Randomized Controlled Trial of Mycophenolate Mofetil in Children, Adolescents, and Adults With IgA Nephropathy

Ronald J. Hogg, R. Curtis Bay, J. Charles Jennette, Richard Sibley, Sumit Kumar, Fernando Custodio Fervenza, Gerald Appel, Daniel Cattran, Danny Fischer, R. Morrison Hurley, Jorge Cerda, Brad Carter, Beverly Jung, German Hernandez, Debbie Gipson, Robert J. Wyatt

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Abstract

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), ≥0.6 g/g (males) or ≥0.8 g/g (females); and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2 (≥40 mL/min/1.73 m2 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 ≥ 0.6 g/g (males) and ≥0.8 g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36 mg/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 <0.2 g/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.

Original languageEnglish (US)
Pages (from-to)783-791
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume66
Issue number5
DOIs
StatePublished - Nov 1 2015

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Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Hogg, R. J., Bay, R. C., Jennette, J. C., Sibley, R., Kumar, S., Fervenza, F. C., Appel, G., Cattran, D., Fischer, D., Hurley, R. M., Cerda, J., Carter, B., Jung, B., Hernandez, G., Gipson, D., & Wyatt, R. J. (2015). Randomized Controlled Trial of Mycophenolate Mofetil in Children, Adolescents, and Adults With IgA Nephropathy. American Journal of Kidney Diseases, 66(5), 783-791. https://doi.org/10.1053/j.ajkd.2015.06.013