This study examined six cases of idiopathic
nephrotic syndrome with primary lesions of
focal segmental glomerulosclerosis (FSGS) that relapsed after
renal transplantation. The glomerular lesions comprised the cellular, the collapsing, and the
scar variants of FSGS and showed shedding of large round cells into Bowman's space and within the tubular lumens. Immunohistochemistry and confocal
laser microscopy carried out on kidneys with FSGS relapse disclosed several phenomena. (1) Some podocytes that expressed
podocalyxin, synaptopodin, and glomerular epithelial protein-1 were detached from the tuft and were free in the urinary space. (2) In the cellular variant, most podocytes had lost podocyte-specific
epitopes (
podocalyxin, synaptopodin,
glomerular epithelial protein-1,
Wilm's tumor protein-1,
complement receptor-1, and
vimentin). In the
scar variant, these podocyte markers were absent from cobblestone-like epithelial cells and from pseudotubules. (3) Podocytes had acquired expression of various cytokeratins (CK; identified by the AE1/AE3, C2562, CK22, and AEL-KS2
monoclonal antibodies) that were not found in the podocytes of control glomeruli. Parietal epithelial cells expressed AE1/AE3 CK that were faintly, if ever, found on the parietal epithelial cells of normal glomeruli. (4) Numerous cells located at the periphery of the tuft or free in Bowman's space and within tubular lumens expressed macrophagic
epitopes (identified by PGM1 [CD68], HAM56, and 25F9
monoclonal antibodies). These macrophage-like cells expressed the activation
epitopes HLA-DR and CD16. (5) A number of these cells coexpressed
podocalyxin + AE1/AE3 CK,
podocalyxin + CD68, and CD68 + AE1/AE3. These findings suggest that in primary FSGS relapsing on transplanted kidneys, some "dysregulated" podocytes, occasionally some parietal epithelial cells, and possibly some tubular epithelial cells undergo a process of transdifferentiation. This process of transdifferentiation was especially striking in podocytes that acquired macrophagic and CK
epitopes that are absent from normal adult and fetal podocytes.