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Review
, 31 (1), 69-77

Pathophysiology, Clinical Presentation, and Treatment of Coma and Acute Kidney Injury Complicating Falciparum Malaria

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Review

Pathophysiology, Clinical Presentation, and Treatment of Coma and Acute Kidney Injury Complicating Falciparum Malaria

Katherine Plewes et al. Curr Opin Infect Dis.

Abstract

Purpose of review: Cerebral impairment and acute kidney injury (AKI) are independent predictors of mortality in both adults and children with severe falciparum malaria. In this review, we present recent advances in understanding the pathophysiology, clinical features, and management of these complications of severe malaria, and discuss future areas of research.

Recent findings: Cerebral malaria and AKI are serious and well recognized complications of severe malaria. Common pathophysiological pathways include impaired microcirculation, due to sequestration of parasitized erythrocytes, systemic inflammatory responses, and endothelial activation. Recent MRI studies show significant brain swelling in both adults and children with evidence of posterior reversible encephalopathy syndrome-like syndrome although targeted interventions including mannitol and dexamethasone are not beneficial. Recent work shows association of cell-free hemoglobin oxidation stress involved in the pathophysiology of AKI in both adults and children. Paracetamol protected renal function likely by inhibiting cell-free-mediated oxidative stress. It is unclear if heme-mediated endothelial activation or oxidative stress is involved in cerebral malaria.

Summary: The direct causes of cerebral and kidney dysfunction remain incompletely understood. Optimal treatment involves prompt diagnosis and effective antimalarial treatment with artesunate. Renal replacement therapy reduces mortality in AKI but delayed diagnosis is an issue.

Figures

FIGURE 1
FIGURE 1
Venn diagrams of mortality of adults and children associated with prognostic manifestations of severe malaria [2,3]. Surface areas represent relative prevalence in severe malaria. Uremia defined as blood urea nitrogen more than 20 mg/dl in children and more than 48 mg/dl in adults. Acidosis defined as base excess less than −8 mmol/l in children and less than −3 mmol/l in adults. Coma score defined as Blantyre Coma Score less than 3 in children and Glasgow Coma Score less than 11 in adults. Reprinted from Tropical Medicine and International Health 19, Supplement 1, World Health Organization, Severe Malaria. Page 16. Copyright (2014).
Box 1
Box 1
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FIGURE 2
FIGURE 2
Malaria retinopathy in a Bangladeshi child with cerebral malaria. (A) Composite fundus photograph. (B) Fluorescein angiogram of same fundus image. Images show widespread retinal whitening and patchy hypoperfusion with a white-centered hemorrhage. Typical malarial retinopathy can include four findings: first, macular (perifoveal) and peripheral retinal whitening, second, retinal vessel whitening/discoloration, third, white-centered hemorrhages, and fourth, papilledema. The former two features (first and second) are specific for malaria and the latter two features (third and fourth) are also found in nonmalarial conditions. Reproduced with permission from BMJ Publishing Group Ltd [97].
FIGURE 3
FIGURE 3
General management of AKI in malaria based on KDIGO guidelines. 1History including preadmission medications, comorbidities, and physical examination focusing on volume status and signs of concomitant sepsis. 2Laboratory tests including serum creatinine, urea, electrolytes, and full blood count. 3Stage using KDIGO staging criteria. If baseline creatinine is unknown, estimate using back-calculation of MDRD equation (>19 years) or Swartz equations (≤18 years). Urinary bladder catheterization to monitor initial urine output if unconscious. If ambulating, urine should be collected to monitor output. Patients should be managed according to AKI stage, as stage correlates with increased morbidity and mortality. 4Daily creatinine and urine output to monitor change in AKI stage severity and guide management. 5Additional investigations to assess AKI etiology: urine analysis, sediment microscopy, creatinine, and sodium; renal ultrasound to assess kidney size, presence of pyelonephritis, and inferior vena cava filling as a gauge of volume status; AKI biomarkers if applicable. Nephrotoxic drugs, that is, aminoglycosides, should be avoided whenever possible. Discontinuation of nephrotoxic drugs may assist with determining AKI etiology. 6If resources permit, monitor hemodynamic variables. Static central venous pressure is of limited value but recommended target is 0 to +5 cmH2O. Arterial pulse pressure as a dynamic variable may be more useful to gauge response to fluid administration. 7Early referral to center with RRT, particularly if one indication for RRT is present. Patients with multiorgan dysfunction are recommended to receive urgent dialysis within 2 h [6]. Patients should be evaluated 3 months after AKI resolution to monitor resolution of kidney function and/or development of chronic kidney disease. AKI, acute kidney injury; KDIGO, Kidney Disease: Improving Global Outcomes; MDRD, modification of diet in renal disease [11]; RRT, renal replacement therapy. Reprinted from Kidney International Supplements 2, Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group, KDIGO Clinical Practice Guideline for Acute Kidney Injury. Page 25. Copyright (2012) with permission from Elsevier.

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References

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