# Urinary Lipidomic profile in FSGS: A novel biomarker

> **NIH NIH R03** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $79,500

## Abstract

Focal segmental glomerulosclerosis (FSGS) is the most common glomerular pathology that leads
to progression and end-stage kidney disease during childhood. There is a lack of non-invasive,
reliable biomarkers that predict the diagnosis, prognosis and outcome of FSGS. Furthermore,
FSGS diagnosis can be delayed as most of the patients with nephrotic syndrome do not undergo
kidney biopsies until they have failed steroid therapy. Increased concentrations of circulating lipids
and intracellular lipid deposits is a common finding in FSGS. However how lipid anomalies are
linked to progression remains unsolved. We discovered a distinct urinary lipid metabolite panel in
FSGS that predicted the diagnosis and prognosis of FSGS by untargeted lipidomics analysis.
Patients with FSGS displayed increased urinary concentrations of lysophosphotidycholine (LPC)
and free fatty acids (FFA). We propose that implementation of this phospholipid profile as a
biomarker panel is a powerful tool in prediction of diagnosis and prognosis of FSGS and to monitor
response to treatment. SA-1 of this proposal will further validate the use of phospholipid and FFA
panel by measuring these lipid metabolites in baseline serum and urine samples of patients
collected in a national cohort of patients with FSGS and minimal change disease (MCD)
(NEPTUNE) by targeted lipid analysis. The enrolled patients have completed at least 5 years of
follow-up. We will assess the correlation between clinical outcomes (change in urine protein
excretion and kidney function) and concentrations of the lipid metabolites in patient biosamples
obtained at the entry to NEPTUNE. We will investigate sensitivity, specificity, positive predictive
value, and negative predictive value of lipid biomarkers in diagnosis and prognosis of FSGS. SA-
2 of this proposal, will examine the mechanism of increased urinary LPC and FFA in an animal
model of FSGS. We demonstrated increased activation of cytosolic phospholipase A2 (cPLA2)
enzyme that breaks down membrane phosphotidylcholines to LPC and FFA in podocytes and
tubular epithelial cells in a mouse model of FSGS. In SA-2 our goal is to investigate the role of
cPLA2 in cellular injury and progression of FSGS in Fyn–/–Cd2ap+/– bigenic FSGS mouse model
with cPLA2 gene knock-out. In parallel with mouse experiments, we will use BuffaloMna rats to
investigate cPLA2 expression in this spontaneous FSGS model. We hypothesize that inhibition
of cPLA2 will alleviate cellular injury and progression in FSGS.
In this research proposal our goal is to develop a novel lipid metabolite biomarker panel that will
aid in prediction of diagnosis and prognosis of FSGS. Furthermore, this novel biomarker panel
will improve the way treatment response is monitored. Delineation of the mechanism of lipid
mediated injury will lead to development of novel treatments in FSGS. Our overarching goal is to
improve the care and outcome of FSGS patients by developing novel diagnostic and prognostic
lipid bioma...

## Key facts

- **NIH application ID:** 10218880
- **Project number:** 1R03TR003916-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Elif Erkan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,500
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218880

## Citation

> US National Institutes of Health, RePORTER application 10218880, Urinary Lipidomic profile in FSGS: A novel biomarker (1R03TR003916-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10218880. Licensed CC0.

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