Origin and phenotypic features of hyperplastic epithelial cells in collapsing glomerulopathy.

The characteristic pathological feature of collapsing glomerulopathy (CG) is marked cell hyperplasia and hypertrophy within the glomeruli. The present study investigated the phenotypic alteration of hyperplastic epithelial cells in CG to determine their origin. Renal biopsy specimens from two patients with CG were analyzed by immunohistochemical staining, using markers for podocytes (PHM-5), parietal epithelial cells (PECs; cytokeratin), and cell proliferation (Ki-67). In collapsed glomeruli, hyperplastic and hypertrophic epithelial cells were frequently connected to PECs and collapsed glomerular basement membranes (GBMs). These epithelial cells were more often Ki-67 positive and expressed cytokeratin, whereas PHM-5 was almost invariably negative. Serial section analysis showed that a small number of hyperplastic epithelial cells expressed both PHM-5 and cytokeratin, suggesting phenotypic conversion between podocytes and PECs. Moreover, cytokeratin-positive cells were associated with the sclerotic glomerular segments. Thus, we suggest that the majority of hyperplastic and hypertrophic epithelial cells in CG are of PEC origin. These epithelial features may participate in the development of characteristic tuft collapse and glomerulosclerosis in CG.