HISTOPATHOLOGICAL CHARACTERISTICS IN CHILDREN WITH MONOGENIC AND NON-GENETIC STEROID-RESISTANT NEPHROTIC SYNDROME

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https://storage.unitedwebnetwork.com/files/1099/6eae98df18eac242f10de9203c8942ae.pdf

Abstract Title

First Name *

Larisa

Last Name *

Prikhodina

Co-author 1

Svetlana Papizh papijsveta@mail.ru Veltishev Research and Clinical Institute for Pediatrics and Children Surgery of Pirogov Russian National Research Medical University Inherited & Acquired Kidney Diseases Moscow

Co-author 2

Anna Khokhlova annkechina@gmail.com Veltishev Research and Clinical Institute for Pediatrics and Children Surgery of Pirogov Russian National Research Medical University Inherited & Acquired Kidney Diseases Moscow

Co-author 3

Ekaterina Stolyarevich stolyarevich@yandex.ru Moscow City Clinical Hospital № 52 Laboratory of Pathomorphology Moscow

Co-author 4

Patricia Povilaitite povpe@yandex.ru Public Health Agency Laboratory of Experimental Pathomorphology Rostov-on-Don

Co-author 5

Co-author 6

Co-author 7

Co-author 8

Co-author 9

Co-author 10

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Co-author 12

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Introduction

Early onset of steroid-resistant nephrotic syndrome (SRNS) with extrarenal involvement is a hallmark of monogenic SRNS. It remains unclear whether children with monogenic SRNS had specific histopathological features. The aim of the study was to compare histopathological characteristics in children with monogenic and non-genetic SRNS.

Methods

A retrospective single-center study was conducted comparing histopathological features in 39 children (20F/19M) with monogenic (n=19) and non-genetic (n=20) SRNS. The median age at onset of SRNS was 2.7 (IQR: 5.0; 9.0) years. Kidney biopsy with light microscopy (LM) and immunofluorescence (IF) was undertaken in all of patients, electron microscopy (EM) - in 26 (68.4%) individuals. Targeted NGS of 75 SRNS-associated genes was performed in all children. Patients with monogenic SRNS had variants in following genes: NPHS2 (n=4), COL4A3/COL4A5 (n=3), two children each with variants in WT1, LMX1B, C3 and one patient each with variants in ANLN, CRB2, CUBN, LAMA5, LAMB2, SGPL1.

Results

There were no significant differences in the age at onset of SRNS, disease duration before kidney biopsy and baseline eGFR (р>0.05). LM revealed absence any significant differences between children with monogenic and non-genetic SRNS in frequency of FSGS (63.2% vs 65%), rate of global and focal glomerulosclerosis>10% (26.3% vs 20% and 73.7% vs 45%, respectively), tubular atrophy (63.2% vs 50%) and arteriolosclerosis (5.3% vs 5%) (р>0.05). Patients with monogenic SRNS had significantly higher frequency of interstitial fibrosis compared with individuals with non-genetic SRNS (63.2% vs 30%, p=0.038). All children had negative IF. EM showed that patients with monogenic SRNS compared with children with non-genetic SRNS had significantly higher frequency of focal thickening or thinning GBM, or fibrils: 70% vs. 16.7% (p=0.009) without any differences in proportion of diffuse podocyte effacement (66.7% vs 75%), podocyte vacuolization or microvillous transformation (40% vs 66.7%) (р>0.05).

Conclusions

Children with monogenic SRNS had higher frequency of interstitial fibrosis and abnormalities in GBM in comparison with patients with non-genetic SRNS. The absence of specific histopathological features does not allow to differentiate monogenic and non-monogenic forms of SRNS. These findings confirm the need to prioritize genetic testing over kidney biopsy in children with SRNS.

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