Origin of hyperplastic epithelial cells in idiopathic collapsing glomerulopathy

Aims: Glomerular epithelial cell hypertrophy and hyperplasia are listed as the primary criteria for the diagnosis of collapsing glomerulopathy (CG), a distinct variant of focal segmental glomerulosclerosis, However, the exten t of podocyte phenotypic alterations that occur in CG, and the origin of th e hyperplastic epithelial cells remain to be established, Methods and results: Renal biopsy materials from seven out of three patient s with CG were studied by serial section analysis for immunohistochemistry and electron microscopy, Markers for podocytes (PHM5 and synapto-podin), pa rietal epithelial cells (PECs: cytokeratin) and macrophages (CD68) were use d for the immunohistochemistry. Multiple ultrathin sections from a total of 15 glomeruli, including some from patients with CG, were examined by elect ron microscopy. Glomerular adhesions occurred in 71% of the serially sectio ned glomeruli taken from patients with CG, Hyperplastic epithelial cells we re immunonegative for podocyte markers and CD68, but invariably immunoposit ive for cytokeratin. Electron microscopy revealed that detachment of the po docytes from involved glomerular capillary walls was extensive. Many of the detached podocytes appeared to be necrotic and apoptotic. In contrast, jun ctional complexes of desmosomes and zonula adherens connected hyperplastic epithelial cells to each other Cilia were also often observed. Conclusions: The results of our ultrastructural and immunohistochemical stu dy suggest that the hyperplastic epithelial cells observed in cases of CG a re derived from PECs, Our results raise the possibility that PECs play a ge neral role in covering glomerular tufts from which the podocytes have disap peared.