title: Incidence of and risk factors for severe acute kidney injury in children with heart failure treated with renin-angiotensin system inhibitors.
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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  • 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.
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Terano
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. kenzo@ii.e-mansion.com.|Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. kenzo@ii.e-mansion.com.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishikura
authors.affiliation: Department of Cardiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Riku
authors.initials: R
authors.lastname: Hamada
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Harada
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Pediatric Nephrology, Faculty of Medicine, Toho University, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hamasaki
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hataya
authors.affiliation: Japan Clinical Research Support Unit, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Honda
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D000293:Adolescent; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D011379:Prognosis; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Acute kidney injury; Angiotensin receptor blockers; Angiotensin-converting enzyme inhibitors; Cardiac surgery; Dehydration; Heart failure