Expansion of the Parietal Cell Compartment in Collapsing Glomerulopathy.
Miguel F Palma Diaz, Giovanna Giannico, Sharon Phillips, Yu Shyr, Agnes B Fogo, Charles E Alpers, Vivette D D'Agati. Columbia University, New York, NY; University of Washington, Seattle; Vanderbilt University, Nashville, TN
Background: Glomerular epithelial cell hyperplasia and pseudocrescent formation overlying collapsed segments are defining features of collapsing glomerulopathy. The proliferative potential and relative contributions of dedifferentiated podocytes (PODs) versus parietal epithelial cells (PECs) to the glomerular epithelial hyperplasia remain controversial.
Design: We examined 44 biopsies of primary collapsing focal segmental glomerulosclerosis classified by the Columbia classification. Serial paraffin sections were stained with antisera to claudin (an occludens junction protein expressed on PECs and tubular cells), WT-1 (a zinc finger transcription factor expressed by mature PODs) and Ki-67 (proliferation marker). Every glomerulus (including collapsing, NOS and histologically normal phenotypes) in each biopsy was scored for positive cells in lesional vs non-lesional segments and dichotomized for visceral and parietal anatomic locations. Co-localization was investigated by superimposition of serial images.
Results: Histologically normal glomeruli displayed restriction of claudin to PECs lining Bowman's capsule, whereas WT-1 was expressed by visceral PODs and rare parietal PODs, suggesting non-overlapping lineage-specific markers. Variable numbers of claudin+, Ki67+ cells could be identified lining Bowman's capsule in collapsing, NOS and histologically normal glomeruli. There was widespread downregulation or complete loss of WT-1 overlying collapsed segments with swollen PODs. Only rare PODs bearing WT-1 were also Ki-67+. By contrast, most Ki-67+ glomerular epithelial cells were strongly claudin+, indicating predominant expansion of the parietal compartment. Claudin+ cells typically extended out from Bowman's capsule to bridge and overlie the glomerular tuft in acute collapse and more chronic NOS lesions, often mimicking PODs, and formed the majority of cells in the pseudocrescents.
Conclusions: Loss of WT-1 from PODs in collapsing glomerulopathy supports the concept of the dysregulated podocyte phenotype in the pathogenesis of this lesion. PECs can populate the collapsed tuft and comprise the majority of cell cycle-engaged cells in primary collapsing glomerulopathy.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 239, Wednesday Afternoon