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:~To identify a population of FSGS patients with elevated FPF levels~To examine RNA expression profiles of peripheral blood mononuclear cells (PBMC)~in FSGS patients with elevated FPF levels~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~To identify immunosuppressive agents which are successful in inducing sustained~reduction in FPF levels~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.
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:~To identify a population of FSGS patients with elevated FPF levels~To examine RNA expression profiles of peripheral blood mononuclear cells (PBMC) in FSGS patients with elevated FPF levels~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~To identify immunosuppressive agents which are successful in inducing sustained reduction in FPF levels~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.