Savin and colleagues have spent the past 20 years
purifying and attempting to identify the circulating factor that causes
recurrence of FSGS and contributes to the genesis of FSGS in about 30%
of patients. They have studied the plasma or serum of more than 500
patients and have used material from several of these patients,
including Van Todd Whitlock, founder of the FSGR Foundation, to
partially purify and characterize the molecule that is responsible for
kidney injury in FSGS. This substance is sometimes called the
permeability factor or the Savin-Whitlock factor. These studies are
possible because they developed a laboratory test that shows the effect
of a small amount of serum or plasma on the permeability of glomeruli
that have been isolated from normal rat kidneys. They have shown that
serum from certain FSGS patients severely damages glomeruli and
increases their albumin permeability or Palb. They propose
that this effect may be a cause of proteinuria in FSGS.
These investigators found that the degree of damage
after brief exposure to patient serum is correlated with the rate of
progression to kidney failure and with the likelyhood of recurrence
after transplantation. They also showed that plasmapheresis, a treatment
in which plasma is discarded and replaced with a solution of normal
albumin or with normal plasma, decreases activity and often decreases
proteinuria in recurrent FSGS. They propose that the results of this
test may be useful in assessing potential therapies for FSGS.
Recently, they found that the active factor adheres
to galactose coated beads used for purification and that galactose
solution neutralizes the activity in damaging glomeruli in laboratory
studies. They studied a single patient with recurrent FSGS in a kidney
transplant and found that a single intravenous dose of galactose
abolished the permeability activity of his serum completely. The same
patient later took galactose orally and had a similar decrease in
activity. This decrease reached its maximum only after about 4 weeks of
therapy.
They and other interested physicians initiated a
study to determine whether galactose given as a solution by mouth could
decrease the serum activity in children and adults with FSGS. They set
up a pilot study of patients with FSGS and proteinuria. Kidney function,
as indicated by creatinine and need for dialysis or transplant, ranged
from normal to very severe kidney failure. Some patients were on
dialysis and others had received transplants and were being treated for
recurrence. Patients from many states volunteered and entered the study.
Preliminary results are encouraging but have not been completely
reported.
A number of additional studies will be
required before the effects of galactose on the course of FSGS can be
assessed. These will include studies with a range of doses and a longer
treatment period as well as studies of the blood concentration of
galactose during treatment and of potential side effects of this
treatment. It is likely that galactose will be used in conjunction with
other standard therapies. The FSGS patient community has responded
enthusiastically to the study of this simple therapy. All of us hope
that galactose will provide a significant new way of treating FSGS
patients that will decrease their urine protein and help prevent
progression of their kidney disease.
