TY - JOUR
T1 - Pathophysiology of Acute Kidney Injury in Malaria and Non-Malarial Febrile Illness
T2 - A Prospective Cohort Study
AU - Hawkes, Michael T.
AU - Leligdowicz, Aleksandra
AU - Batte, Anthony
AU - Situma, Geoffrey
AU - Zhong, Kathleen
AU - Namasopo, Sophie
AU - Opoka, Robert O.
AU - Kain, Kevin C.
AU - Conroy, Andrea L.
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4
Y1 - 2022/4
N2 - Acute kidney injury (AKI) is a life-threatening complication. Malaria and sepsis are leading causes of AKI in low-and-middle-income countries, but its etiology and pathogenesis are poorly understood. A prospective observational cohort study was conducted to evaluate pathways of immune and endothelial activation in children hospitalized with an acute febrile illness in Uganda. The relationship between clinical outcome and AKI, defined using the Kidney Disease: Improving Global Outcomes criteria, was investigated. The study included 967 participants (mean age 1.67 years, 44.7% female) with 687 (71.0%) positive for malaria by rapid diagnostic test and 280 (29.1%) children had a non-malarial febrile illness (NMFI). The frequency of AKI was higher in children with NMFI compared to malaria (AKI, 55.0% vs. 46.7%, p = 0.02). However, the frequency of severe AKI (stage 2 or 3 AKI) was comparable (12.1% vs. 10.5%, p = 0.45). Circulating markers of both immune and endothelial activation were associated with severe AKI. Children who had malaria and AKI had increased mortality (no AKI, 0.8% vs. AKI, 4.1%, p = 0.005), while there was no difference in mortality among children with NMFI (no AKI, 4.0% vs. AKI, 4.6%, p = 0.81). AKI is a common complication in children hospitalized with acute infections. Immune and endothelial activation appear to play central roles in the pathogenesis of AKI.
AB - Acute kidney injury (AKI) is a life-threatening complication. Malaria and sepsis are leading causes of AKI in low-and-middle-income countries, but its etiology and pathogenesis are poorly understood. A prospective observational cohort study was conducted to evaluate pathways of immune and endothelial activation in children hospitalized with an acute febrile illness in Uganda. The relationship between clinical outcome and AKI, defined using the Kidney Disease: Improving Global Outcomes criteria, was investigated. The study included 967 participants (mean age 1.67 years, 44.7% female) with 687 (71.0%) positive for malaria by rapid diagnostic test and 280 (29.1%) children had a non-malarial febrile illness (NMFI). The frequency of AKI was higher in children with NMFI compared to malaria (AKI, 55.0% vs. 46.7%, p = 0.02). However, the frequency of severe AKI (stage 2 or 3 AKI) was comparable (12.1% vs. 10.5%, p = 0.45). Circulating markers of both immune and endothelial activation were associated with severe AKI. Children who had malaria and AKI had increased mortality (no AKI, 0.8% vs. AKI, 4.1%, p = 0.005), while there was no difference in mortality among children with NMFI (no AKI, 4.0% vs. AKI, 4.6%, p = 0.81). AKI is a common complication in children hospitalized with acute infections. Immune and endothelial activation appear to play central roles in the pathogenesis of AKI.
KW - acute infection
KW - acute kidney injury
KW - children
KW - endothelial activation
KW - immune activation
KW - malaria
KW - mortality
KW - non-malarial febrile illness
KW - sepsis
KW - sub-Saharan Africa
UR - http://www.scopus.com/inward/record.url?scp=85128618879&partnerID=8YFLogxK
U2 - 10.3390/pathogens11040436
DO - 10.3390/pathogens11040436
M3 - Article
AN - SCOPUS:85128618879
SN - 2076-0817
VL - 11
JO - Pathogens
JF - Pathogens
IS - 4
M1 - 436
ER -
