Mycophenolate Mofetil in Patients With Progressive Idiopathic Membranous Nephropathy (MMFPRIMER)

• Percentage of complete remission [ Time Frame: at 48 week after treatment ] [ Designated as safety issue: No ]
  Complete remission: Reduction in proteinuria to 200 mg per day with stable serum albumin with more than 3.5 g/dL
• Percentage of partial remission [ Time Frame: at 48 week after treatment ] [ Designated as safety issue: No ]
  Partial remission: Reduction in proteinuria to greater than 50 percent of initial values or absolute values of proteinuria between 200 mg and 3.5 g per day

• estimated Glomerular filtration rate (eGFR) [ Time Frame: at 48 week after treatment ] [ Designated as safety issue: No ]
  The change of eGFR mesured by Modification of Diet in Renal Disease (MDRD) study equation from baseline to 1 year after treatment
• Relapse [ Time Frame: For 48 weeks after treatment ] [ Designated as safety issue: No ]
  A relapse is return of proteinuria to approximately 3.5g/day in patients who had previously undergone a complete or partial remission
• Proteinuria [ Time Frame: at 48 week after treatment ] [ Designated as safety issue: No ]
  The change of proteinuria from baseline to 48 week after treatment
• Side effects [ Time Frame: For 48 weeks after treatment ] [ Designated as safety issue: Yes ]
  Any undesired effects of interventional drugs

Cyclosporin decreases proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a risk of side effects such as nephrotoxicity. The investigators plan to the study to evaluate whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effect.

Idiopathic membranous nephropathy is most common cause of glomerulonephritis in adults. Persistent high grade proteinuria or progressively decrease of renal function is a risk factor for end stage renal disease in idiopathic membranous nephropathy. It has been reported that cyclosporin in patients with idiopathic membranous nephropathy decreases proteinuria and improve renal function. Mycophenolate mofetil is a recently developed immunosuppressive agent with fewer side effect than cyclosporin. In this study patients with high risk group of progressive idiopathic membranous nephropathy will be treated with mycophenolate mofetil and low dose prednisone. The outcome will be compared to controls treated with cyclosporin and low dose prednisone.

• Drug: Mycophenolate mofetil, low dose steroid

  Mycophenolate Mofetil: Myconol capsule 250mg, Myconol 500 mg bid per day (less than 50kg), 750 ~ 1000 mg bid per day (more than 50kg)

  Steroid: Methylprednisone 4mg tablet or Prednisolone 5mg tablet or Deflazacort 6mg tablet. Prednisolone dose: 0.15mg/kg up to a maximum dose of 15mg/day

  Duration: 48 weeks

  Other Name: Myconol, MMF
• Drug: Cyclosporin, low dose steroid

  Cyclosporin: Implanta soft cap (cyclosporin microemulsion) 25mg/100mg, starting dose of 4mg/kg per day and titrate according to investigator's decision based on cyclosporin trough level (100±50 ng/ml)

  Steroid: same dosage with active comparator goup

  Duration: 48 weeks

  Other Name: Implanta soft capsule

• Experimental: Mycophenolate mofetil, low dose steroid
  Intervention: Drug: Mycophenolate mofetil, low dose steroid
• Active Comparator: Cyclosporin, low dose steroid
  Intervention: Drug: Cyclosporin, low dose steroid

Inclusion Criteria:

1. Patients with idiopathic membranous nephropathy
2. The duration of disease is less than twelve months
3. Patients with persistent proteinuria more than 8 grams per day
4. Patients who provided informed consent

5. The cases that satisfy more than three of following items even if proteinuria is less than 8 grams per day:

   • Serum creatinine (mg/dl) above normal
   • Hypertension
   • Nephrotic syndrome
   • Serum albumin (g/dL) < 1.5
   • Selectivity index > 0.2

Exclusion Criteria:

1. Severe digestive organ disease
2. Allergy history to clinical trial medication and acute or chronic allergy for 4 weeks recently.
3. Clinical history of treatment with other immunosuppressive medication
4. Probability of pregnancy, breast feeding woman
5. Uncontrolled hypertension (more than 160/100mmHg)
6. Uncontrolled systemic disease
7. Drug addiction or alcoholics within 6 months
8. eGFR is less than 30ml/min at screening
9. Abnormal liver function test (more than 3 times above compared with normal value)
10. Absolute neutrophil count <1,500/mm3 or leukocyte <2,500/mm3 or platelets <100,000/mm3
11. Secondary membranous nephropathy
12. Expected life expectancy is less than 1 year