# Integrating Proteomics and Metabolomics to Understand Pediatric Glomerular Disease Pathophysiology and Prognosis

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $345,860

## Abstract

Abstract/Project Summary
 Glomerular disease is the third leading cause of end stage kidney disease in the US, with its related health
care costs estimated at $4.1 billion annually. Immunosuppressive (IS) drugs are the primary therapies for
most glomerular diseases, but ~20-50% of patients fail to achieve a remission. Unfortunately, in the absence of
biomarkers to predict treatment responsiveness, many patients receive prolonged yet ineffective IS therapy,
leaving them at high risk for both toxic side effects and disease progression. Since the prognostic factors and
specific molecular pathways that are the most critical regulators of the various glomerular diseases are not yet
known, there is an urgent need to develop strategies to prevent drug-induced toxicity, and to identify more
targeted and effective treatments for glomerular disease. Our long-term goal is to identify prognostic
biomarkers and molecular pathways that regulate glomerular injury, and use this knowledge to develop
predictive biomarkers and more targeted treatments for glomerular disease. The specific objective of this
proposal is to identify diagnostic and predictive biomarkers and novel molecular pathways/targets for each of
the four CureGN glomerular diseases by integrating state-of-the-art proteomic and metabolomic analyses of
serial plasma samples from pediatric glomerular disease patients. Based on this, we hypothesize that
integrated proteomic and metabolomic analyses of serial clinically and histologically
phenotyped pediatric plasma samples will identify novel biomarkers that predict treatment
responsiveness, as well as molecular targets for targeted glomerular disease treatments.
CureGN is a prospective observational study to clinically phenotype and collect serial blood and urine samples
from 2,400 children and adults with four of the most common types of glomerular disease: MCNS, FSGS, MN,
and IgAN. The rationale for this proposal is that integrating proteomic and metabolomic analyses of serial
clinically and histologically phenotyped pediatric plasma samples will enable identification and validation of
novel biomarkers that can predict glomerular disease treatment responsiveness, as well as novel molecular
targets for future treatments. To test our hypothesis, we propose the following Specific Aims: 1) To compare
sequential pediatric plasma proteomic and metabolomic signatures to identify predictive biomarkers, and to
differentiate molecular pathways that are distinctive or common among all four CureGN glomerular diseases,
2) To integrate proteomic and metabolomic data to identify combined predictive biomarkers, and to
differentiate molecular pathways that are distinctive or common among all four CureGN glomerular diseases,
and 3) To validate candidate biomarkers in independent CureGN pediatric samples. These studies will apply a
state-of-the-art integrated proteomic and metabolomic systems biology approach to a large cohort of
phenotyped pediatric plasma samples to...

## Key facts

- **NIH application ID:** 10020399
- **Project number:** 5R01DK110077-05
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Jon Klein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,860
- **Award type:** 5
- **Project period:** 2016-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020399

## Citation

> US National Institutes of Health, RePORTER application 10020399, Integrating Proteomics and Metabolomics to Understand Pediatric Glomerular Disease Pathophysiology and Prognosis (5R01DK110077-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10020399. Licensed CC0.

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