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Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges.

ABSTRACT: Acute kidney injury (AKI) is emerging as a complication of increasing clinical importance associated with substantial morbidity and mortality in African children with severe malaria. Using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI, an estimated 24-59% of African children with severe malaria have AKI with most AKI community-acquired. AKI is a risk factor for mortality in pediatric severe malaria with a stepwise increase in mortality across AKI stages. AKI is also a risk factor for post-discharge mortality and is associated with increased long-term risk of neurocognitive impairment and behavioral problems in survivors. Following injury, the kidney undergoes a process of recovery and repair. AKI is an established risk factor for chronic kidney disease and hypertension in survivors and is associated with an increased risk of chronic kidney disease in severe malaria survivors. The magnitude of the risk and contribution of malaria-associated AKI to chronic kidney disease in malaria-endemic areas remains undetermined. Pathways associated with AKI pathogenesis in the context of pediatric severe malaria are not well understood, but there is emerging evidence that immune activation, endothelial dysfunction, and hemolysis-mediated oxidative stress all directly contribute to kidney injury. In this review, we outline the KDIGO bundle of care and highlight how this could be applied in the context of severe malaria to improve kidney perfusion, reduce AKI progression, and improve survival. With increased recognition that AKI in severe malaria is associated with substantial post-discharge morbidity and long-term risk of chronic kidney disease, there is a need to increase AKI recognition through enhanced access to creatinine-based and next-generation biomarker diagnostics. Long-term studies to assess severe malaria-associated AKI's impact on long-term health in malaria-endemic areas are urgently needed.

SUBMITTER: Batte A

PROVIDER: S-EPMC8276826 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAcute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic significance of BWF and AKI are not well understood.MethodsA prospective observational cohort study was conducted to evaluate the association between BWF and AKI in children hospitalized with an acute febrile illness. Secondary objectives were to examine the association of AKI and BWF with (i) host response biomarkers and (ii) mortality. AKI was defined using the Kidney Disease: Improving Global Outcomes criteria and BWF was based on parental report of tea-colored urine. Host markers of immune and endothelial activation were quantified on admission plasma samples. The relationships between BWF and AKI and clinical and biologic factors were evaluated using multivariable regression.ResultsWe evaluated BWF and AKI in 999 children with acute febrile illness (mean age 1.7 years (standard deviation 1.06), 55.7% male). At enrollment, 8.2% of children had a history of BWF, 49.5% had AKI, and 11.1% had severe AKI. A history of BWF was independently associated with 2.18-fold increased odds of AKI (95% CI 1.15 to 4.16). When examining host response, severe AKI was associated with increased immune and endothelial activation (increased CHI3L1, sTNFR1, sTREM-1, IL-8, Angpt-2, sFlt-1) while BWF was predominantly associated with endothelial activation (increased Angpt-2 and sFlt-1, decreased Angpt-1). The presence of severe AKI, not BWF, was associated with increased risk of in-hospital death (RR, 2.17 95% CI 1.01 to 4.64) adjusting for age, sex, and disease severity.ConclusionsBWF is associated with severe AKI in children hospitalized with a severe febrile illness. Increased awareness of AKI in the setting of BWF, and improved access to AKI diagnostics, is needed to reduce disease progression and in-hospital mortality in this high-risk group of children through early implementation of kidney-protective measures.

Project description:Paediatric shock is still a common emergency of public health importance with an estimated 400,000-500,000 reported cases annually. Mortality due to paediatric shock has varied over the years. Data in 1980s show that mortality rates due to septic shock in children were over 50%; but by the end of the year 2000 data indicated that though a marked decline in mortality rates had been achieved, it had stagnated at about 20%. Descriptions of paediatric shock reveal the lack of a common definition and there are important gaps in evidence-based management in different settings. In well-resourced healthcare systems with well-functioning intensive care facilities, the widespread implementation of shock management guidelines based on the Paediatric Advanced Life Support and European Paediatric Advanced Life Support courses have reduced mortality. In resource limited settings with diverse infectious causative agents, the Emergency Triage Assessment and Treatment (ETAT) approach is more pragmatic, but its impact remains circumscribed to centres where ETAT has been implemented and sustained. Advocacy for common management pathways irrespective of underlying cause have been suggested. However, in sub Saharan Africa, the diversity of underlying causative organisms and patient phenotypes may limit a single approach to shock management. Data from a large fluid trial (the FEAST trial) in East Africa have provided vital insight to shock management. In this trial febrile children with clinical features of impaired perfusion were studied. Rapid infusion of fluid boluses, irrespective of whether the fluid was colloid or crystalloid, when compared to maintenance fluids alone had an increased risk of mortality at 48 h. All study participants were promptly managed for underlying conditions and comorbidity such as malaria, bacteraemia, severe anaemia, meningitis, pneumonia, convulsions, hypoglycaemia and others. The overall low mortality in the trial suggests the potential contribution of ETAT, the improved standard of care and supportive treatment across the subgroups in the trial. Strengthening systems that enable rapid identification of shock, prompt treatment of children with correct antimicrobials and supportive care such as oxygen administration and blood transfusion may contribute to better survival outcomes in resources limited settings.

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Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges.

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