HDCN Article Review/Hyperlink

Savin VJ, Sharma R, Sharma M, McCarthy ET, et al

Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis

N Engl J Med (Apr) 334:878-883 1996

Savin et al measured the ability of serum extracts from patients with proteinuria to induce hyperpermeability to albumin in isolated rat glomeruli. These glomeruli were first exposed to patient serum, and then to an albumin containing solution. The normal response is for the glomeruli to swell due to the oncotic gradient. Decreased swelling means that the glomeruli have become hyperpermeable to albumin. The question asked was whether or not patients with FSGS have a circulating factor present in the serum which somehow induced glomerular hyperpermeability to albumin.

Sera from 100 patients with focal segmental glomerulosclerosis (FSGS) was evaluated, compared to sera from 31 patients with other renal disease and nine normal subjects. Sera from patients with FSGS who had not been transplanted did not induce glomerular hyperpermeability. Nor did sera from transplanted FSGS patients in whom there was no recurrence. The striking finding was a markedly increased glomerular hyperpermeability activity in sera from 33 patients who had recurrence of disease after transplantation. There was a clear correlation between permeability activity and percent of patients who had recurrent disease. Six of the seven patients with sera having permeability activity greater than or equal to 0.50 had recurrent FSGS while only four of 19 patients with activity less than .50 had recurrence after transplantation. Seven patients underwent plasmapheresis following recurrent FSGS with significant falls in the levels of permeability activity in their sera. In the patients treated with plasmapheresis, there was a concomitant marked decrease in the urinary protein/creatinine ratio.

Column elution of an active fractionated precipitate from plasmapheresis fluid in patients with recurrent FSGS and high levels of permeability activity identified a 50 kd substance presumably responsible for the increase in permeability to albumin. This factor was not related to the presence of nephrotic syndrome alone as no activity could be identified in patients with corticosteroid sensitive nephrotic syndrome and only low levels were found in patients with membranous nephropathy after transplantation or chronic renal failure. The ability to lower the level of serum activity in patients with recurrent FSGS by plasmapheresis and to demonstrate activity in the fluid removed support the hypothesis that a circulating serum factor causes the damage to the glomerular capillary in patients with recurrent FSGS resulting in proteinuria. The differences in permeability activity between patients with corticosteroid sensitive nephrotic syndrome and recurrent FSGS are against the hypothesis that these disorders in some way represent different manifestations of a disorder with similar immunologic etiology.

Comment: This article provides a major advance in the understanding of FSGS, demonstrating that at least in a significant subgroup of these patients, a circulating factor is associated with the proteinuria. It still remains to be shown how, if at all, this factor is responsible for the glomerular injury. This factor still needs further characterization but the ability to identify and remove it offers potential treatment options for patients with this form of FSGS. N. Kevin Krane, M.D., Tulane University

The abstract of this paper is available from the National Library of Medicine's PubMed site: click here .

EDITORIAL by Dr. Phillipe Lesavre