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.
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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