Identifying prognostic factors of severe metabolic acidosis and uraemia in African children with severe falciparum malaria: a secondary analysis of a randomized trial

Abstract

Background Severe metabolic acidosis and acute kidney injury are major causes of mortality in children with severe malaria but are often underdiagnosed in low resource settings. Methods A retrospective analysis of the ‘Artesunate versus quinine in the treatment of severe falciparum malaria in African children’ (AQUAMAT) trial was conducted to identify clinical features of severe metabolic acidosis and uraemia in 5425 children from nine African countries. Separate models were fitted for uraemia and severe metabolic acidosis. Separate univariable and multivariable logistic regression were performed to identify prognostic factors for severe metabolic acidosis and uraemia. Both analyses adjusted for the trial arm. A forward selection approach was used for model building of the logistic models and a threshold of 5% statistical significance was used for inclusion of variables into the final logistic model. Model performance was assessed through calibration, discrimination, and internal validation with bootstrapping. Results There were 2296 children identified with severe metabolic acidosis and 1110 with uraemia. Prognostic features of severe metabolic acidosis among them were deep breathing (OR: 3.94, CI 2.51–6.2), hypoglycaemia (OR: 5.16, CI 2.74–9.75), coma (OR: 1.72 CI 1.17–2.51), respiratory distress (OR: 1.46, CI 1.02–2.1) and prostration (OR: 1.88 CI 1.35–2.59). Features associated with uraemia were coma (3.18, CI 2.36–4.27), Prostration (OR: 1.78 CI 1.37–2.30), decompensated shock (OR: 1.89, CI 1.31–2.74), black water fever (CI 1.58. CI 1.09–2.27), jaundice (OR: 3.46 CI 2.21–5.43), severe anaemia (OR: 1.77, CI 1.36–2.29) and hypoglycaemia (OR: 2.77, CI 2.22–3.46) Conclusion Clinical and laboratory parameters representing contributors and consequences of severe metabolic acidosis and uraemia were independently associated with these outcomes. The model can be useful for identifying patients at high risk of these complications where laboratory assessments are not routinely available.

The Effect of Arthrospira platensis (Phormidiaceae) on the Acute Toxicity of Artemeter Lumefantrine in Malaria Patients

“…Among complications that are associated with falciparum malaria, renal and hepatic dysfunctions are common in both children and adults living in malaria endemic regions [27]. Hepatic dysfunction is a well-known feature of severe malaria, contributing to clinically significant complications such as hypoglycaemia, metabolic acidosis, impaired drug metabolism, and finally organ failure [28]. Malaria-associated liver damage in uncomplicated malaria, however, has rarely been investigated so far.…”

Diagnosis and management of malaria in the intensive care unit

“…Histopathological features of malaria-related AKI include acute tubular necrosis and sometimes interstitial nephritis and glomerulonephritis. [ [186] , [187] , [188] ] The prevalence of AKI was recently reported to range from 20% to 40% among adults and children with severe malaria, with some studies reporting an AKI incidence of 59% in children. [ 187 ] Therefore, it is necessary to ensure that all patients diagnosed with severe malaria are screened for AKI.…”

“…[ [186] , [187] , [188] ] The prevalence of AKI was recently reported to range from 20% to 40% among adults and children with severe malaria, with some studies reporting an AKI incidence of 59% in children. [ 187 ] Therefore, it is necessary to ensure that all patients diagnosed with severe malaria are screened for AKI. Management is largely supportive and involves maintaining optimal fluid and electrolyte balance (for patients with pre-renal causes) and renal replacement therapy – hemodialysis or peritoneal dialysis – where indicated.…”

“…[ 20 ] The prognosis for malaria-related AKI is good as it resolves in days to weeks, although 5% of patients with severe malaria develop chronic kidney disease. [ 187 ]…”

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis

“…Acute kidney injury is defined as an abrupt loss of kidney excretory function and is diagnosed by an accumulation of nitrogenous waste products associated with reduced glomerular filtration and/or reduced urine output ( Kellum et al, 2021 ). Two nitrogenous waste products commonly used to assess kidney function in severe malaria include creatinine, which is used to define AKI based on international consensus guidelines, and blood urea nitrogen (BUN), a less specific indicator of renal impairment ( World Health Organization [WHO], 2014 ; Mzumara et al, 2021 ). AKI and BUN were independent clinical risk factors for neurologic deficits in a recent cohort of children with severe malaria ( Namazzi et al, 2022a ).…”