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Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study)

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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 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.

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Acknowledgments

The authors wish to thank all of the participants and attending physicians for their contributions.

Funding

This study was supported by Health and Labor Sciences Research Grants (Research on Children and Families) from the Japanese Ministry of Health Labor and Welfare, and in part by a research grant from the Kidney Foundation, Japan.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Wakayama Medical University, Wakayama, Japan

    Yuko Shima

  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

    Koichi Nakanishi

  3. Division of Clinical Trials, Department of Clinical Research Promotion, Clinical Research Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan

    Mayumi Sako

  4. Department of Medical Statistics Faculty of Medicine, Toho University, Ota-Ku, Tokyo, Japan

    Mari Saito-Oba

  5. Department of Pediatric Nephrology, Faculty of Medicine, Toho University, Ota-Ku, Tokyo, Japan

    Yuko Hamasaki

  6. Department of General Pediatrics, Tokyo Metropolitan Children’s Medical Center, Fuchu, Tokyo, Japan

    Hiroshi Hataya

  7. Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Fuchu, Tokyo, Japan

    Masataka Honda

  8. Department of Nephrology and Rheumatology, National Center for Child Health and Development, Setagaya-Ku, Tokyo, Japan

    Koichi Kamei & Kenji Ishikura

  9. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa, Japan

    Shuichi Ito

  10. Department of Nephrology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Hiroshi Kaito & Ryojiro Tanaka

  11. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

    Kandai Nozu & Kazumoto Iijima

  12. Clinical Research Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan

    Hidefumi Nakamura

  13. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Bunkyo-Ku, Tokyo, Japan

    Yasuo Ohashi

  14. Clinical Research Center, Wakayama Medical University, Wakayama, Japan

    Norishige Yoshikawa

Authors
  1. Yuko Shima
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  2. Koichi Nakanishi
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  3. Mayumi Sako
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  15. Yasuo Ohashi
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  16. Kazumoto Iijima
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Consortia

for the Japanese Study Group of Kidney Disease in Children (JSKDC)

Corresponding author

Correspondence to Koichi Nakanishi.

Ethics declarations

The study was approved by the institutional review board at each center and complied with the Declaration of Helsinki. Written assent was obtained from patients who were old enough to understand and written informed consent was obtained from all of their parents.

Disclosures

KN received lecture fees from AstraZeneca and Daiichi Sankyo, Co. Ltd. MH received lecture fees from Pfizer Japan Inc. and KYORIN Pharmaceutical Co., Ltd. KI received lecture fees from Daiichi Sankyo, Co., Ltd. and grant from Pfizer Japan Inc. SI received lecture fees from Mylan Inc., AstraZeneca, Pfizer Japan Inc., Shionogi & Co. Ltd., Daiichi Sankyo, Co. Ltd., Meiji Seika Pharma Co., and grant from Pfizer Japan Inc., Merck & Co. YO received consulting fees from Shionogi & Co. Ltd. KI received a grant from Daiichi Sankyo, Co., Ltd., lecture fees and/or consulting fees from Daiichi Sankyo, Co., Ltd., Takeda Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., NY. The other authors had no disclosure to declare.

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Shima, Y., Nakanishi, K., Sako, M. et al. Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study). Pediatr Nephrol 34, 837–846 (2019). https://doi.org/10.1007/s00467-018-4099-8

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  • DOI: https://doi.org/10.1007/s00467-018-4099-8

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