Proteinuria after injection of human focal segmental glomerulosclerosis factor.

Abstract

Recurrent focal segmental glomerulosclerosis (FSGS) is heralded by proteinuria that may remit after treatment with plasmapheresis or immunoadsorption. Study of recurrent FSGS has been hampered by lack of an animal model that exhibits a pattern of proteinuria that mimics human disease. We have obtained a component of FSGS patient plasma (FSGS factor) that increases glomerular albumin permeability (P(alb)) in vitro and causes transient proteinuria in vivo. Plasma fractions containing FSGS factor and comparable plasma fractions from normal donors were injected into normal male Sprague-Dawley rats. Urinary protein, albumin, and creatinine were measured at various time points. Additionally, plasma samples from test animals were collected after injection and tested for FS activity defined by increased P(alb). Finally, glomeruli were isolated from animals after injection and P(alb) of these glomeruli tested. Proteinuria and albuminuria were increased by 24 hr after injection with FSGS factor, and returned to baseline by 48 hr after injection. Injection with the same fraction of normal plasma had no effect on urinary protein. FSGS factor increased urinary protein in a dose-dependent manner. Serum collected from rats 15 or 60 min after injection with FSGS factor increased P(alb) of glomeruli in vitro, whereas serum collected 3 or more hours after injection had no effect. Glomeruli isolated from rats receiving injections with FSGS factor had increased in vitro P(alb) compared with glomeruli from rats injected with a fraction from normal plasma. We have demonstrated that a single injection of FSGS factor increases P(alb) and, causes transient albuminuria and proteinuria in rats. FS activity in the plasma of recipient rats is also transient. This is the first detailed description of the time course and dose-dependence of proteinuria caused by FSGS factor in an animal model.