Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor

Background: In this study, the profile of urinary EGF excretion (uEGF/uCreat) was mapped in children presenting with prolonged proteinuria or with nephrotic syndrome refractory to or dependent of steroids. We investigated whether uEGF/uCreat could be linked to the underlying biopsy result, taking in...

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Autores principales:	Niels Lodeweyckx, Kristien Wouters, Kristien J. Ledeganck, Dominique Trouet
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	minimal change disease urinary epidermal growth factor ACE-inhibition diagnostic biomarker genetic predisposition Pediatrics RJ1-570
Acceso en línea:	https://doaj.org/article/63b6fe81292044a9a77f2fdab19e248e
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spelling	oai:doaj.org-article:63b6fe81292044a9a77f2fdab19e248e2021-12-01T03:30:08ZBiopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor2296-236010.3389/fped.2021.727954https://doaj.org/article/63b6fe81292044a9a77f2fdab19e248e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fped.2021.727954/fullhttps://doaj.org/toc/2296-2360Background: In this study, the profile of urinary EGF excretion (uEGF/uCreat) was mapped in children presenting with prolonged proteinuria or with nephrotic syndrome refractory to or dependent of steroids. We investigated whether uEGF/uCreat could be linked to the underlying biopsy result, taking into account its response to immunosuppressive medication and to ACE inhibition, as well as genetic predisposition.Methods: Ninety-eight pediatric patients with initial presentation of nephrotic syndrome or prolonged proteinuria were included in this study, along with 49 healthy controls and 20 pediatric Alport patients. All patients had a normal kidney function and were normotensive during the course of the study, whether or not under ACE inhibition. In repeated urine samples, uEGF was measured and concentration was normalized by urine creatinine. In order to compare diagnosis on kidney biopsy, genetic predisposition and response of uEGF/uCreat to immunosuppression and to ACE inhibition, uEGF/uCreat is studied in a linear mixed effects model.Results: Patients with Minimal Change Disease (MCD) showed a significantly different profile of uEGF/uCreat in comparison to healthy children, as well as compared to patients with Focal Segmental Glomerulosclerosis (FSGS) or another glomerulopathy on kidney biopsy. The response of uEGF/uCreat to ACE inhibition was absent in minimal change disease and contrasted with an impressive beneficial effect of ACE inhibition on uEGF/uCreat in FSGS and other proteinuric glomerulopathies. Absence of a genetic predisposition was also associated with a significantly lower uEGF/uCreat.Conclusions: Despite preserved kidney function, children with a proteinuric or nephrotic glomerular disease on kidney biopsy show a significantly lower uEGF/uCreat, indicative of early tubulo-interstitial damage, which appears reversible under ACE inhibition in any underlying glomerulopathy except in minimal change disease. In view of the distinct profile of uEGF/uCreat in minimal change disease compared to other glomerulopathies, and the link between genetic predisposition and uEGF/uCreat, our study suggests that uEGF/uCreat can be a helpful tool to decide on the need for a renal biopsy in order to differentiate minimal change disease from other proteinuric glomerular diseases.Niels LodeweyckxKristien WoutersKristien J. LedeganckDominique TrouetDominique TrouetFrontiers Media S.A.articleminimal change diseaseurinary epidermal growth factorACE-inhibitiondiagnostic biomarkergenetic predispositionPediatricsRJ1-570ENFrontiers in Pediatrics, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	minimal change disease urinary epidermal growth factor ACE-inhibition diagnostic biomarker genetic predisposition Pediatrics RJ1-570
spellingShingle	minimal change disease urinary epidermal growth factor ACE-inhibition diagnostic biomarker genetic predisposition Pediatrics RJ1-570 Niels Lodeweyckx Kristien Wouters Kristien J. Ledeganck Dominique Trouet Dominique Trouet Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
description	Background: In this study, the profile of urinary EGF excretion (uEGF/uCreat) was mapped in children presenting with prolonged proteinuria or with nephrotic syndrome refractory to or dependent of steroids. We investigated whether uEGF/uCreat could be linked to the underlying biopsy result, taking into account its response to immunosuppressive medication and to ACE inhibition, as well as genetic predisposition.Methods: Ninety-eight pediatric patients with initial presentation of nephrotic syndrome or prolonged proteinuria were included in this study, along with 49 healthy controls and 20 pediatric Alport patients. All patients had a normal kidney function and were normotensive during the course of the study, whether or not under ACE inhibition. In repeated urine samples, uEGF was measured and concentration was normalized by urine creatinine. In order to compare diagnosis on kidney biopsy, genetic predisposition and response of uEGF/uCreat to immunosuppression and to ACE inhibition, uEGF/uCreat is studied in a linear mixed effects model.Results: Patients with Minimal Change Disease (MCD) showed a significantly different profile of uEGF/uCreat in comparison to healthy children, as well as compared to patients with Focal Segmental Glomerulosclerosis (FSGS) or another glomerulopathy on kidney biopsy. The response of uEGF/uCreat to ACE inhibition was absent in minimal change disease and contrasted with an impressive beneficial effect of ACE inhibition on uEGF/uCreat in FSGS and other proteinuric glomerulopathies. Absence of a genetic predisposition was also associated with a significantly lower uEGF/uCreat.Conclusions: Despite preserved kidney function, children with a proteinuric or nephrotic glomerular disease on kidney biopsy show a significantly lower uEGF/uCreat, indicative of early tubulo-interstitial damage, which appears reversible under ACE inhibition in any underlying glomerulopathy except in minimal change disease. In view of the distinct profile of uEGF/uCreat in minimal change disease compared to other glomerulopathies, and the link between genetic predisposition and uEGF/uCreat, our study suggests that uEGF/uCreat can be a helpful tool to decide on the need for a renal biopsy in order to differentiate minimal change disease from other proteinuric glomerular diseases.
format	article
author	Niels Lodeweyckx Kristien Wouters Kristien J. Ledeganck Dominique Trouet Dominique Trouet
author_facet	Niels Lodeweyckx Kristien Wouters Kristien J. Ledeganck Dominique Trouet Dominique Trouet
author_sort	Niels Lodeweyckx
title	Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
title_short	Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
title_full	Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
title_fullStr	Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
title_full_unstemmed	Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor
title_sort	biopsy or biomarker? children with minimal change disease have a distinct profile of urinary epidermal growth factor
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/63b6fe81292044a9a77f2fdab19e248e
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Biopsy or Biomarker? Children With Minimal Change Disease Have a Distinct Profile of Urinary Epidermal Growth Factor

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