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Incidence of and risk factors for severe acute kidney injury in children with heart failure treated with renin–angiotensin system inhibitors

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Abstract

No large cohort study has yet determined the incidence of acute kidney injury (AKI) in children with heart failure treated with renin–angiotensin system (RAS) inhibitors. We thus retrospectively analyzed the incidence and risk factors for severe AKI (stages 2–3 according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines) at our institutions from 2008 to 2011. Among 312 children (162 boys; median age, 7.3 months), 59 cases of AKI occurred in 45 children. The incidence of AKI was 14.3 cases per 100 person-years overall (follow-up 413.6 person-years), or 27.3, 16.8, and 4.5 cases per 100 person-years in children aged <1, 1–3, and ≥4 years, respectively. Among them, 23 (39.0 %) children had metabolic acidosis and 14 (23.7 %) had hyperkalemia. Younger age, myocardial disease, cyanotic congenital heart disease, use of spironolactone, and cardiac surgery were independent risk factors for AKI. Furthermore, 37.3 % of children suffered dehydration during AKI.

Conclusion: AKI incidence is relatively high in children, particularly younger children, with heart failure treated using RAS inhibitors. Careful monitoring of renal function and serum electrolytes is essential. Proper management of fluid balance after infection and cardiac surgery may reduce the risk of AKI. Temporary discontinuation in RAS inhibitors should be considered during dehydration or surgery.

What is known:

• Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the two main classes of renin–angiotensin system (RAS) inhibitors used to treat hypertension, heart failure, and chronic kidney disease. Acute kidney injury (AKI) and hyperkalemia are potentially life-threatening complications associated with the use of ACEIs and ARBs. Some reports have suggested that dehydration and cardiac surgery are risk factors for AKI in children. However, no large-scale cohort studies have determined the incidence of AKI, its risk factors, and its outcomes in children with heart failure treated with ACEIs and/or ARBs.

What is new:

• In this retrospective cohort study, we determined the incidence, severity, and risk factors for severe AKI in children with heart failure treated with ACEIs and/or ARBs. The incidence of AKI in these children was relatively high (14.3 episodes per 100 person-years). In addition, younger age, myocardial disease, cyanotic congenital heart disease, concomitant use of spironolactone, and cardiac surgery were risk factors for AKI. Furthermore, 37.3 % of children had dehydration during AKI episodes.

• Our results suggested that appropriate fluid balance after infection and cardiac surgery might reduce the risk of AKI and its complications. Temporary discontinuation or reductions in the levels of ACEIs and/or ARBs during dehydration or before surgery may also be warranted in these patients.

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Abbreviations

ACEI:

angiotensin-converting enzyme inhibitor

AKI:

acute kidney injury

ARB:

angiotensin receptor blocker

CHF:

chronic heart failure

CKD:

chronic kidney disease

eGFR:

estimated glomerular filtration rate

KDIGO:

Kidney Disease Improving Global Outcomes

RAS:

renin–angiotensin system

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Acknowledgments

The authors wish to thank Nicholas Smith, PhD, an employee of Edanz Group Ltd, for providing the language editorial support in the preparation of this manuscript.

Authors’ contributions

We confirm that all authors have made substantial contributions to the conception and design, or acquisition of data, or analysis and interpretation of data, or to the drafting of the article or its critical revision for important intellectual content. Further, we confirm that all authors have given final approval of the version to be published and its submission to the European Journal of Pediatrics.

In particular, each author made the following contributions:

Chikako Terano: Dr. Terano was the principal investigator and prepared the manuscript.

Kenji Ishikura: Dr. Ishikura oversaw the research.

Masaru Miura: Dr. Miura established the treatment protocol for pediatric heart failure for our institution that was used in this study and also established the database of all children treated for heart failure.

Riku Hamada, Ryoko Harada: Drs. Hamada and Harada performed the data management.

Tomoyuki Sakai and Yuko Hamasaki: Drs. Sakai and Hamasaki collected the data.

Takashi Ando: Mr. Ando performed the statistical analyses.

Masataka Honda and Hiroshi Hataya: Drs. Honda and Hataya planned the survey and designed the protocol.

Author information

Authors and Affiliations

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

    Chikako Terano, Kenji Ishikura, Riku Hamada, Ryoko Harada, Hiroshi Hataya & Masataka Honda

  2. Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Kenji Ishikura

  3. Department of Cardiology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Masaru Miura

  4. Department of Pediatrics, Shiga University of Medical Science Hospital, Shiga, Japan

    Tomoyuki Sakai

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

    Yuko Hamasaki

  6. Japan Clinical Research Support Unit, Tokyo, Japan

    Takashi Ando

Authors
  1. Chikako Terano
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  2. Kenji Ishikura
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  3. Masaru Miura
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  8. Hiroshi Hataya
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  9. Takashi Ando
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  10. Masataka Honda
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Corresponding author

Correspondence to Kenji Ishikura.

Ethics declarations

The present study was designed and conducted in accordance with the ethical standards of the Declaration of Helsinki and the ethical guidelines for epidemiological studies issued by the Ministry of Health, Labour and Welfare in Japan. This study was approved by the ethics committee of Tokyo Metropolitan Children’s Medical Center (ID: H23-112) before starting data collection. Because data were retrospectively retrieved from the patients’ medical records, informed consent was not obtained in accordance with these ethical guidelines.

Conflict of interest

Kenji Ishikura has received lecture fees from Novartis Pharma. Yuko Hamasaki has received research grants from Novartis Pharma and lecture fees from Novartis Pharma and Astellas Pharma. Masataka Honda has received lecture fees from Novartis Pharma and Takeda Pharmaceutical Company. The other authors have no conflicts of interest to declare.

Additional information

Communicated by Mario Bianchetti

Revisions received: 14 August 2015; 16 November 2015

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Terano, C., Ishikura, K., Miura, M. et al. Incidence of and risk factors for severe acute kidney injury in children with heart failure treated with renin–angiotensin system inhibitors. Eur J Pediatr 175, 631–637 (2016). https://doi.org/10.1007/s00431-015-2680-8

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  • DOI: https://doi.org/10.1007/s00431-015-2680-8

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