Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy

Am J Kidney Dis. 2015 Nov;66(5):783-91. doi: 10.1053/j.ajkd.2015.06.013. Epub 2015 Jul 21.


Background: Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results.

Study design: Double-blind placebo-controlled randomized controlled trial.

Setting & participants: 52 children, adolescents, and adults with biopsy-proven IgAN in 30 centers in the United States and Canada. Entry criteria: age older than 7 to younger than 70 years; urine protein-creatinine ratio (UPCR), ≥0.6g/g (males) or ≥0.8g/g (females); and estimated glomerular filtration rate ≥ 50mL/min/1.73m(2) (≥40mL/min/1.73m(2) if receiving angiotensin-converting enzyme inhibitor). Mean age, 32±12 (SD) years; 62% men; and 73% white.

Intervention: Lisinopril (or losartan) plus a highly purified omega-3 fatty acid (Omacor [Pronova Biocare]) was given to 94 patients for 3 months; 52 of the patients with persistent UPCR≥0.6g/g (males) and ≥0.8g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36mg/kg/d) in addition to lisinopril/losartan plus Omacor.

Outcomes: Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment.

Measurements: UPCR measured on 24-hour urine samples. Glomerular filtration rate estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age ≥ 18 years) formula.

Results: 44 patients completed 6 months of treatment with MMF (n=22) or placebo (n=22). The trial was terminated early at the recommendation of the Data Monitoring Committee because of the lack of benefit. No patient achieved a complete remission (UPCR<0.2g/g). Mean UPCRs at randomization and after 6 months were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95% CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean difference in UPCR change between these groups (MMF minus placebo) was -0.22 (95% CI, -0.75 to 0.31; P=0.4). Adverse events were rare apart from nausea (MMF, 8.7%; placebo, 3.7%); one of these MMF patients withdrew.

Limitations: Low patient enrollment and short follow-up.

Conclusions: MMF did not reduce proteinuria significantly in patients with IgAN who had persistent proteinuria after lisinopril/losartan plus Omacor.

Keywords: IgA nephropathy (IgAN); MEST scores; Mycophenolate mofetil (MMF); proteinuria; randomized controlled trial (RCT); remission; urinary protein-creatinine ratio (UPCR).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Child
  • Creatinine / urine
  • Dietary Supplements
  • Docosahexaenoic Acids / therapeutic use
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Eicosapentaenoic Acid / therapeutic use
  • Female
  • Glomerular Filtration Rate*
  • Glomerulonephritis, IGA / drug therapy*
  • Glomerulonephritis, IGA / pathology
  • Glomerulonephritis, IGA / urine
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lisinopril / therapeutic use
  • Losartan / therapeutic use
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Proteinuria
  • Remission Induction
  • Treatment Outcome
  • Young Adult


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Drug Combinations
  • Immunosuppressive Agents
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Creatinine
  • Omacor
  • Lisinopril
  • Mycophenolic Acid
  • Losartan