Permeability Factor in Focal Segmental Glomerulosclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Reduction in Proteinuria in Recurrent FSGS Following Renal Transplant With Plasma Exchange and Cyclophosphamide.
研究概览
简要总结
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.
详细描述
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 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Plasma Exchange + Cyclophosphamide
Procedure/Surgery: Plasma exchange A course of plasma exchange of 5 treatments over 10 days, then administration of cyclophosphamide.
Drug: Cyclophosphamide For GFR > 50 ml/min/1.73 m2 received oral cyclophosphamide at a dose of 2 mg/kg/ day for 3 months. For GFR < 50 ml/min/1.73 m2 but > 10 ml/min/1.73 m2 will receive oral cyclophosphamide at a 25% reduced dose or 1.5 mg/kg/d for 3 months.
干预措施: Plasma exchange (Procedure)
Plasma Exchange + Cyclophosphamide
Procedure/Surgery: Plasma exchange A course of plasma exchange of 5 treatments over 10 days, then administration of cyclophosphamide.
Drug: Cyclophosphamide For GFR > 50 ml/min/1.73 m2 received oral cyclophosphamide at a dose of 2 mg/kg/ day for 3 months. For GFR < 50 ml/min/1.73 m2 but > 10 ml/min/1.73 m2 will receive oral cyclophosphamide at a 25% reduced dose or 1.5 mg/kg/d for 3 months.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Reduction in Proteinuria in Recurrent FSGS Following Renal Transplant With Plasma Exchange and Cyclophosphamide.
时间窗: every 3 months up to a year followed with native kidneys
Outcomes for FSGS occurring in native kidneys: A. Complete remission: proteinuria \<0.3 g/d ; B. Partial remission: proteinuria between 0.3 and 2 g/d ; C. Incomplete response: proteinuria between 2 and 3.5 g/d ; D. Relapse: return to proteinuria ≥3.5 g/d ; Note that counts within each category A-D may be summarized relative to remaining categories, as a proportion (relative to complement of the whole group count) with calculations implicitly based on zero/one valued binary variables, whose means are proportions, so to report 95% confidence intervals calculated using an exact binomial distribution.
次要结局
- Define the Kinetics of FPF in FSGS Patients Receiving Immunomodulatory Therapy or Plasma Exchange.(End of study)
- Comparison of RNA Expression Profiles in PBMC From Patients With FPF, Without FPF and Control Subjects(End of study)
- Determine Whether Renal Transplantation in Patients Whose Elevated FPF Levels Have Been Reduced for a Sustained Period is Associated With a Reduced Prevalence of Recurrent FSGS.(End of study)
- Correlate the Effect of Immunosuppressive Agents Which Reduce Proteinuria in Recurrent FSGS With the Effect on FPF Levels(End of study)