Circulating Permeability Factors in Primary Focal Segmental Glomerulosclerosis: A Review of Proposed Candidates
Table 1
Circulating permeability factors in primary FSGS: summary of proposed candidates.
Circulating factor
Molecular weight (kDa)
Experimental findings
Clinical data for FSGS and CKD
suPAR
25–50
Administration of suPAR caused albuminuria in uPAR −/− mice [46], however not in WT mice [41, 59] Activation of podocytic -integrin leading to cytoskeletal rearrangement [46] Decrease of nephrin expression via suppression of WT-1 [57]
suPAR levels are inversely correlated with eGFR, no discrimination of primary FSGS to other proteinuric diseases [41, 42, 44, 49, 50] suPAR seems to be a microinflammatory marker in FSGS [40] suPAR predicts CKD in a cardiovascular cohort [45] Significance of suPAR levels as a biomarker for FSGS in patients with preserved renal function unclear [53]
CLCF-1
22
Binds to galactose columns [18, 61, 65] and galactose blocked increase in glomerular permeability by FSGS sera [65] Administration of CLCF-1 increases glomerular permeability and proteinuria in mice [60] Decreases nephrin expression and disrupts the podocytic cytoskeleton [60] Inhibitors of the Jak/Stat3 pathway abolish CLCF-1 and FSGS sera effects [61]
Concentration of CLCF-1 in FSGS patients up to 100-fold higher than in controls, however available assay too insensitive at the moment [60] Current data do not support therapy of FSGS patients with galactose [64] Due to measurement difficulties not tested in FSGS cohorts yet
CD40 autoantibodies
150
Expressed in glomeruli from FSGS patients [58] Disrupt podocyte actin cytoskeleton [58] Injection of CD40 autoantibodies leads to albuminuria only if recombinant suPAR is coadministered [58] Administration of CD40 autoantibodies does not increase glomerular permeability in CD40 −/− mice [58]
Identified in autoantibody panel from sera of patients with recurrent FSGS [58]
