# Clinical Assessment of a novel non-invasive assay for diagnosing recurrent focal and segmental glomerulosclerosis

> **NIH NIH R03** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $74,750

## Abstract

The primary goal of this R03 proposal is to develop a novel cell-based assay that will serve as a non-invasive
diagnostic clinical tool to detect a rare form of glomerular disease commonly known as recurrent focal and
segmental glomerulosclerosis (rFSGS). Diagnosing glomerular diseases accurately and in timely fashion is key
to developing a successful treatment plan and thereby prevent their progression to ESRD (end stage renal
disease). However, their successful diagnosis remains challenging due to the complex procedures employed,
which include, invasive renal biopsy followed by immunostaining and ultrastructural analysis. Thus, there is a
compelling need to develop simplified procedures to detect glomerular disease patients with high accuracy and
efficiency. Importantly, our long-term goal is to extend this concept to develop assays for other glomerular
diseases and therefore, reduce or eliminate the need for renal biopsies. Although there are multiple etiologies
for FSGS, dysfunction of podocytes leading to cell death and proteinuria are primary outcomes of all forms of
FSGS. In this study, we demonstrate the development of an assay that specifically diagnosed rFSGS patients
in which, FSGS recurs following renal transplant within hours to weeks and affects more than a third of FSGS
patients (thus classifying it as a rare disorder based on the National Organization of Rare Disorders). Therefore,
the timely diagnosis of rFSGS patients will encourage clinicians to execute preemptive procedures and prevent
ineffective renal transplants that are destined to fail. Since FSGS targets podocyte damage and death, our unique
approach involved mRNA profiling of cultured podocytes treated with rFSGS patient plasma to reveal
upregulated genes involved in cellular damage. Therefore,, we selected three proapoptotic candidate rFSGS
responsive genes IL1-β, BMF, and IGFBP3 that were specifically elevated in rFSGS patient plasma treated
podocytes, their promoter regions were identified and cloned into a luciferase-based reporter vector and
transfected into podocytes/HEK293/Cos7 cells to generate stable cell lines. Strikingly, when these cell lines were
exposed to plasma from rFSGS patients, increased reporter activity was noted; in contrast, no reporter activity
was noted with all the other glomerular disease patients tested. Remarkably, the statistical analysis showed
more than 80% specificity in detecting rFSGS patients. This concept was recently accepted for publication in a
premier kidney journal (Kidney International, In Press). To determine the clinical effectiveness of this assay, in
the Specific Aim 1, we will conduct the clinical validation of constructed cell lines by measuring their responses
towards plasma from various nephropathy patients. Several rFSGS and non-rFSGS patients are being recruited
through various indigenous and collaborative efforts to power this study. Once developed, this assay will form
the basis for conducting worldwide large-scale...

## Key facts

- **NIH application ID:** 9980519
- **Project number:** 5R03TR003038-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Ehtesham Arif
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,750
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980519

## Citation

> US National Institutes of Health, RePORTER application 9980519, Clinical Assessment of a novel non-invasive assay for diagnosing recurrent focal and segmental glomerulosclerosis (5R03TR003038-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9980519. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*