Abstract
156 Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by heavy proteinuria, progression to end-stage renal disease, and frequent recurrence in renal allografts. Early recurrence of proteinuria following transplantation and therapeutic effect of plasmapheresis suggest the presence of a causative factor in the circulation of some patients with FSGS. We have documented the presence of permeability activity in sera and plasma of patients with FSGS. Through a series of biochemical manipulations we have succeeded in partially purifying a substance from the plasma of patients with recurrent FSGS which markedly increases albumin permeability in our in vitro assay. The current studies were performed to document that injection of partially purified FSGS factor can cause proteinuria in rats, and that this effect is seen with plasma from different patients. The active fraction of FSGS plasma from Patient 1 (Fpf), 12 mg protein in 1 mL saline, or 12 mg of a comparable fraction of pooled normal human plasma fraction (Npf) was injected intravenously into male Sprague Dawley rats (250-350 g). This amount corresponds to the active protein fraction from about 40 mL of plasma. Urine was collected prior to injection and during 6-12 hour intervals for 2 days. Fpf caused an transient increase in urinary protein in every rat while Npf had no effect. Proteinuria was maximal at 12 hr while serum creatinine was unchanged. Proteinuria, expressed as mg protein/mg creatinine, is shown.TablePlasma from each of three additional patients was subjected to identical biochemical manipulations, and injected into rats in separate experiments. The active fraction from each of these patients caused proteinuria in rats at 12 hours. TableMean arterial pressure in rats injected with Fpf dropped significantly within 3 minutes and returned to normal by 10-15 minutes. Injection with a similar fraction of normal plasma had no effect on mean arterial pressure. In summary, Fpf from each of 4 patients with recurrent FSGS caused transient proteinuria in rats. This finding supports an etiologic role for a circulating factor in human FSGS. The model will be useful for studies of mechanisms of proteinuria and for trials of potential therapeutic agents in FSGS.
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