Development of a novel cell-based assay to diagnose recurrent Focal and Segmental Glomerulosclerosis


Technology: One of the most common glomerular diseases leading to ESRD (end stage renal disease) is FSGS (focal and segmental glomerulosclerosis), whose recurrence (rFSGS) after transplant is estimated to be 20-30% in approximately 1000 FSGS kidney transplant patients each year. With currently no clinically accepted diagnostics to predict rFSGS, an assay that would reliably and reproducibly predict rFSGS would be immensely beneficial in reducing the overall cost of unsuccessful renal transplants. MUSC researchers developed an assay a noninvasive, accurate and economical diagnostic assay to detect rFSGS. This assay is a reporter-based system that utilized multiple promoters from genes that specifically respond to rFSGS patient plasma linked to a reporter (Figure 1).  The estimated sensitivities and specificities were greater than 80% for IL1β and BMF to predict rFSGS compared to FSGS or other nephropathies, and slightly lower for IGFBP3 cell line. Together, the selected promoters result in an incredibly sensitive and specific diagnostic, which additional promoters could be added to at a later date. Further, this assay responded to patient plasma that was frozen for years, indicating the feasibility of this approach in a commercial setup that may require transportation of plasma. Additional advancements have bene made which further optimizes the assay, generating a 3-12 fold response of rFSGS patients to BMS compared to controls. Overall, the concept and approach discussed in this study will serve as the basis for developing similar assays for other nephrotic syndromes including primary FSGS, minimal change disease and membranous nephropathy in native kidneys, whose exact diagnosis currently requires invasive procedure such as renal biopsy. 

Overview: The exact diagnosis of glomerular diseases rests on kidney biopsy findings, an invasive procedure associated with risk of complications and not safe or feasible to perform in a substantial number of patients. Regarding rFSGS, few reports have emerged in the past where claims have been made about the identity of humoral factor/s as the underlying cause of rFSGS, none of them have been clinically confirmed. This has made it difficult to develop a diagnostic assay for rFSGS patients, who continue to suffer from the lack of transplant success, and are relinquished to dialysis. The current standard of care used in the detection of rFSGS is renal biopsy and its average price is approximately $5000. Further, glomerular enlargement assay, antibody and cell-culture based approaches were proposed to diagnose rFSGS, but these assays are time consuming, technically challenging, and involve a panel of antibodies that make them expensive to perform and therefore are unlikely to be adopted commercially. rFSGS leads to unsuccessful kidney transplants, which lead to an enormous cost burden financially and to the resources of the healthcare system. An assay that would reliably and reproducibly predict rFSGS would be immensely beneficial in reducing the overall cost of unsuccessful renal transplants, as these patients could be treated with effective prophylactically and/or perioperative treatment, such as plasmapheresis and/or high-dose cyclosporine and our invention is expected to significantly reduce the cost of testing compared to renal biopsies.


Applications: rFSGS, FSGS, other nephropathies

Advantages: Specific, sensitive, economical, minimally invasive, can be expanded to many nephropathies

Key Words: rFSGS, nephropathies, FSGS, BMF, IL1β, IGFBP3, biopsy, diagnostic, luciferase, assay, cell reporter


Publication: Srivastava et al. (2019) Development of a novel cell-based assay to diagnose recurrent focal segmental glomerulosclerosis patients. Kidney Int, doi: 10.1016/j.kint.2018.10.030.


Inventors: Deepak Nihalani, Michael Janech, Peifeng Deng, Milos Budisavljevic, Ehtesham Arif, Ashish Solanki, Pankaj Srivastava       

Patent Status: US Utility Application filed on 10/9/2019        

MUSC-FRD Technology ID: P1736

Licensing Status:        This technology is available for licensing.

Patent Information:
For Information, Contact:
Scott Davis
Associate Director, Licensing
MUSC Foundation for Research Development
Deepak Nihalani
Pankaj Srivastava
Milos Budisavljevic
Michael Janech
Peifeng Deng
Ashish Solanki
Ehtesham Arif
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