Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study

Ruth Namazzi; Anthony Batte; Robert O. Opoka; Paul Bangirana; Andrew L. Schwaderer; Zachary Berrens; Dibyadyuti Datta; Michael Goings; John M. Ssenkusu; Stuart L. Goldstein; Chandy C. John; Andrea L. Conroy

doi:10.1016/j.eclinm.2022.101292

Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study

Ruth Namazzi, Anthony Batte, Robert O. Opoka, Paul Bangirana, Andrew L. Schwaderer, Zachary Berrens, Dibyadyuti Datta, Michael Goings, John M. Ssenkusu, Stuart L. Goldstein, Chandy C. John, Andrea L. Conroy

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

Abstract

Background: Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. Methods: Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. Findings: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%). Interpretation: Children with severe malaria-associated AKI are at risk of AKD and post-discharge mortality. Funding: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.

Original language	English
Article number	101292
Journal	eClinicalMedicine
Volume	44
DOIs	https://doi.org/10.1016/j.eclinm.2022.101292
Publication status	Published - Feb 2022
Externally published	Yes

Keywords

Acute kidney disease
Acute kidney injury
Blackwater fever
Cerebral malaria
Disability
Malaria
Mortality
Neurologic deficit
NGAL
Sub-Saharan Africa

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.eclinm.2022.101292

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Namazzi, R., Batte, A., Opoka, R. O., Bangirana, P., Schwaderer, A. L., Berrens, Z., Datta, D., Goings, M., Ssenkusu, J. M., Goldstein, S. L., John, C. C., & Conroy, A. L. (2022). Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study. eClinicalMedicine, 44, Article 101292. https://doi.org/10.1016/j.eclinm.2022.101292

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title = "Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study",

abstract = "Background: Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. Methods: Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. Findings: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%). Interpretation: Children with severe malaria-associated AKI are at risk of AKD and post-discharge mortality. Funding: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.",

keywords = "Acute kidney disease, Acute kidney injury, Blackwater fever, Cerebral malaria, Disability, Malaria, Mortality, Neurologic deficit, NGAL, Sub-Saharan Africa",

author = "Ruth Namazzi and Anthony Batte and Opoka, {Robert O.} and Paul Bangirana and Schwaderer, {Andrew L.} and Zachary Berrens and Dibyadyuti Datta and Michael Goings and Ssenkusu, {John M.} and Goldstein, {Stuart L.} and John, {Chandy C.} and Conroy, {Andrea L.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = feb,

doi = "10.1016/j.eclinm.2022.101292",

language = "English",

volume = "44",

journal = "eClinicalMedicine",

issn = "2589-5370",

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Namazzi, R, Batte, A, Opoka, RO, Bangirana, P, Schwaderer, AL, Berrens, Z, Datta, D, Goings, M, Ssenkusu, JM, Goldstein, SL, John, CC & Conroy, AL 2022, 'Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study', eClinicalMedicine, vol. 44, 101292. https://doi.org/10.1016/j.eclinm.2022.101292

TY - JOUR

T1 - Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children

T2 - A prospective cohort study

AU - Namazzi, Ruth

AU - Batte, Anthony

AU - Opoka, Robert O.

AU - Bangirana, Paul

AU - Schwaderer, Andrew L.

AU - Berrens, Zachary

AU - Datta, Dibyadyuti

AU - Goings, Michael

AU - Ssenkusu, John M.

AU - Goldstein, Stuart L.

AU - John, Chandy C.

AU - Conroy, Andrea L.

PY - 2022/2

Y1 - 2022/2

N2 - Background: Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. Methods: Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. Findings: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%). Interpretation: Children with severe malaria-associated AKI are at risk of AKD and post-discharge mortality. Funding: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.

AB - Background: Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. Methods: Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. Findings: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%). Interpretation: Children with severe malaria-associated AKI are at risk of AKD and post-discharge mortality. Funding: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.

KW - Acute kidney disease

KW - Acute kidney injury

KW - Blackwater fever

KW - Cerebral malaria

KW - Disability

KW - Malaria

KW - Mortality

KW - Neurologic deficit

KW - NGAL

KW - Sub-Saharan Africa

UR - http://www.scopus.com/inward/record.url?scp=85124428443&partnerID=8YFLogxK

U2 - 10.1016/j.eclinm.2022.101292

DO - 10.1016/j.eclinm.2022.101292

M3 - Article

AN - SCOPUS:85124428443

SN - 2589-5370

VL - 44

JO - eClinicalMedicine

JF - eClinicalMedicine

M1 - 101292

ER -

Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study

Abstract

Keywords

UN SDGs

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