title: Podocyte injury in pure membranous and proliferative lupus nephritis: distinct underlying mechanisms of proteinuria?
abstract: Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26±0.23 vs. 0.84±0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.
authors.affiliation: 1Division of Rheumatology; Department of Pathology; and Laboratory of Cellular, Genetic, and Molecular Nephrology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: G M
authors.initials: GM
authors.lastname: Rezende
authors.forename: V S
authors.initials: VS
authors.lastname: Viana
authors.forename: D M A C
authors.initials: DM
authors.lastname: Malheiros
authors.forename: E F
authors.initials: EF
authors.lastname: Borba
authors.forename: N A S
authors.initials: NA
authors.lastname: Silva
authors.forename: C
authors.initials: C
authors.lastname: Silva
authors.forename: E P
authors.initials: EP
authors.lastname: Leon
authors.forename: I L
authors.initials: IL
authors.lastname: Noronha
authors.forename: E
authors.initials: E
authors.lastname: Bonfa
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D049109:Cell Proliferation; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008181:Lupus Nephritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D050199:Podocytes / Q000737:chemistry / Q000473:pathology*; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000032:analysis; D013997:Time Factors; D025721:WT1 Proteins / Q000032:analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D008840:Microfilament Proteins; C503967:SYNPO protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human; C113267:nephrin; C516888:PTPRO protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
keywords: Systemic lupus erythematosus; lupus nephritis; podocyte; proteinuria