Predicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome Using Plasma Proteomics.

Autor:	Agrawal S; The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.; The Ohio State University, Columbus, Ohio, USA., Merchant ML; Kidney Disease Program, University of Louisville, Louisville, Kentucky, USA., Kino J; The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA., Li M; Kidney Disease Program, University of Louisville, Louisville, Kentucky, USA., Wilkey DW; Kidney Disease Program, University of Louisville, Louisville, Kentucky, USA., Gaweda AE; Kidney Disease Program, University of Louisville, Louisville, Kentucky, USA., Brier ME; Kidney Disease Program, University of Louisville, Louisville, Kentucky, USA., Chanley MA; The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA., Gooding JR; National Institutes of Health Eastern Regional Comprehensive Metabolomics Resource Core at UNC, Chapel Hill, North Carolina, USA.; Discovery, Science and Technology, RTI International, Research Triangle Park, North Carolina, USA., Sumner SJ; National Institutes of Health Eastern Regional Comprehensive Metabolomics Resource Core at UNC, Chapel Hill, North Carolina, USA.; Nutrition Research Institute, University of North Carolina, Chapel Hill, North Carolina, USA., Klein JB; Kidney Disease Program, University of Louisville, Louisville, Kentucky, USA.; Robley Rex VA Medical Center, Louisville, Kentucky, USA., Smoyer WE; The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.; The Ohio State University, Columbus, Ohio, USA.
Jazyk:	angličtina
Zdroj:	Kidney international reports [Kidney Int Rep] 2019 Sep 19; Vol. 5 (1), pp. 66-80. Date of Electronic Publication: 2019 Sep 19 (Print Publication: 2020).
DOI:	10.1016/j.ekir.2019.09.009
Abstrakt:	Introduction: 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. Methods: 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. Results: 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 ( P  = 0.003; area under the receiver operating characteristic curve = 0.78). Conclusion: 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. (© 2019 International Society of Nephrology. Published by Elsevier Inc.)
Databáze:	MEDLINE
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