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Abstract: FR-OR027

Diagnosing Recurrent FSGS Using a Novel Cell-Based Assay

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Srivastava, Pankaj, MEDICAL UNIVERSITY OF SOUTH CAROLINA, CHARLESTON, South Carolina, United States
  • Arif, Ehtesham, Medical University of South Carolina, Charleston, South Carolina, United States
  • Solanki, Ashish K., Medical University of South Carolina, Charleston, South Carolina, United States
  • Kwon, Kenneth, Medical University of South Carolina, Charleston, South Carolina, United States
  • Janech, Michael G., Medical University of South Carolina, Charleston, South Carolina, United States
  • Nihalani, Deepak, Medical University of South Carolina, Charleston, South Carolina, United States
Background

Here we report a novel human podocyte cell-based assay that will serve as a non-invasive diagnostic clinical tool to detect rFSGS (recurrent focal and segmental glomerulosclerosis), which provides rapid and accurate identification of rFSGS patients. The concepts and approaches demonstrated in this proposal are widely applicable in designing assays for other forms of FSGS ( or ESRD) whose diagnosis and treatment options remains inadequate. This assay is aimed at specifically diagnosing rFSGS to avert the ineffective renal transplant in FSGS patients.

Methods

As a first step, we identified rFSGS responsive genes by mRNA profiling of human podocytes treated with plasma derived from human rFSGS and control patients, which also induced significant alterations to podocyte actin cytoskeleton partially mimicking the disease processes. Two unique candidate genes (proprietary information) based on profiling data from control, non-FSGS and rFSGS patients were selected. In second step, the promoter regions for these genes were cloned into a promoterless reporter vector and transduced into podocytes to generate two stable podocyte cell lines, where expression of reporter was under the control of these promoters. This assay allowed us to measure plasma-induced increase in luminescence in these cells.

Results

Remarkably, both cell lines showed similar results, where only rFSGS patient plasma showed ~2-fold induction, whereas no induction was observed with plasma from other nephropathies including minimal change disease (MCD), membranous glomerulonephritis (MGN) and FSGS (Fig1).

Conclusion

Multiple centers within the country including CureGN and NEPTUNE have been solicited to analyze many rFSGS and non-rFSGS patient plasma using this assay and studies are being planned for conducting clinical trials to utilize its full diagnostic potential.

Funding

  • NIDDK Support