Summary of study ST000939

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000648. The data can be accessed directly via it's Project DOI: 10.21228/M8X38B This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST000939
Study TitlePredicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome using Plasma Metabolomics
Study TypeDiscovery Metabolomics
Study SummaryPaired citrate plasma samples were collected from 27 steroid-sensitive and 14 steroid-resistant nephrotic syndrome participants prior to beginning treatment and after an average of 7 weeks (range 3-19 wks) of treatment with a corticosteroid.
Institute
RTI International
DepartmentDiscovery-Science-Technology
LaboratoryNIH Eastern Regional Comprehensive Metabolomics Resource Core at UNC Chapel Hill (ERCMRC)
Last NameSumner
First NameSusan
Address3040 E. Cornwallis Road, Research Triangle Park, NC 27709, USA
Emailsusan_sumner@unc.edu
Phone704-250-5000
Submit Date2018-03-01
Total Subjects86
Study CommentsFactor Description 1. Treatment Response R = Steroid Resistant; S = Steroid Sensitive; Steroid resistance was defined as failure to enter complete remission after 6-8 weeks of daily oral steroids; Steroid sensitive was defined as clinical remission after 6-8 weeks of daily oral steroids. 2. Draw Number Draw 1 sample, ‘Pre’, was collected at the time of disease presentation before even a single dose of glucocorticoids, and Draw 2 sample, ‘Post’, was collected after 6-10 weeks of Glucocorticoid therapy. 3. Age Age in years at the time of Draw 1, or 'Pre', sample collection Other sample data Weeks difference Time in weeks between draw 1, 'pre', and draw 2, 'post', treatment sample collection Gender M = male; F = female Race self-reported (Native American or Alaskan Native/Asian/Black or African American/Native Hawaiian or Other Pacific Islander/White/More than one race) Ethnicity self-reported (Hispanic or Latino/Not Hispanic or Latino/Unknown)
Raw Data AvailableYes
Raw Data File Type(s)pdata, .temp, .txt, .par, acqu, scon2, etc.
Analysis Type DetailNMR
Release Date2019-03-06
Release Version1
Susan Sumner Susan Sumner
https://dx.doi.org/10.21228/M8X38B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR000648
Project DOI:doi: 10.21228/M8X38B
Project Title:Defining and Predicting Steroid-Resistance in Children with Nephrotic Syndrome by Metabolic Profiling
Project Type:Metabolomics
Project Summary:Nephrotic syndrome (NS) is a very common kidney disease in children. Glucocorticoids (GC) are the primary therapy, but are ineffective in ~20% of children and ~50% of adult cases. Patients with steroid resistant NS (SRNS) fail to enter remission after prolonged oral GC treatment, and are at high risk for GC-induced side effects and progression to end-stage kidney disease. This study aimed to discover markers of steroid resistance that could be potentially used to predict SRNS at presentation, and develop an improved mechanistic definition of pediatric SRNS. Plasma samples were collected from 30 steroid sensitive NS (SSNS) and 15 SRNS patients, and paired samples analyzed which were collected both at disease presentation, prior to any steroid therapy, and after ~7 weeks of daily GC treatment. Broad spectrum 1HNMR data were acquired, binned, and concentration fit. Multivariate analyses and hypothesis testing were used to determine the metabolites that best differentiated the four phenotypic groups. Treatment effects on metabolomics profiles were observed between paired Pre- and Post- treatment SSNS groups, and between Post SSNS and SRNS groups. Metabolites most perturbed by GC treatment included lipoproteins , adipate, pyruvate, alanine, creatine, glucose, tyrosine, valine, and glutamine. Logistic regression using a stepwise variable selection method was used on Pre- samples to model the odds at clinical presentation of SRNS. After controlling for age, the step-wise logistic regression model selected increased glutamine (OR= 1.01; 0.99-1.02 95% CI) as a marker of SRNS. A similar model with children age >3 only, indicated that children with reduced levels of malonate (OR=0.94; 0.89-1.00 95% CI) had an increased odds of SRNS . Thus, malonate concentration may be a potential plasma biomarker for identifying SRNS at initial clinical presentation.
Institute:The Ohio State University;Nationwide Children’s Hospital
Department:Department of Pediatrics and Center for Clinical and Translational Research
Last Name:Smoyer; Agrawal
First Name:William; Shipra
Address:700 Children's Drive, Columbus, OH 43205
Email:William.Smoyer@nationwidechildrens.org and shipra.agrawal@nationwidechildrens.org
Phone:(614) 722-4360
Funding Source:NIH Grants 1UMDK10086601, 1U24DK097193, and 7K01GM109320

Subject:

Subject ID:SU000978
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment Response Gender
SA055817TP2Pool -
SA055818TP1Pool -
SA055819TP3Pool -
SA055820TP4Pool -
SA055821S_41_ASteroid Resistant -
SA055822S_14_BSteroid Resistant F
SA055823S_9_ASteroid Resistant F
SA055824S_9_BSteroid Resistant F
SA055825S_21_ASteroid Resistant F
SA055826S_15_ASteroid Resistant F
SA055827S_17_BSteroid Resistant F
SA055828S_26_BSteroid Resistant F
SA055829S_17_ASteroid Resistant F
SA055830S_20_BSteroid Resistant F
SA055831S_21_BSteroid Resistant F
SA055832S_2_ASteroid Resistant F
SA055833S_2_BSteroid Resistant F
SA055834S_20_ASteroid Resistant F
SA055835S_26_ASteroid Resistant F
SA055836S_43_ASteroid Resistant F
SA055837S_14_ASteroid Resistant F
SA055838S_15_BSteroid Resistant F
SA055839S_43_BSteroid Resistant F
SA055840S_35_BSteroid Resistant M
SA055841S_35_ASteroid Resistant M
SA055842S_40_BSteroid Resistant M
SA055843S_44_BSteroid Resistant M
SA055844S_44_ASteroid Resistant M
SA055845S_3_ASteroid Resistant M
SA055846S_3_BSteroid Resistant M
SA055847S_13_ASteroid Resistant M
SA055848S_40_ASteroid Resistant M
SA055849S_13_BSteroid Resistant M
SA055850S_16_BSteroid Sensitive -
SA055851S_16_ASteroid Sensitive -
SA055852S_33_ASteroid Sensitive F
SA055853S_29_ASteroid Sensitive F
SA055854S_33_BSteroid Sensitive F
SA055855S_29_BSteroid Sensitive F
SA055856S_36_ASteroid Sensitive F
SA055857S_45_ASteroid Sensitive F
SA055858S_38_ASteroid Sensitive F
SA055859S_38_BSteroid Sensitive F
SA055860S_34_ASteroid Sensitive F
SA055861S_34_BSteroid Sensitive F
SA055862S_24_BSteroid Sensitive F
SA055863S_12_ASteroid Sensitive F
SA055864S_12_BSteroid Sensitive F
SA055865S_11_ASteroid Sensitive F
SA055866S_18_ASteroid Sensitive F
SA055867S_19_BSteroid Sensitive F
SA055868S_22_BSteroid Sensitive F
SA055869S_19_ASteroid Sensitive F
SA055870S_10_ASteroid Sensitive F
SA055871S_10_BSteroid Sensitive F
SA055872S_5_ASteroid Sensitive F
SA055873S_5_BSteroid Sensitive F
SA055874S_7_BSteroid Sensitive F
SA055875S_7_ASteroid Sensitive F
SA055876S_8_ASteroid Sensitive F
SA055877S_8_BSteroid Sensitive F
SA055878S_22_ASteroid Sensitive F
SA055879S_18_BSteroid Sensitive F
SA055880S_24_ASteroid Sensitive F
SA055881S_1_BSteroid Sensitive M
SA055882S_27_BSteroid Sensitive M
SA055883S_27_ASteroid Sensitive M
SA055884S_42_BSteroid Sensitive M
SA055885S_42_ASteroid Sensitive M
SA055886S_6_ASteroid Sensitive M
SA055887S_6_BSteroid Sensitive M
SA055888S_1_ASteroid Sensitive M
SA055889S_4_BSteroid Sensitive M
SA055890S_4_ASteroid Sensitive M
SA055891S_25_ASteroid Sensitive M
SA055892S_28_BSteroid Sensitive M
SA055893S_28_ASteroid Sensitive M
SA055894S_25_BSteroid Sensitive M
SA055895S_30_ASteroid Sensitive M
SA055896S_31_BSteroid Sensitive M
SA055897S_31_ASteroid Sensitive M
SA055898S_32_BSteroid Sensitive M
SA055899S_37_BSteroid Sensitive M
SA055900S_37_ASteroid Sensitive M
SA055901S_39_ASteroid Sensitive M
SA055902S_23_ASteroid Sensitive M
SA055903S_39_BSteroid Sensitive M
SA055904S_23_BSteroid Sensitive M
SA055905S_30_BSteroid Sensitive M
SA055906S_32_ASteroid Sensitive M
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Collection:

Collection ID:CO000972
Collection Summary:None
Collection Protocol Comments:Citrate plasma
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR000992
Treatment Summary:None

Sample Preparation:

Sampleprep ID:SP000985
Sampleprep Summary:Study sample aliquots of 180 µL were mixed with 60 µL 0.9% saline solution containing 0.2% NaN3 and 4 mM formate in D2O. A total pool was also created by combining 11 µL aliquots from each study sample, mixed thoroughly, divided into four 180 µL aliquots, and processed identically to study samples. All of the samples were thoroughly mixed on multiple tube vortex mixer for 30 s at 5000 rpm, centrifuged at room temperature and 12,000 rcf for 5 min. The supernatants (200 µL) were stored in a fresh 1.5 mL centrifuge tubes overnight at 4 C, before transfer into pre-labeled 3mm NMR tubes (Bruker-Biospin, Switzerland) on the day of analysis.
Extract Storage:4℃

Analysis:

Analysis ID:AN001540
Laboratory Name:David H. Murdock Research Institute at Kannapolis, NC
Analysis Type:NMR
Software Version:Bruker TopSpin 3.2
Operator Name:Kevin Knagge / Jessica Gooding
Detector Type:NMR
Data Format:1r, fid
Num Factors:7
Num Metabolites:28
Units:mM in NMR Sample

NMR:

NMR ID:NM000119
Analysis ID:AN001540
Instrument Name:Bruker Avance III
Instrument Type:FT-NMR
NMR Experiment Type:1D 1H
Field Frequency Lock:Deuterium
Standard Concentration:1 mM
Spectrometer Frequency:700 MHz
NMR Probe:CRYO QNP
NMR Solvent:D2O
NMR Tube Size:3 mm
Shimming Method:topshim
Pulse Sequence:cpmgpr1d
Water Suppression:Yes
Pulse Width:12.781 us
Power Level:19 W
Receiver Gain:4
Offset Frequency:3294.20 Hz
Chemical Shift Ref Cpd:formate
Temperature:25
Number Of Scans:128
Dummy Scans:4
Acquisition Time:3.892 s
Relaxation Delay:2 s
Spectral Width:12 ppm
Num Data Points Acquired:65536
Real Data Points:65536
Line Broadening:0.5 Hz
Zero Filling:yes
Apodization:Lorentzian
Baseline Correction Method:Polynomial
Chemical Shift Ref Std:Formate
Binned Increment:0.04
Binned Data Excluded Range:water (4.55 – 5.15 ppm) and citrate (2.47-2.565 and 2.61-2.70)
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