Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria

Andrea L. Conroy, Robert O. Opoka, Paul Bangirana, Richard Idro, John M. Ssenkusu, Dibyadyuti Datta, James S Hodges, Catherine Morgan, Chandy C. John

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


BACKGROUND: Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown.

METHODS: Ugandan children with cerebral malaria (CM, n = 260) and severe malaria anemia (SMA, n = 219) or community children (CC, n = 173) between 1.5 and 12 years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children < 5 and Kaufman Assessment Battery for Children (K-ABC) second edition in children ≥ 5 years of age.

RESULTS: The prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p = 0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p = 0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p = 0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p < 0.0001). In CM, AKI was associated with the presence and severity of retinopathy (p < 0.05) and increased cerebrospinal fluid albumin suggestive of blood-brain barrier disruption.

CONCLUSIONS: AKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.

Original languageEnglish (US)
Article number98
JournalBMC medicine
Issue number1
StatePublished - May 21 2019

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurological Disorders and Stroke and the Fogarty International Center (grants R01NS055349 and D43 NS078280).

Publisher Copyright:
© 2019 The Author(s).


  • Acute kidney injury
  • Child
  • Chronic kidney disease
  • Cognition
  • Malaria
  • Mortality
  • Severity of Illness Index
  • Cognition Disorders/epidemiology
  • Prevalence
  • Prospective Studies
  • Acute Kidney Injury/complications
  • Hospital Mortality
  • Humans
  • Malaria/complications
  • Risk Factors
  • Child, Preschool
  • Uganda/epidemiology
  • Infant
  • Male
  • Renal Insufficiency, Chronic/complications
  • Malaria, Cerebral/complications
  • Female
  • Retrospective Studies
  • Cohort Studies

PubMed: MeSH publication types

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


Dive into the research topics of 'Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria'. Together they form a unique fingerprint.

Cite this