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The selective proteinuria observed in patients with focal segmental glomerulosclerosis (FSGS) suggests an abnormal loss of fixed anionic charges on the glomerular capillary wall.In this article, we have studied the putative presence of such factor(s) by using a new in vitro assay to assess glomerular permselectivity by measuring glomerular volume variation (GVV) in isolated glomeruli after hypotonic stress. We randomly tested the serum GVV activity of 10 healthy donors and 143 patients before transplantation. Of the patients, 80 had FSGS, 26 membranous glomerulonephritis, 19 polycystic kidney disease, and 18 malformative uropathies. Moreover, we tested the pre- and posttransplantation serum of 14 patients with recurrence and 14 without recurrence.Serum GVV was significantly higher in patients with FSGS than in those with the other end-stage renal diseases studied(P<0.01) or in healthy donors(P<0.01). However, a wide distribution of serum GVV activity in patients with and without FSGS was observed. Statistically, pregraft GVV values were not predictive of the recurrence of FSGS after transplantation. Moreover, we observed a significant decrease in serum GVV activity after transplantation in patients without recurrence(P<0.01) compared to those who underwent a recurrence.These results reinforce the hypothesis of a circulating factor that alters glomerular albumin permselectivity in FSGS patients. However, the presence of this factor before transplantation did not appear to predict relapse of the disease after transplantation, as recently supported, although its activity seems to be down-regulated after transplantation in patients who do not experience recurrence of the disease.