Podocyte and endothelial injury in focal segmental glomerulosclerosis: an ultrastructural analysis.

Sekiko Taneda,Kosaku Nitta,Keiko Uchida,Hideaki Oda,Mayuko Ohno,Kazuho Honda

doi:10.1007/s00428-015-1821-9

Abstract

Podocyte injury contributes to the development of focal segmental glomerulosclerosis (FSGS). Endocapillary hypercellularity, which is one of the pathological characteristics of FSGS, suggests that glomerular endothelial injury may also be involved in the pathogenesis of FSGS. In electron micrographs of patients with FSGS (n = 43), we conducted morphometric measurements of foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury and subendothelial widening (SW) of the glomerular basement membrane as a marker of endothelial injury and compared them to those in patients with minimal change nephrotic syndrome (MCNS; n = 11) and control kidney donors (n = 5). Associations between ultrastructural and clinical parameters were analyzed according to the FSGS variants defined by the Columbia classification. FPW was significantly higher in the FSGS group than that in the MCNS and control groups, particularly in the collapsing, tip, and cellular variants of FSGS. Percentage of glomerular basement membrane (GBM) length showing PD and SW was significantly increased in the FSGS group, especially in the collapsing, cellular, and not otherwise specified variants. In FSGS, FPW was inversely correlated with disease duration, but not with proteinuria. Finally, the percentage of GBM length with SW significantly correlated with clinical parameters indicative of poor prognosis, such as lower remission rate and lower estimated glomerular filtration rate at the final observation. Quantitative measurement of podocyte and endothelial injury by electron microscopy might be useful for evaluating histological activity and predicting prognosis in FSGS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00428-015-1821-9) contains supplementary material, which is available to authorized users.

Highlights

Focal segmental glomerulosclerosis (FSGS) is morphologically defined by various histologic patterns of segmental glomerular lesions involving tuft capillary collapse, podocyte hyperplasia and hypertrophy, endocapillary hypercellularity, sclerosis, and hyaline deposits
The significance of this lesion is unknown, but an immunohistochemical study has demonstrated that the glomerular capillaries of the segmental lesion are negative for the endothelial marker CD31 [25], which suggests that segmental lesion with endocapillary hypercellularity may be a sign of endothelial damage and endothelial injury may be involved in the development of FSGS
We morphometrically examined the three parameters of foot process width (FPW), podocyte detachment (PD), and subendothelial widening (SW) ultrastructurally, because a quantitative approach was feasible in the electron micrographs obtained from patients with FSGS

Summary

Introduction

Focal segmental glomerulosclerosis (FSGS) is morphologically defined by various histologic patterns of segmental glomerular lesions involving tuft capillary collapse, podocyte hyperplasia and hypertrophy, endocapillary hypercellularity, sclerosis, and hyaline deposits. The CEL variant is characterized by the presence of endocapillary hypercellularity, intracapillary aggregates of Virchows Arch (2015) 467:449–458 endothelial cells, foam cells, and infiltrating leukocytes, which results in capillary occlusion [3] The significance of this lesion is unknown, but an immunohistochemical study has demonstrated that the glomerular capillaries of the segmental lesion are negative for the endothelial marker CD31 [25], which suggests that segmental lesion with endocapillary hypercellularity may be a sign of endothelial damage and endothelial injury may be involved in the development of FSGS. A few morphometric studies have evaluated podocyte abnormalities in FSGS [5, 31] They focused on foot process effacement by quantitating the foot process width (FPW), but other morphological alterations of podocyte or endothelial damage have rarely been examined.

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