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Abstract: SA-PO354

A Composite Diagnostic Assay for FSGS

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Mukherjee, Kamalika, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts, United States
  • Alachkar, Nada, Johns Hopkins Hospital, Baltimore, Maryland, United States
  • Gu, Changkyu, Massachusetts General Hospital, Charlestown, Massachusetts, United States
  • Garborcauskas, Garrett, The Massachusetts General Hospital, Charlestown, Massachusetts, United States
  • Stevens, Monica H., Massachusetts General Hospital, Charlestown, Massachusetts, United States
  • Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States
  • Sever, Sanja, Massachusetts General Hospital, Charlestown, Massachusetts, United States
Background

Proteolytic cleavage of the membrane bound urokinase-type plasminogen activator receptor (uPAR) leads to the release of its soluble form suPAR, which has been identified in body fluids. The full-length suPAR undergoes further cleavage and exists in two additional forms: suPARII−III (fragment consists of domain 2 and 3) and suPARI (fragment consists of domain 1). Elevated levels of plasma suPAR and suPAR mediated β3 integrin activation on podocytes have been associated with renal dysfunction and the onset of chronic kidney disease (CKD). However, an increase in suPAR level has also been reported in other disease conditions such as cancer. Therefore, only suPAR level may not be sufficient as a diagnostic parameter for CKD. Here, we sought to develop a composite scoring system, which considers multiple biomarkers, to generate an efficient diagnostic platform for focal segmental glomerulosclerosis (FSGS), a type of CKD.

Methods

Serum samples obtained from healthy individuals and patients with FSGS were analyzed. The levels of full-length suPAR, αvβ3 integrin activation and the presence of suPARII−III fragment were determined. The data were statistically analyzed to develop a biomarker based predictive assay for FSGS.

Results

The majority of FSGS patients exhibited high levels of suPAR and αvβ3 integrin activation on human podocytes in culture. A subset of patients’ serum was positive for the presence of suPARII-III fragment.

Conclusion

The composite diagnostic assay suggests suPAR fragment driven αvβ3 integrin activation in FSGS.

Funding

  • NIDDK Support