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

11 Citations (Scopus)

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

Fingerprint

Hemopexin
Heme
Malaria
Acute Kidney Injury
Hemin
Uganda
Mortality
Vascular System Injuries
Hemolysis
Anemia

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

Alterations in Systemic Extracellular Heme and Hemopexin Are Associated with Adverse Clinical Outcomes in Ugandan Children with Severe Malaria. / Elphinstone, Robyn E.; Conroy, Andrea L.; Hawkes, Michael; Hermann, Laura; Namasopo, Sophie; Warren, H. Shaw; John, Chandy; Liles, W. Conrad; Kain, Kevin C.

In: Journal of Infectious Diseases, Vol. 214, No. 8, 15.10.2016, p. 1268-1275.

Research output: Contribution to journalArticle

Elphinstone, Robyn E. ; Conroy, Andrea L. ; Hawkes, Michael ; Hermann, Laura ; Namasopo, Sophie ; Warren, H. Shaw ; John, Chandy ; Liles, W. Conrad ; Kain, Kevin C. / Alterations in Systemic Extracellular Heme and Hemopexin Are Associated with Adverse Clinical Outcomes in Ugandan Children with Severe Malaria. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 8. pp. 1268-1275.
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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.",
keywords = "Acute kidney injury, Anemia, Heme, Hemopexin, Metabolic acidosis, Pediatric, Respiratory distress, Severe malaria",
author = "Elphinstone, {Robyn E.} and Conroy, {Andrea L.} and Michael Hawkes and Laura Hermann and Sophie Namasopo and Warren, {H. Shaw} and Chandy John and Liles, {W. Conrad} and Kain, {Kevin C.}",
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T1 - Alterations in Systemic Extracellular Heme and Hemopexin Are Associated with Adverse Clinical Outcomes in Ugandan Children with Severe Malaria

AU - Elphinstone, Robyn E.

AU - Conroy, Andrea L.

AU - Hawkes, Michael

AU - Hermann, Laura

AU - Namasopo, Sophie

AU - Warren, H. Shaw

AU - John, Chandy

AU - Liles, W. Conrad

AU - Kain, Kevin C.

PY - 2016/10/15

Y1 - 2016/10/15

N2 - 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.

AB - 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.

KW - Acute kidney injury

KW - Anemia

KW - Heme

KW - Hemopexin

KW - Metabolic acidosis

KW - Pediatric

KW - Respiratory distress

KW - Severe malaria

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