title: Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies.
abstract: IgA nephropathy (IgAN) often shows lesions morphologically identical with those of focal segmental glomerulosclerosis (FSGS). In order to determine the possible role of FSGS in IgAN lesions, we measured glomerular capsular adhesions, often the first step toward FSGS, in biopsies from 127 patients with IgAN, 100 with lupus nephritis, and 26 with primary FSGS. Capsular adhesions with no lesions in the underlying tuft, consistent with podocyte abnormality or loss, were found regularly in FSGS and IgAN, but infrequently in lupus. Fifteen biopsies of patients with IgAN were studied immunohistochemically using markers for podocytes, Bowman's parietal epithelial cells, proliferating cells, and macrophages. Cytokeratins CK-8 and C2562 differentiated normal podocytes (negative) from parietal epithelial cells (variably positive). There was focal loss of the podocyte markers synaptopodin, glomerular epithelial protein 1 (GLEPP-1), nephrin, and vascular endothelial growth factor (VEGF), particularly at sites of capsular adhesions in otherwise histologically normal glomeruli. Cells displaying the parietal epithelial cell markers PAX2 (paired box gene 2) and the cytokeratins were also positive for the proliferating cell marker, proliferating cell nuclear antigen. These cells gathered at sites of adhesion, and in response to active lesions in the tuft, grew inward along the adhesion onto the tuft, forming a monolayer positive for parietal markers and the podocyte marker Wilms tumor protein-1 (WT-1). These cells deposited a layer of collagen over the sclerosing tuft. Thus, all biopsies of patients with IgAN had changes basically identical to those classically described in FSGS. Hence, our study strongly suggests that podocytopathy of a type similar to that in primary FSGS occurs frequently in IgAN.
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France. Electronic address: garyhillparis@aol.com.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hill
authors.affiliation: INSERM U845, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Khalil El
authors.initials: KE
authors.lastname: Karoui
authors.affiliation: Department of Nephrology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Karras
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mandet
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Jean-Paul Duong
authors.initials: JD
authors.lastname: Van Huyen
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Nochy
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016009:Chi-Square Distribution; D018450:Disease Progression; D004847:Epithelial Cells / Q000737:chemistry; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053533:Keratin-8 / Q000032:analysis; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051762:PAX2 Transcription Factor / Q000032:analysis; D010297:Paris; D050199:Podocytes / Q000737:chemistry; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D025721:WT1 Proteins / Q000032:analysis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D053533:Keratin-8; D051762:PAX2 Transcription Factor; D018809:Proliferating Cell Nuclear Antigen; D025721:WT1 Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C426203:KRT8 protein, human; C497318:PAX2 protein, human