Dystroglycan Patterns in FSGS Variants.
Giovanna Giannico, Sharon Phillips, Yu Shyr, Charles E Alpers, Vivette D D'Agati, Agnes B Fogo. Vanderbilt University, Nashville, TN; University of Washington, Seattle; Columbia University, New York, NY
Background: Background: The dystroglycan (DG) glycoprotein complex links podocytes to the glomerular basement membrane, and through interaction with utrophin interacts with actin in the cytoskeleton. Decreases in αDG have been variably reported in minimal change disease (MCD). αDG contains sialic acid, a necessary component for maintenance of foot processes and the filtration barrier. We investigated whether αDG was altered in variants of FSGS, classified according to the Columbia Classification.
Design: 69 biopsies (5 cellular, 17 collapsing, 3 perihilar, 18 tip, 19 NOS, 7 MCD) with a total of 1289 glomeruli were investigated. Each glomerulus was scored for αDG (0-3 intensity) in the lesional and non-lesional segments in involved glomeruli and in uninvolved glomeruli without segmental lesions.
Results: A mix of lesions were present in biopsies, with 39 glomeruli with cellular lesions, 401 with collapsing lesions, 296 with NOS lesions, 45 with perihilar lesions and 329 with tip lesions. αDG staining was decreased in uninvolved glomeruli in NOS (intensity 2.75), tip (2.79) and minimally decreased in cellular variant cases (2.86), with least staining in uninvolved glomeruli in collapsing glomerulopathy (intensity 2.60). Uninvolved glomeruli showed unaltered αDG in biopsies with perihilar FSGS and in MCD (3.00). Segmental lesions showed nearly absent staining in collapsing glomerulopathy (0.12), with similar low level staining in NOS lesions, and slightly more staining in tip lesional areas (1.00).
Conclusions: αDG staining is decreased in lesional areas of segmental sclerosis, and particularly decreased even in uninvolved segments of glomeruli in collapsing glomerulopathy. We speculate that this may reflect dedifferentiation of podocytes. Furthermore, these findings indicate that decreased dystroglycan may not be specifically or uniquely related to the podocyte perturbations underlying minimal change disease.
Category: Kidney (does not include tumors)
Monday, February 28, 2011 2:00 PM
Platform Session: Section H, Monday Afternoon