Ronald J Hogg1, R Curtis Bay2, J Charles Jennette3, Richard Sibley4, Sumit Kumar5, Fernando C Fervenza6, Gerald Appel7, Daniel Cattran8, Danny Fischer9, R Morrison Hurley10, Jorge Cerda11, Brad Carter12, Beverly Jung13, German Hernandez14, Debbie Gipson15, Robert J Wyatt16. 1. Baylor Scott and White Healthcare, Temple, TX. Electronic address: ronjhogg@gmail.com. 2. A.T. Still University, Mesa, AZ. 3. University of North Carolina at Chapel Hill, NC. 4. Stanford University, Stanford, CA. 5. Dallas Nephrology Associates, Dallas, TX. 6. Mayo Clinic, Rochester, MN. 7. Columbia University, New York, NY. 8. Toronto General Hospital, Toronto, Ontario, Canada. 9. Kidney and Hypertension, Cincinnati, OH. 10. BC Children's Hospital, Vancouver, British Columbia, Canada. 11. Capital Dist Renal Physicians, Albany, NY. 12. Kidney Specialists of Central Oklahoma, Oklahoma City, OK. 13. St. Paul's Hospital, Vancouver, British Columbia, Canada. 14. Texas Tech University Health Science Center, El Paso, TX. 15. University of Michigan, Ann Arbor, MI. 16. University of Tennessee Health Science Center, Memphis, TN.
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), ≥0.6g/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 withMMF (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 afterlisinopril/losartan plus Omacor.
RCT Entities:
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 MMFpatients 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.
Authors: Richard A Lafayette; Pietro A Canetta; Brad H Rovin; Gerald B Appel; Jan Novak; Karl A Nath; Sanjeev Sethi; James A Tumlin; Kshama Mehta; Marie Hogan; Stephen Erickson; Bruce A Julian; Nelson Leung; Felicity T Enders; Rhubell Brown; Barbora Knoppova; Stacy Hall; Fernando C Fervenza Journal: J Am Soc Nephrol Date: 2016-11-07 Impact factor: 10.121
Authors: Thomas Rauen; Christina Fitzner; Frank Eitner; Claudia Sommerer; Martin Zeier; Britta Otte; Ulf Panzer; Harm Peters; Urs Benck; Peter R Mertens; Uwe Kuhlmann; Oliver Witzke; Oliver Gross; Volker Vielhauer; Johannes F E Mann; Ralf-Dieter Hilgers; Jürgen Floege Journal: J Am Soc Nephrol Date: 2017-10-17 Impact factor: 10.121