Circulating suPAR in two cohorts of primary FSGS

Area of Science:

• Nephrology
• Immunology
• Molecular Biology

Background:

• Soluble urokinase receptor (suPAR) overexpression is linked to FSGS pathology in animal models.
• Previous studies indicated elevated serum suPAR in FSGS patients.

Purpose of the Study:

• To analyze circulating suPAR levels in pediatric and adult patients with biopsy-proven primary FSGS.
• To investigate the association of suPAR levels with clinical parameters, treatment, and genetic factors in FSGS.

Main Methods:

• Analysis of circulating suPAR levels in two independent cohorts: North American FSGS Clinical Trial (CT) and European PodoNet consortium.
• Utilized multiple regression analysis and assessed associations with estimated GFR, sex, treatment, proteinuria, and NPHS2 mutations.

Main Results:

• Elevated suPAR levels were found in 84.3% (CT) and 55.3% (PodoNet) of FSGS patients versus 6% of controls.
• Lower suPAR correlated with higher eGFR, male sex, and mycophenolate mofetil treatment.
• Reduced suPAR levels post-treatment were associated with reduced proteinuria and higher remission odds in the CT cohort.
• NPHS2 mutation carriers showed higher suPAR levels in the PodoNet cohort.

Conclusions:

• Circulating suPAR is elevated in diverse FSGS patient populations and is not a marker of general inflammation.
• Changes in suPAR levels correlate with therapeutic interventions and remission status, supporting its role in FSGS pathogenesis.