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

Nadia Galal Elhefnawy,Waleed Anwar Abd El Mohsen,Nermine Mohamed Adb Raboh,Esraa Adel Mahmoud,Ola Hassan Nada

doi:10.15171/jnp.2019.24

Nadia Galal Elhefnawy, Waleed Anwar Abd El Mohsen + Show 3 more

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https://doi.org/10.15171/jnp.2019.24

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Journal: Journal of Nephropathology	Publication Date: Aug 11, 2019
Citations: 1	License type: cc-by

Affiliation: Ain Shams University

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.

Highlights

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are two disease entities presented mainly by nephrotic syndrome
Patients and study design This retrospective cohort study included 48 cases; 28cases diagnosed as MCD and 20 cases diagnosed as early FSGS collected from electron microscopy (EM) unit and pathology laboratory at Ain Shams University Specialized hospital in Cairo, during the period from 2011-2016
A statistically significant correlation was detected between claudin-1 expression and the main clinical presentation for MCD at time of biopsy since 63.64% of positive MCD cases were presented by steroid-resistant nephrotic syndrome (SRNS) (P = 0.036; Table 1)

Summary

Introduction

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are two disease entities presented mainly by nephrotic syndrome. Objectives: 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. Around 63.64% of the positive cases were presented by steroid-resistant nephrotic syndrome (SRNS) 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. Primary focal and segmental glomerulosclerosis (FSGS) is responsible for approximately 10%–15% of the cases of nephrotic syndrome (NS) in children and 20%–30% in adults [1]. Biopsy findings of focal tubular atrophy and interstitial fibrosis should prompt a more exhaustive search for unsampled FSGS even with normal looking glomeruli especially in a small biopsy specimen [6]

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