Evaluating the renoprotective effect of acetaminophen in children with severe falciparum malaria

Acute kidney injury (AKI) complicating critical illness is an important problem, contributing to roughly 1.7 million deaths worldwide per year. Treatment is limited to dialysis, which is costly and frequently unavailable. Preventing AKI is a critical step to reduce deaths. Acetaminophen (Tylenol) has the potential to reduce AKI caused by oxidative damage from hemoglobin (released from red blood cells) and myoglobin (released from muscle cells). Acetaminophen inhibits this oxidative damage and reduces kidney dysfunction in animal models, and in patients after cardiac surgery or in patients with sepsis.

I previously led a trial in adults with severe malaria showing that acetaminophen improved kidney function and reduced the odds of developing AKI. Since children bear the major burden of malaria, it is crucial to test this protective effect in African children where 45% of patients have AKI. The goal is to assess the role of acetaminophen as a kidney protective therapy in severe malaria.

I will conduct a randomized controlled trial of adjunctive acetaminophen in African children with severe malaria. If the trial is positive, the results would change severe malaria management globally. It could be rapidly scalable as acetaminophen is inexpensive, safe and widely used. These findings will have broad implications for other major causes of hemoprotein-mediated AKI including crush injury and sepsis, which directly impact thousands of Canadians.