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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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Hill GS,Karoui KE,Karras A,Mandet C,Van Huyen JD,Nochy D,Bruneval P

doi

10.1038/ki.2010.466

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

635-642

issue

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)54848-5

journal_volume

pub_type

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Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. I. Immunohistochemical studies.