Acute kidney injury in Ugandan children with severe malaria is associated with long-term behavioral problems

Meredith R. Hickson, Andrea L. Conroy, Paul Bangirana, Robert O. Opoka, Richard Idro, John M. Ssenkusu, Chandy C. John

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17 Scopus citations


Background Acute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown. Methods We conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity. Results AKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age. Conclusions AKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.

Original languageEnglish (US)
Article numbere0226405
JournalPloS one
Issue number12
StatePublished - Dec 2019

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ, and the Fogarty International Center (D43 NS078280 to CCJ, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the children and their parents who participated in this study, the study team for their dedicated effort in treating the children and collecting the data.

Publisher Copyright:
Copyright: © 2019 Hickson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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