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

Anthony Batte; Zachary Berrens; Kristin Murphy; Ivan Mufumba; Maithri L Sarangam; Michael T Hawkes; Andrea L Conroy

doi:10.2147/IJNRD.S239157

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

Int J Nephrol Renovasc Dis. 2021 Jul 8:14:235-253. doi: 10.2147/IJNRD.S239157. eCollection 2021.

Authors

Anthony Batte¹, Zachary Berrens², Kristin Murphy³, Ivan Mufumba⁴, Maithri L Sarangam⁵, Michael T Hawkes⁶, Andrea L Conroy³

Affiliations

¹ Child Health and Development Centre, Makerere University College of Health Sciences, Kampala, Uganda.
² Department of Pediatrics, Pediatric Critical Care Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
³ Department of Pediatrics, Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ CHILD Research Laboratory, Global Health Uganda, Kampala, Uganda.
⁵ Department of Global Health, University of Washington, Seattle, WA, USA.
⁶ Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

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.

Keywords: acute kidney injury; children; chronic kidney disease; creatinine; endothelial activation; hypertension; hypovolemia; malaria; mortality; pathophysiology; prevalence; proteinuria; sub-Saharan Africa; treatment.

Publication types

Review