Predicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome Using Plasma Proteomics.
biomarkers
nephrotic syndrome
proteomics
steroid resistance
Journal
Kidney international reports
ISSN: 2468-0249
Titre abrégé: Kidney Int Rep
Pays: United States
ID NLM: 101684752
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
31
07
2019
accepted:
09
09
2019
entrez:
11
1
2020
pubmed:
11
1
2020
medline:
11
1
2020
Statut:
epublish
Résumé
Nephrotic syndrome (NS) is a characterized by massive proteinuria, edema, hypoalbuminemia, and dyslipidemia. Glucocorticoids (GCs), the primary therapy for >60 years, are ineffective in approximately 50% of adults and approximately 20% of children. Unfortunately, there are no validated biomarkers able to predict steroid-resistant NS (SRNS) or to define the pathways regulating SRNS. We performed proteomic analyses on paired pediatric NS patient plasma samples obtained both at disease presentation before glucocorticoid initiation and after approximately 7 weeks of GC therapy to identify candidate biomarkers able to either predict steroid resistance before treatment or define critical molecular pathways/targets regulating steroid resistance. Proteomic analyses of 15 paired NS patient samples identified 215 prevalent proteins, including 13 candidate biomarkers that predicted SRNS before GC treatment, and 66 candidate biomarkers that mechanistically differentiated steroid-sensitive NS (SSNS) from SRNS. Ingenuity Pathway Analyses and protein networking pathways approaches further identified proteins and pathways associated with SRNS. Validation using 37 NS patient samples (24 SSNS/13 SRNS) confirmed vitamin D binding protein (VDB) and APOL1 as strong predictive candidate biomarkers for SRNS, and VDB, hemopexin (HPX), adiponectin (ADIPOQ), sex hormone-binding globulin (SHBG), and APOL1 as strong candidate biomarkers to mechanistically distinguish SRNS from SSNS. Logistic regression analysis identified a candidate biomarker panel (VDB, ADIPOQ, and matrix metalloproteinase 2 [MMP-2]) with significant ability to predict SRNS at disease presentation ( Plasma proteomic analyses and immunoblotting of serial samples in childhood NS identified a candidate biomarker panel able to predict SRNS at disease presentation, as well as candidate molecular targets/pathways associated with clinical steroid resistance.
Identifiants
pubmed: 31922062
doi: 10.1016/j.ekir.2019.09.009
pii: S2468-0249(19)31499-8
pmc: PMC6943770
doi:
Types de publication
Journal Article
Langues
eng
Pagination
66-80Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM113226
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA024337
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110077
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK091584
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK095059
Pays : United States
Investigateurs
John Mahan
(J)
Hiren Patel
(H)
Richard F Ransom
(RF)
Cynthia Pan
(C)
Denis F Geary
(DF)
Myra L Chang
(ML)
Keisha L Gibson
(KL)
Franca M Iorember
(FM)
Patrick D Brophy
(PD)
Tarak Srivastava
(T)
Larry A Greenbaum
(LA)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 International Society of Nephrology. Published by Elsevier Inc.
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