Parietal Epithelial Cell Activation Distinguishes Early Recurrence of FSGS in the Transplant from Minimal Change Disease.
Huma Fatima, Marcus J Moeller, Bart Smeets, Hai-Chung Yang, Agnes B Fogo. Vanderbilt University Medical Center, Nashville, TN; University Hospital of RWTH Aachen University, Germany
Background: Podocyte (PODO) loss is a key factor leading to glomerulosclerosis. Podocytes have limited regenerative capacity. Parietal epithelial cells (PEC) have been proposed as niche stem cells that can transition to podocytes. CD44 is a glycoprotein involved in cell adhesion and migration and is a marker for activated PEC. We investigated whether activated PEC contribute to pathogenesis of recurrent FSGS in transplant.
Design: A total of 25 transplant renal biopsies from 12 patients with recurrent FSGS and four cases of minimal change disease (MCD) were stained for CD44. Of the 25 biopsies of recurrent FSGS, 16 early biopsies had only extensive foot process effacement (FPE) by electron microscopy and no segmental sclerosis and 9 later biopsies had segmental sclerosis. There were a total of 94, 111 and 53 glomeruli in MCD, FPE only and segmental sclerosis cases, respectively. 10 of 53 glomeruli in segmental sclerosis cases had segmental lesions. In each biopsy individual glomeruli were evaluated for the number of epithelial cells staining for CD44 along Bowman's capsule, in anatomical PEC location, and over the glomerular tuft, in anatomical PODO location.
Results: In MCD cases on average 0.05% of glomeruli stained positive for CD44 in PODO location, and 0.01% of glomeruli showed positive staining in PEC location. FPE only cases showed significantly increased positivity in PODO location, on average 0.34 vs 0.06 of glomeruli positive in MCD (p <0.01) and trend for increased CD44 positivity in PEC location, 0.06 vs 0.01 in MCD (p=0.072). In segmental sclerosis cases, there were on average 0.8 positive cells in PODO location in glomeruli without segmental lesion, compared to 4.9 positive cells/ glomerulus in glomeruli with segmental lesions, with most positive cells located in the lesional area. In contrast, average CD44 positive cells in PEC location were similar in glomeruli with (2.8) or without lesions (1.6).
Conclusions: We conclude that there is significantly increased PEC activity in evolving FSGS vs MCD and this may distinguish MCD from early FSGS. Whether the PEC activation is causal and contributes to sclerosis in the pathogenesis of idiopathic FSGS or is a regenerative/ repair response to replace injured podocytes or both, awaits further study.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 275, Wednesday Afternoon