# Integrative Molecular Epidemiology Approach to Identify Nephrotic Syndrome Subgroups

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $169,560

## Abstract

ABSTRACT
Although patients with Nephrotic Syndrome (NS) present with shared clinical signs and symptoms (proteinuria,
hypoalbuminemia, hyperlipidemia and edema), there is dramatic variability in prognosis and response to
therapy, frustrating patients, families and their clinicians. Even within the histopathologic categories used in
the current diagnostic approach (e.g. minimal change disease, focal segmental glomerulosclerosis), there is
dramatic variability in disease progression and response to therapy, highlighting the underlying biological
heterogeneity within the groups. Small studies with broad, clinical patient inclusion criteria have demonstrated
that a subset of patients respond well to anti-TNF therapy, but accurate pre-treatment response of those
individuals is not possible based on routine clinical parameters.
This project will leverage the Nephrotic Syndrome Study Network (NEPTUNE) cohort study, a multi-center
prospective study of 600 patients with FSGS, MCD and MN with rich clinical data, kidney biopsy tissue and
gene expression profiles. This study will leverage the kidney tissue gene expression data to identify a
subgroup of patients with TNF-alpha pathway activation, assess associated clinical outcomes and identify non-
molecular predictors of the subgroup. The aims are:
 Aim 1: To identify a subgroup of Nephrotic Syndrome patients with homogeneous activation of the
 TNF-alpha transcriptional pathway.
 Aim 2: To compare molecular subgroups with conventional clinical-pathologic classification in
 clinical outcome prediction.
 Aim 3: To identify non-invasive markers (e.g. demographics, blood and urine markers), standard
 pathology features and novel pathologic biopsy descriptors associated with the TNF-alpha
subgroup.
To accomplish this project, the applicant will pursue formal training in systems biology, genetic epidemiology
and bioinformatics. She will be mentored by a multi-disciplinary team with expertise in systems biology,
epidemiology and bioinformatics. The long term objective is to improve the clinical care of patients with
Nephrotic Syndrome by improved understanding of the underlying biology, identifying novel biomarkers and
potential therapeutic targets for future validation in animal models and mechanistic-based interventional clinical
trials.

## Key facts

- **NIH application ID:** 10153763
- **Project number:** 5K08DK115891-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Laura H Mariani
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $169,560
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153763

## Citation

> US National Institutes of Health, RePORTER application 10153763, Integrative Molecular Epidemiology Approach to Identify Nephrotic Syndrome Subgroups (5K08DK115891-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153763. Licensed CC0.

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