Alterations in Systemic Extracellular Heme and Hemopexin Are Associated with Adverse Clinical Outcomes in Ugandan Children with Severe Malaria

Robyn E. Elphinstone, Andrea L. Conroy, Michael Hawkes, Laura Hermann, Sophie Namasopo, H. Shaw Warren, Chandy John, W. Conrad Liles, Kevin C. Kain

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background. Malaria remains a major cause of global mortality. Extracellular heme, released during malaria-induced hemolysis, mediates a number of pathogenic processes associated with vascular and organ injury. Hemopexin (hpx) facilitates the degradation of extracellular heme. In this study, we explore the hypothesis that dysregulation of the heme-hpx axis is associated with disease severity, acute kidney injury (AKI), and outcome. Methods. Plasma levels of hemin and hpx (at admission, day 3, and day 14) were assessed in children with severe malaria in Jinja, Uganda. Results. The ratio of heme to hpx was higher at admission and decreased with recovery (median, 0.043 [interquartile range {IQR}, 0.007-0.239] on day 1, 0.024 [IQR, 0.005-0.126] on day 3, and 0.008 [IQR, 0.002-0.022] on day 14; P <. 001). Ratios of heme to hpx at admission were higher in children with as compared to those without severe anemia (median, 0.124 [IQR, 0.024-0.431] vs 0.016 [IQR, 0.003-0.073]; P <. 0001), children with as compared to those without respiratory distress (median, 0.063 [IQR, 0.017-0.413] vs 0.020 [IQR, 0.004-0.124]; P <. 01), and children with as opposed to those without stage 3 AKI (median, 0.354 [IQR, 0.123-2.481] vs 0.037 [IQR, 0.005-0.172], P <. 01). The heme to hpx ratio at admission was associated with 6-month mortality (median, 0.148 [IQR, 0.042-0.500] vs 0.039 [IQR, 0.007-0.172]; P =. 012). Conclusions. The ratio of heme to hpx is associated with disease severity and adverse clinical outcomes in Ugandan children, and dysregulation of the heme axis may contribute to malaria pathogenesis.

Original languageEnglish (US)
Pages (from-to)1268-1275
Number of pages8
JournalJournal of Infectious Diseases
Volume214
Issue number8
DOIs
StatePublished - Oct 15 2016

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Keywords

  • Acute kidney injury
  • Anemia
  • Heme
  • Hemopexin
  • Metabolic acidosis
  • Pediatric
  • Respiratory distress
  • Severe malaria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Elphinstone, R. E., Conroy, A. L., Hawkes, M., Hermann, L., Namasopo, S., Warren, H. S., John, C., Liles, W. C., & Kain, K. C. (2016). Alterations in Systemic Extracellular Heme and Hemopexin Are Associated with Adverse Clinical Outcomes in Ugandan Children with Severe Malaria. Journal of Infectious Diseases, 214(8), 1268-1275. https://doi.org/10.1093/infdis/jiw357