The Pathology Lesion Patterns of Podocytopathies: How and why?

Fiammetta Ravaglia,Laura Lasagni,Maria Lucia Angelotti,Letizia De Chiara,Paola Romagnani,Maria Elena Melica

doi:10.3389/fcell.2022.838272

Abstract

Podocytopathies are a group of proteinuric glomerular disorders driven by primary podocyte injury that are associated with a set of lesion patterns observed on kidney biopsy, i.e., minimal changes, focal segmental glomerulosclerosis, diffuse mesangial sclerosis and collapsing glomerulopathy. These unspecific lesion patterns have long been considered as independent disease entities. By contrast, recent evidence from genetics and experimental studies demonstrated that they represent signs of repeated injury and repair attempts. These ongoing processes depend on the type, length, and severity of podocyte injury, as well as on the ability of parietal epithelial cells to drive repair. In this review, we discuss the main pathology patterns of podocytopathies with a focus on the cellular and molecular response of podocytes and parietal epithelial cells.

Highlights

Podocytes are differentiated epithelial cells whose number is determined shortly before birth as nephrogenesis ceases (Bertram et al, 2011)
In the diphtheria toxin (DT) model, 21–40% podocyte depletion showed mesangial expansion, capsular adhesions, focal segmental glomerulosclerosis, mild persistent proteinuria and normal renal function, while more than 40% podocyte depletion showed segmental to global glomerulosclerosis with sustained high-grade proteinuria and reduced renal function (Wharram et al, 2005)
The PEC compartment responds promptly with proliferation but it fails to complete the differentiation process towards mature podocytes. This results in obliteration of Bowman capsule with immature elements further compressing the glomerular tuft that lacks support from external and internal sides (Figure 1 and Table 1). These observations suggest that podocytopathies represent a complex group of disorders of the glomerular epithelial compartment, where the equilibrium between the nature, the length and the severity of podocyte injury as well as the efficiency of the repair response provided by PECs determines the pattern of injury observed at the biopsy as well as renal prognosis

Summary

INTRODUCTION

Podocytes are differentiated epithelial cells whose number is determined shortly before birth as nephrogenesis ceases (Bertram et al, 2011). Pathology of Podocytopathies subset of the glomeruli; 3) diffuse mesangial sclerosis (DMS) characterized by mesangial matrix increase and podocyte hypertrophy; and lastly 4) collapsing glomerulopathy (CG) which presents as collapse of the glomerular capillaries and hyperplasia of parietal epithelial cells (PECs) migrating to the tuft forming “pseudocrescents” (Barisoni et al, 2007) These glomerular histopathological lesion patterns can be collectively viewed as podocytopathies and their progression to chronic kidney disease is related to the amount of podocyte loss (Kopp et al, 2020). The glomerular basement membrane is split and wavy because of zones of subepithelial lucent widening and segmental denudation due to foot process detachment (Charles Jennette et al, 2015)

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Findings

CONCLUSIONS