Hypertension-Associated Nephrosclerosis: Does the Activation of Parietal Epithelial Cells (PECs) Differ between African Americans and Caucasians?
M Olatokunboh Odubanjo, Bart Smeets, Marcus J Moeller, Agnes B Fogo. Vanderbilt University Medical Center, Nashville, TN; University Hospital of RWTH, Aachen University, Germany
Background: Loss of podocytes is critical for progressive glomerulosclerosis. Parietal epithelial cells (PECs) may act as stem cells that replenish podocytes. Our aim was to determine the extent to which PECs are activated following hypertension-associated injury in African Americans (AA) and Caucasians (C).
Design: Activated PECs were identified by CD44 staining. We scored activated PECs in anatomical parietal and podocyte locations in glomeruli without lesions and glomeruli with segmental sclerosis (SS) and/or adhesions, and the total number of activated PECs was quantified for globally sclerosed (GS) glomeruli.
Results: A total of 352 glomeruli from 31 biopsies were analyzed. 209 glomeruli showed no lesions (50 AA, 159 C), 110 (73 AA, 37 C) showed global sclerosis, 12 (9 AA, 3 C) showed SS and/or adhesions, 19 (10 AA, 9 C) showed periglomerular fibrosis, and 2 (both AA) showed extracapillary proliferation with no GBM breaks or fibrinoid necrosis. The distribution of glomerular lesions differed between AA and C, with glomeruli without lesions being more commonly seen in C, and GS and SS being more common in AA.
Activated PECs were detected in 21 glomeruli, 14 AA and 7 C (8 glomeruli without lesions: 5 AA and 3 C; 4 with GS: 3 AA and 1 C; 4 with SS and or adhesions: all AA; 3 with periglomerular fibrosis: all C; and 2 with extracapillary proliferation: both AA).
There was an average of 7.2 CD44+ cells in parietal location/ glomerulus in AA versus 1.7/ glomerulus in C.
In 4 of the 12 glomeruli with SS and/or adhesions, CD44+ cells were most common in a parietal location and more commonly, away from the lesion than adjacent to the lesion (4 glomeruli, on average 7.25/glomerulus, 6 in parietal location (1 in the lesion and 5 in the non-lesion area) and 1.25 in podocyte location (P value < 0.001 for lesion versus non-lesion area).
Conclusions: Activated PECs were present more commonly in AA than C, even in glomeruli without sclerosing lesions. This supports the possibility that abnormalities in the differentiation and regulation of the glomerular epithelial cell population could contribute to the pathogenesis of the glomerular scarring in arterionephrosclerosis. Whether these activated PECs contribute to sclerosis or represent regenerative repair responses awaits further study.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 260, Wednesday Afternoon