Permeability Factor in Focal Segmental Glomerulosclerosis
Status:
Completed
Trial end date:
2014-06-01
Target enrollment:
Participant gender:
Summary
Focal segmental glomerulosclerosis (FSGS) is a renal syndrome characterized by proteinuria
(usually nephrotic range), limited response to conventional therapy, and a poor renal
prognosis, with progression to end stage renal failure in at least 50% of patients. As a
syndrome, FSGS likely has many specific etiologies, only a few of which are well-defined.
Recently, it has been suggested that some idiopathic FSGS patients have elevated circulating
levels of a protein that induces glomerular permeability in vitro and in vivo. While there
has been no consistent term for this factor, it will be termed here FSGS permeability factor
(FPF).
The purposes of the present study are five fold:
1. To identify a population of FSGS patients with elevated FPF levels
2. To examine RNA expression profiles of peripheral blood mononuclear cells (PBMC) in FSGS
patients with elevated FPF levels
3. To define the kinetics of FPF disappearance and reappearance in FSGS patients receiving
immunomodulatory therapy and in the case of patients with recurrent FSGS following renal
transplant, those receiving plasma exchange
4. To identify immunosuppressive agents which are successful in inducing sustained
reduction in FPF levels
5. To determine in patients with FSGS who are awaiting renal transplant, whether sustained
reduction in FPF levels is associated with reduced risk of recurrent FSGS.
Patient participation is divided into an evaluation phase, in which FPF levels, RNA
expression profiles, and patient eligibility for participation in treatment protocols are
determined, and a treatment phase in which specific immunomodulatory therapy is introduced in
an open label fashion. We propose to define carefully the relationship between elevated FPF
and remission of proteinuria in patients with FSGS in native kidneys, following treatment
with standard therapies (daily prednisone, cyclophosphamide) and experimental therapies
(pulse dexamethasone, pirfenidone). In patients with recurrent FSGS in renal allografts, we
will determine the kinetics of FPF following plasma exchange and following plasma exchange
plus cyclophosphamide. In patients with elevated FPF levels who are awaiting renal
transplantation, we will determine the kinetics of FPF following plasma exchange and
following plasma exchange plus cyclophosphamide, and examine the rate of recurrent FSGS in
these patients.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)