D014556:Urine / Q000166:cytology; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger
keywords: FOXP3; Systemic lupus erythematosus; lupus nephritis; podocin; podocytes; vascular endothelial growth factor