Plasmapheresis Reduces Proteinuria and Serum Capacity to Injure Glomeruli in Patients With Recurrent Focal Glomerulosclerosis

To test the hypothesis that a circulating mediator is associated with recurrent idiopathic focal glomerulosclerosis (FGS), we studied the effect of plasmapheresis on reducing proteinuria in patients with the disease. An in vitro assay measured the capacity of sera before and after plasmapheresis to cause increased albumin permeability (P_albumin) in isolated rat glomeruli. Nine patients (five males aged 2 to 66 years) who underwent plasmapheresis for recurrent FGS were identified. Study variables included age, sex, time from diagnosis of recurrence to first pheresis, glomerular hyalinosis, complications, outcome, and proteinuria before and after plasmapheresis. Rat glomeruli were isolated in medium containing 4 g/dL bovine serum albumin, and P_albumin was determined from the change in glomerular volume in response to an albumin gradient after incubation of the glomeruli in a 1:50 dilution of patient serum. Plasmapheresis reduced proteinuria from a mean of 12 ± 7.46 g/24 hr to 5.1 ± 7.39 g/24 hr (P = 0.03). Six patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had lasting remissions. Preplasmapheresis biopsies in the patients who did not achieve remissions showed both epithelial foot process effacement and glomerular sclerosis. Serum samples were available from four patients for albumin testing in vitro. P_albumin was reduced from a mean of 0.76 ± 0.17 before pheresis to 0.18 ± 0.31 after (P = 0.07). Therefore, the mechanism by which plasmapheresis reduces proteinuria in patients with recurrent FGS involves the decreased capacity of sera from these patients to injure the glomerular permeability barrier. Plasmapheresis is likely to be effective in the therapy of recurrent FGS if the diagnosis is made promptly following the appearance of proteinuria, there is no significant hyalinosis on preplasmapheresis biopsy, and plasmapheresis is initiated immediately.