Components of normal serum block the focal segmental glomerulosclerosis factor activity in vitro

Background Sera from some patients with focal segmental glomerulosclerosis (FSGS) increase glomerular albumin permeability (P-alb) in vitro. The hypot hesis that a component of normal serum can protect the glomerular permeabil ity barrier was tested using sera from FSGS patients, normal individuals, a nd several mammalian and avian species. Methods. In most experiments, isolated rat glomeruli were incubated in medi um containing FSGS serum known to increase P-alb in vitro, normal serum, or both active FSGS and normal serum. In other experiments, fractions of norm al serum and serum from other vertebrate species were incubated with active FSGS serum. P-alb was calculated from glomerular capillary expansion in re sponse to an oncotic gradient. To enrich the blocking activity, normal pool ed human plasma was subjected to various biochemical manipulations. Results. Normal human serum prevented the increase in P-alb (active FSGS se ra, 0.77 +/- 0.12; active FSGS sera:normal serum, 1:1 mix, 0.06 +/- 0.30, P < 0.001). Protection diminished as the concentration of normal serum was d ecreased. Specific fractions of human serum, including human albumin and im munoglobulin fractions, were not protective. Blocking activity was present in 80% ammonium sulfate precipitate and certain fractions from size-exclusi on chromatography of normal pooled human plasma. Normal serum from each of the vertebrate species tested also prevented the increase in P-alb Preincub ation with normal serum was protective during subsequent incubation with FS GS serum, but normal serum was not protective after preincubation with FSGS serum. Conclusions. We conclude that a factor or factors in normal serum block the permeability effect of active FSGS sera. This phenomenon may account for v ariability in proteinuria among patients with FSGS and may explain inconsis tent proteinuria following injection of FSGS sera into experimental animals . Characterization of the protective substance(s) and the mechanism by whic h the increase in permeability is blocked may provide insight into the path ogenesis of FSGS.