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Record W2974379499 · doi:10.1016/j.ekir.2019.09.009

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

2019· article· en· W2974379499 on OpenAlexafffund
Shipra Agrawal, Michael L. Merchant, Jiro Kino, Ming Li, Daniel W. Wilkey, Adam E. Gawęda, Michael E. Brier, Melinda A. Chanley, Jessica Gooding, Jon B. Klein, William E. Smoyer, John D. Mahan, Hiren P. Patel, Richard F. Ransom, Cynthia G. Pan, Denis F. Geary, Myra L. Chang, Keisha L. Gibson, Franca M. Iorember, Patrick D. Brophy, Tarak Srivastava, Larry A. Greenbaum

Bibliographic record

VenueKidney International Reports · 2019
Typearticle
Languageen
FieldMedicine
TopicRenal Diseases and Glomerulopathies
Canadian institutionsSickKids FoundationUniversity of Toronto
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesResearch Institute, Nationwide Children's HospitalSchool of Medicine, Emory UniversityHospital for Sick ChildrenWest Virginia UniversityLouisiana State UniversityUniversity of LouisvilleUniversity of North Carolina at Chapel HillNational Institutes of HealthChildren's Mercy HospitalNational Institute on Alcohol Abuse and AlcoholismEmory University
KeywordsMedicineBiomarkerInternal medicineVitamin D-binding proteinNephrotic syndromeEndocrinologyBioinformaticsVitamin D and neurologyBiologyGenetics

Abstract

fetched live from OpenAlex

INTRODUCTION: Nephrotic syndrome (NS) is a kidney disease that affects both children and adults. Glucocorticoids have been the primary therapy for >60 years but are ineffective in approximately 20% of children and approximately 50% of adult patients. Unfortunately, patients with steroid-resistant NS (SRNS; vs. steroid-sensitive NS [SSNS]) are at high risk for both glucocorticoid-induced side effects and disease progression. METHODS: = 86) from 45 patients with NS (30 SSNS and 15 SRNS) obtained at initial disease presentation before glucocorticoid initiation and after approximately 7 weeks of glucocorticoid therapy to identify candidate biomarkers able to either predict SRNS before treatment or define critical molecular pathways/targets regulating steroid resistance. RESULTS: Stepwise logistic regression models identified creatinine concentration and glutamine concentration (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 0.99-1.02) as 2 candidate biomarkers predictive of SRNS, and malonate concentration (OR: 0.94; 95% CI: 0.89-1.00) as a third candidate predictive biomarker using a similar model (only in children >3 years). In addition, paired-sample analyses identified several candidate biomarkers with the potential to identify mechanistic molecular pathways/targets that regulate clinical steroid resistance, including lipoproteins, adipate, pyruvate, creatine, glucose, tyrosine, valine, glutamine, and sn-glycero-3-phosphcholine. CONCLUSION: Metabolomic analyses of serial plasma samples from children with SSNS and SRNS identified elevated creatinine and glutamine concentrations, and reduced malonate concentrations, as auspicious candidate biomarkers to predict SRNS at disease onset in pediatric NS, as well as additional candidate biomarkers with the potential to identify mechanistic molecular pathways that may regulate clinical steroid resistance.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.475

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.250
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations53
Published2019
Admission routes2
Has abstractyes

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