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Efficacy and safety of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for IgA nephropathy in children

  • Systematic Review/Meta-analysis
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Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

IgA nephropathy (IgAN) is one of the most prevalent primary glomerulopathies in children. There are various studies investigating the efficacy of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in adults with IgAN. However, only few studies evaluated the efficacy of these medications in pediatric patients.

Objective

To evaluate the efficacy and safety of ACEI/ARB in children with IgAN.

Data sources

Databases including PubMed, Web of Science, Cochrane, Scopus, and Google Scholar were searched between the 1st of April and 20th of July of 2021 using the keywords “IgA Nephropathy,” “Berger's Disease,” “Angiotensin-Converting Enzyme Inhibitors,” “Angiotensin Receptor Antagonists,” “Angiotensin II Type 1 Receptor Blockers,” and similar entry terms collected from the Medical Subject Headings (MeSH).

Study eligibility criteria

Observational studies (case series, case–control, cohort, and cross-sectional) and clinical trials with descriptions of pediatric patients (under 19 years old) with histopathological diagnosis of IgA nephropathy and who received ACEI and/or ARB.

Participants and interventions

Pediatric patients (under 19 years old) with histopathological diagnosis of IgA nephropathy and who received ACEI and/or ARB.

Study appraisal

For quality assessment, the Risk of Bias 2 tool (RoB 2), the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I), the National Institutes of Health (NIH) quality assessment tool, and the Newcastle–Ottawa Scale (NOS) were used.

Results

After recovering 1,471 studies, only eight, published between 2003 and 2019, met the eligibility criteria and were included in this systematic review. Of the 737 included children in the studies, 202 (25.8%) used ACEI/ARB and were compared with placebo and other therapy regimens. Of the seven studies that evaluated proteinuria, six reported an efficacy of ACEI/ARB in reducing this marker. ACEI/ARB also showed a possible effect in reducing hematuria and oxidative stress. The most common side effect was dizziness.

Limitations

The number of studies about the treatment with ACEI/ARB in children with IgAN is scarce. In addition, the studies are very heterogeneous. There are few studies that compared ACEI/ARB with placebo.

Conclusions and implications of key findings

The use of ACEI and/or ARB appears to be safe and to reduce proteinuria in pediatric patients with IgAN. Nonetheless, further randomized controlled trials, with greater methodological rigor and longer follow-up time, are required to establish the efficacy and safety of this therapy in this population.

Systematic review registration number

The protocol of this systematic literature review was registered in PROSPERO under the number CRD42021245375, and in the OSF registries (https://osf.io/qft4z/) with the registration https://doi.org/10.17605/OSF.IO/VADYR.

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Funding

This work was partially supported by Brazilian National Council of Research Development (CNPq—Grant # 302153/2019-5), Coordination of High Education Level Personnel (CAPES), and Foundation of Research of Minas Gerais (FAPEMIG).

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Authors and Affiliations

  1. Interdisciplinary Laboratory of Medical Investigation, Unit of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Alfredo Balena Avenue, 190, 2nd Floor, Room # 281, Belo Horizonte, MG, 30130-100, Brazil

    Pedro Alves Soares Vaz de Castro, Letícia Bitencourt, Bruno Wilnes Simas Pereira, Ananda Queiroz Rocha Lima, Henrique Santos Hermida, Carlos Roberto Moreira Neto, Mariana Dinamarco Mestriner & Ana Cristina Simões e Silva

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  1. Pedro Alves Soares Vaz de Castro
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Contributions

PASVC, LB, BWSP, AQRL, HSH, CRMN, and MDM registered the study in PROPERO and in Open Science Framework. PASVC, LB, BWSP, AQRL, HSH, CRMN, and MDM made the literature revision and selection of the articles to be included. BWSP, AQRL, HSH, CRMN, and MDM extracted data from the selected articles. PASVC and LB checked data extraction and evaluated the quality of selected articles. PASVC, LB, BWSP, AQRL, HSH, CRMN, and MDM wrote the first draft. ACSS conceptualized the study, made general supervision, and revised the manuscript. ACSS submitted the final version of the manuscript, which is approved by all authors.

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Correspondence to Ana Cristina Simões e Silva.

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Vaz de Castro, P.A.S., Bitencourt, L., Pereira, B.W.S. et al. Efficacy and safety of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for IgA nephropathy in children. Pediatr Nephrol 37, 499–508 (2022). https://doi.org/10.1007/s00467-021-05316-0

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