High levels of circulating soluble urokinase plasminogen activator receptor (suPAR) were shown linked to the kidney disease focal segmental glomerulosclerosis (FSGS). Two adult and child cohorts, North American and European, of FSGS patients were studied.
SuPAR is one of many innate immune system activation markers. It is usually found in higher levels when the body is fighting off infection.
Of 164 patients with biopsy-proven FSGS, 69.8% were found to have elevated suPAR between the two cohorts. This was compared to 6% of control participants who had elevated suPAR (P<0.0001). Elevated levels of suPAR were defined as 3,000 pg/mL or higher.
Further analysis was done to test the levels of suPAR when treating with either mycophenolate mofetil or cyclosporine A, two immunosuppressants. The patients of the U.S. cohort were treated with either drug and results showed decreased suPAR with the first drug and raised levels with the second (P<0.05). The European cohort of patients showed significant response only to mycophenolate mofetil, with lower suPAR levels (P<0.05). These correlative suPAR levels may be due to the body detecting the FSGS scar tissue as foreign and raising an immune response against it.
Finally, a 10% decrease of suPAR correlated with a 44% increased chance of complete remission from FSGS (P<0.05).
Taken together, these results show that suPAR levels may be directly correlated with FSGS risk. FSGS may be able to be treated by lowering circulating suPAR. Only further tests will tell.
Changli Wei, Howard Trachtman, Jing Li, Chuanhui Dong, Aaron L. Friedman, Jennifer J. Gassman, June L. McMahan, Milena Radeva, Karsten M. Heil, Agnes Trautmann, Ali Anarat, Sevinc Emre, Gian M. Ghiggeri, Fatih Ozaltin, Dieter Haffner, Debbie S. Gipson, Frederick Kaskel, Dagmar-Christiane Fischer, Franz Schaefer, Jochen Reiser and the PodoNet and FSGS CT Study Consortia. 2012. Circulating suPAR in Two Cohorts of Primary FSGS. Journal of the American Society of Nephrology.