Potential role of Claudin-1 immunohistochemical expression and ultrastructural changes in detecting early focal segmental glomerulosclerosis 

Abstract

Background: Focal segmental glomerulosclerosis (FSGS) and Minimal change disease (MCD) are two disease entities presented mainly by nephrotic syndrome. While 95% of MCD cases showed complete remission on steroid therapy, 50% of FSGS cases progress to end stage renal disease. Early sclerotic lesions in FSGS can be missed in routine H&E examination. Objective: To differentiate early FSGS from MCD by detection of activated parietal epithelial cells (PECs) in early glomerular sclerotic lesions using Claudin-1 immunohistochemical (IHC) staining and by examining podocyte ultrastructural changes. Materials and Methods: This retrospective study included 28 cases diagnosed as MCD and 20 cases diagnosed as early FSGS.  Clinicopathologic data collection, claudin-1 IHC staining and reviewing ultrastructural changes were performed and the results were statistically analyzed. Results: A statistically significant correlation was detected between claudin-1 expression and the initial diagnosis of the studied groups (P=0.005). Claudin-1 was expressed in a visceral location in (39.28%) of the biopsies initially diagnosed as MCD thus were reevaluated as early FSGS lesions. 63.64% of these positive cases were presented by steroid resistant nephrotic syndrome and 63.6% of which showed some ultrastructural changes of FSGS in podocytes including abnormalities in mitochondrial shapes, endoplasmic reticulum changes and a decreased number of autophagic vacuoles. Conclusion: Claudin-1 is a novel diagnostic marker that can differentiate between confusing cases of early FSGS versus MCD. Defective autophagy plays a role in the pathogenesis of FSGS. 

Keywords: Claudin-1 immunohistochemistry, Focal segmental glomerulosclerosis, Minimal change disease, Parietal epithelial cells, ultrastructural changes, defective autophagy