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Article Review/Hyperlink
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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
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