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Pediatric Nephrology
Published in: Pediatric Nephrology 10/2018

01-10-2018 | Original Article

Use of genomic and functional analysis to characterize patients with steroid-resistant nephrotic syndrome

Authors: Thomas M. Kitzler, Nadezda Kachurina, Martin M. Bitzan, Elena Torban, Paul R. Goodyer

Published in: Pediatric Nephrology | Issue 10/2018

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Abstract

Background

Children with genetic causes of steroid-resistant nephrotic syndrome (SRNS) usually do well after renal transplantation, while some with idiopathic SRNS show recurrence due to a putative podocyte-toxic factor. Distinguishing different forms of SRNS based on clinical criteria has been difficult. The aim of our study was to test a novel approach that allows categorization of patients into clinically useful subgroups.

Methods

Seventeen patients with clinically confirmed SRNS were analyzed by next-generation sequencing (NGS) of 37 known SRNS genes and a functional assay of cultured human podocytes, which indirectly tests for toxicity of patients’ sera by evidenced loss of podocyte focal adhesion complex (FAC) number.

Results

We identified a pathogenic mutation in seven patients (41%). Sera from patients with monogenic SRNS caused mild loss of FAC number down to 73% compared to untreated controls, while sera from seven of the remaining ten patients with idiopathic SRNS caused significant FAC number loss to 43% (non-overlapping difference 30%, 95% CI 26–36%, P < 0.001). All patients with recurrent SRNS (n = 4) in the graft showed absence of podocyte gene mutations but significant FAC loss. Three patients had no mutation nor serum podocyte toxicity.

Conclusions

Our approach allowed categorization of patients into three subgroups: (1) patients with monogenic SRNS; (2) patients with idiopathic SRNS and marked serum podocyte toxicity; and (3) patients without identifiable genetic cause nor evidence of serum podocyte toxicity. Post-transplant SRNS recurrence risk appears to be low in groups 1 and 3, but high in group 2.
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Metadata
Title
Use of genomic and functional analysis to characterize patients with steroid-resistant nephrotic syndrome
Authors
Thomas M. Kitzler
Nadezda Kachurina
Martin M. Bitzan
Elena Torban
Paul R. Goodyer
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 10/2018
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-018-3995-2

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