Yuko Shima1, Koichi Nakanishi2, Mayumi Sako3, Mari Saito-Oba4, Yuko Hamasaki5, Hiroshi Hataya6, Masataka Honda7, Koichi Kamei8, Kenji Ishikura8, Shuichi Ito9, Hiroshi Kaito10, Ryojiro Tanaka10, Kandai Nozu11, Hidefumi Nakamura12, Yasuo Ohashi13, Kazumoto Iijima11, Norishige Yoshikawa14. 1. Department of Pediatrics, Wakayama Medical University, Wakayama, Japan. 2. Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, 207 Uehara Nishihara-Cho, Nakagami-Gun, Okinawa, 903-0125, Japan. knakanis@med.u-ryukyu.ac.jp. 3. Division of Clinical Trials, Department of Clinical Research Promotion, Clinical Research Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan. 4. Department of Medical Statistics Faculty of Medicine, Toho University, Ota-Ku, Tokyo, Japan. 5. Department of Pediatric Nephrology, Faculty of Medicine, Toho University, Ota-Ku, Tokyo, Japan. 6. Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan. 7. Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan. 8. Department of Nephrology and Rheumatology, National Center for Child Health and Development, Setagaya-Ku, Tokyo, Japan. 9. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa, Japan. 10. Department of Nephrology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan. 11. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. 12. Clinical Research Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan. 13. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Bunkyo-Ku, Tokyo, Japan. 14. Clinical Research Center, Wakayama Medical University, Wakayama, Japan.
Abstract
BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. METHODS: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoinglisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. CONCLUSIONS: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .
RCT Entities:
BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. METHODS: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. CONCLUSIONS: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .
Entities:
Keywords:
Children; IgA nephropathy; Lisinopril; Losartan; Randomized controlled trial
Authors: G Maschio; D Alberti; G Janin; F Locatelli; J F Mann; M Motolese; C Ponticelli; E Ritz; P Zucchelli Journal: N Engl J Med Date: 1996-04-11 Impact factor: 91.245