Mycophenolate Mofetil for IgA Nephropathy
Condition: IGA Nephropathy
MeSH terms: Kidney Diseases; Glomerulonephritis, IGA
Study type: Interventional
Phase: Phase 4

Summary: 
      IgA nephropathy (IgAN) is the commonest primary glomerulonephritis worldwide. In Hong Kong,
      IgAN accounts for approximately 30% of all primary glomerular diseases, and a significant
      proportion of young patients (< 50 years of age) on dialysis therapy are sufferers of primary
      IgAN. To date, no specific therapeutic agent has been consistently shown to halt the
      progression of IgAN to end-stage renal failure, particularly in patients with persistent
      significant proteinuria and the presence of chronic tubulointerstitial inflammation on kidney
      biopsy. In recent years, angiotensin-converting enzyme inhibitors (ACEI) have been found
      capable of significantly reducing proteinuria in some IgAN patients, while others,
      particularly those with the ACE DD genotype, showed either absent or unsatisfactory response
      to angiotensin blockade. Mycophenolate mofetil (MMF) is a marketed immunosuppressive drug
      which acts by releasing mycophenolic acid (MPA) to inhibit the de novo pathway of purine
      synthesis, and hence is relatively selective for lymphocytes. Apart from being efficacious
      for the prophylaxis of renal allograft rejection and for the induction of remission in severe
      lupus nephritis, MMF has been anecdotally reported to avert progression to allograft failure
      in recurrent IgAN of the transplanted kidney. Data on the clinical efficacy of MMF in the
      treatment of primary IgAN, however, is lacking. In the current proposal, we aim to study the
      clinical efficacy of MMF in patients with biopsy-proven IgAN and clinically significant
      proteinuria despite angiotensin blockade. Patients will be followed up for at least 5 years
      to track any survival difference between groups.
    

Detailed description: 
      (i) STUDY DESIGN

      This will be a prospective, randomized, open-label, case-controlled study. Patients of either
      gender with biopsy-proven IgAN and clinically significant proteinuria despite being on ACEI
      treatment will be potential candidates (see selection criteria). Eligible patients will be
      randomized into either of the following groups:

      Group I (Intervention arm):

      Patients will be given MMF at a daily dose of 1.5 g orally in 2 divided doses in addition to
      concurrent medications, including ACEI. Duration of therapy is expected to be six months.

      Group II (Control arm):

      Patient will continue to receive all concurrent medications, including ACEI or angiotensin
      receptor blocker, at the discretion of the attending renal physician.

      (ii) PATIENT SELECTION CRITERIA Inclusion criteria

        -  Males or females between the ages of 18 and 70 years

        -  Renal biopsy showing a histological diagnosis IgAN, with predominant or codominant
           mesangial deposition of IgA on immunofluorescent studies

        -  Daily urinary protein excretion > 1 g on at least 3 separate occasions

        -  Serum creatinine < 400 umol/L

        -  Patients who are willing to give written informed consent and to participate in and
           comply with the study protocol

      Exclusion criteria

        -  Presence of concomitant glomerular diseases

        -  Patients with known hypersensitivity to MMF

        -  Patients receiving treatment with other cytotoxic agents

        -  Serum creatinine > 400 umol/L

        -  Women who are lactating, pregnant or of childbearing potential not using, or who are
           unwilling to use, a reliable contraceptive method during and for 6 weeks following
           conclusion of MMF therapy. A pregnancy test to exclude pregnancy will be performed for
           women of childbearing potential prior to recruitment

        -  Patients who are unable or unwilling to give written informed consent and to participate
           in and comply with the study protocol

        -  Presence of systemic infection or malignancy requiring therapy at the time of entry to
           the study

        -  Patients simultaneously participating in another study or who have participated in
           another study within the last 30 days of entry into this study

      (iii) PATIENT MONITORING

      Patient record

      The record of every recruited patient will contain the following information:

        -  Demographic data

        -  Medical history including concomitant illness

        -  All concomitant medications

        -  Other significant information

      Timing of Assessments

      All study assessments will be calculated from the date of study entry. The study follow-up
      schedule will be as follows:

        -  Baseline, then

        -  Two-weekly for the first month, then

        -  Monthly for the 2nd - 6th month, at the end of which MMF will be withdrawn, then

        -  Three-monthly until at least 5 years of follow up
    

Intervention name(s): mycophenolate mofetil; angiotensin blockade
Intervention type(s): Drug; Drug
Intervention description(s): Orally at 0.75 g bd to 1 g bd for 6 months; Continuation of angiotensin blockade
Intervention MeSH terms: Mycophenolic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: proteinuria; creatinine; kidney survival; ESRD