title: Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy.
abstract: BACKGROUND
  Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results.
  
  
  METHODS
  Double-blind placebo-controlled randomized controlled trial.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Baylor Scott and White Healthcare, Temple, TX. Electronic address: ronjhogg@gmail.com.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hogg
authors.affiliation: A.T. Still University, Mesa, AZ.
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Bay
authors.affiliation: University of North Carolina at Chapel Hill, NC.
authors.forename: J Charles
authors.initials: JC
authors.lastname: Jennette
authors.affiliation: Stanford University, Stanford, CA.
authors.forename: Richard
authors.initials: R
authors.lastname: Sibley
authors.affiliation: Dallas Nephrology Associates, Dallas, TX.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.affiliation: Columbia University, New York, NY.
authors.forename: Gerald
authors.initials: G
authors.lastname: Appel
authors.affiliation: Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cattran
authors.affiliation: Kidney and Hypertension, Cincinnati, OH.
authors.forename: Danny
authors.initials: D
authors.lastname: Fischer
authors.affiliation: BC Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: R Morrison
authors.initials: RM
authors.lastname: Hurley
authors.affiliation: Capital Dist Renal Physicians, Albany, NY.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cerda
authors.affiliation: Kidney Specialists of Central Oklahoma, Oklahoma City, OK.
authors.forename: Brad
authors.initials: B
authors.lastname: Carter
authors.affiliation: St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Beverly
authors.initials: B
authors.lastname: Jung
authors.affiliation: Texas Tech University Health Science Center, El Paso, TX.
authors.forename: German
authors.initials: G
authors.lastname: Hernandez
authors.affiliation: University of Michigan, Ann Arbor, MI.
authors.forename: Debbie
authors.initials: D
authors.lastname: Gipson
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wyatt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002648:Child; D003404:Creatinine / Q000652:urine; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017706:Lisinopril / Q000627:therapeutic use; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011507:Proteinuria; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D003404:Creatinine; C405603:Omacor; D017706:Lisinopril; D009173:Mycophenolic Acid; D019808:Losartan
keywords: IgA nephropathy (IgAN); MEST scores; Mycophenolate mofetil (MMF); proteinuria; randomized controlled trial (RCT); remission; urinary protein-creatinine ratio (UPCR)