Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality

Andrea L. Conroy, Michael Hawkes, Robyn E. Elphinstone, Catherine Morgan, Laura Hermann, Kevin R. Barker, Sophie Namasopo, Robert O. Opoka, Chandy John, W. Conrad Liles, Kevin C. Kain

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented.Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay.Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-95; P = .006) and 0.72 (95% CI, .57-87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively).Conclusions. Acute kidney injury is an underrecognized complication in young children with SM and is associated with increased mortality.

Original languageEnglish (US)
Article numberofw046
JournalOpen Forum Infectious Diseases
Volume3
Issue number2
DOIs
StatePublished - Apr 1 2016

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Acute Kidney Injury
Malaria
Pediatrics
Mortality
Cystatin C
Nitric Oxide
Blood Urea Nitrogen
Placebos
Kidney Diseases
Confidence Intervals
Creatinine
Kidney
Uganda
Area Under Curve
Hospitalization
Biomarkers
Enzyme-Linked Immunosorbent Assay

Keywords

  • Acute kidney injury
  • Children
  • Creatinine
  • Inhaled nitric oxide
  • Severe malaria

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

Conroy, A. L., Hawkes, M., Elphinstone, R. E., Morgan, C., Hermann, L., Barker, K. R., ... Kain, K. C. (2016). Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality. Open Forum Infectious Diseases, 3(2), [ofw046]. https://doi.org/10.1093/ofid/ofw046

Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality. / Conroy, Andrea L.; Hawkes, Michael; Elphinstone, Robyn E.; Morgan, Catherine; Hermann, Laura; Barker, Kevin R.; Namasopo, Sophie; Opoka, Robert O.; John, Chandy; Liles, W. Conrad; Kain, Kevin C.

In: Open Forum Infectious Diseases, Vol. 3, No. 2, ofw046, 01.04.2016.

Research output: Contribution to journalArticle

Conroy, AL, Hawkes, M, Elphinstone, RE, Morgan, C, Hermann, L, Barker, KR, Namasopo, S, Opoka, RO, John, C, Liles, WC & Kain, KC 2016, 'Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality', Open Forum Infectious Diseases, vol. 3, no. 2, ofw046. https://doi.org/10.1093/ofid/ofw046
Conroy, Andrea L. ; Hawkes, Michael ; Elphinstone, Robyn E. ; Morgan, Catherine ; Hermann, Laura ; Barker, Kevin R. ; Namasopo, Sophie ; Opoka, Robert O. ; John, Chandy ; Liles, W. Conrad ; Kain, Kevin C. / Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality. In: Open Forum Infectious Diseases. 2016 ; Vol. 3, No. 2.
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abstract = "Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented.Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay.Results. Eighty-one (45.5{\%}) children had KDIGO-defined AKI in the study: 42 (51.9{\%}) stage 1, 18 (22.2{\%}) stage 2, and 21 (25.9{\%}) stage 3. Acute kidney injury evolved or developed in 50{\%} of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0{\%}) of children in the iNO arm developing AKI compared with 34 (37.4{\%}) in the placebo arm (relative risk, 1.36; 95{\%} confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25{\%} in children with AKI vs 1.9{\%} in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5{\%} in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95{\%} CI, .65-95; P = .006) and 0.72 (95{\%} CI, .57-87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively).Conclusions. Acute kidney injury is an underrecognized complication in young children with SM and is associated with increased mortality.",
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T1 - Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality

AU - Conroy, Andrea L.

AU - Hawkes, Michael

AU - Elphinstone, Robyn E.

AU - Morgan, Catherine

AU - Hermann, Laura

AU - Barker, Kevin R.

AU - Namasopo, Sophie

AU - Opoka, Robert O.

AU - John, Chandy

AU - Liles, W. Conrad

AU - Kain, Kevin C.

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N2 - Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented.Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay.Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-95; P = .006) and 0.72 (95% CI, .57-87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively).Conclusions. Acute kidney injury is an underrecognized complication in young children with SM and is associated with increased mortality.

AB - Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented.Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay.Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-95; P = .006) and 0.72 (95% CI, .57-87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively).Conclusions. Acute kidney injury is an underrecognized complication in young children with SM and is associated with increased mortality.

KW - Acute kidney injury

KW - Children

KW - Creatinine

KW - Inhaled nitric oxide

KW - Severe malaria

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