Effect of Paracetamol on Renal Function in Plasmodium Knowlesi Malaria
Status:
Completed
Trial end date:
2018-02-01
Target enrollment:
Participant gender:
Summary
Acute kidney injury is a common complication of severe Plasmodium knowlesi malaria, and an
important contributor to mortality.
The exact pathogenic mechanisms of AKI in knowlesi malaria are not known, however it is
hypothesised that haemolysis of red blood cells and subsequent release of cell-free
haemoglobin leads to oxidative stress and lipid peroxidation in the renal tubules.
A novel mechanism of paracetamol was recently demonstrated, showing that paracetamol acts as
a potent inhibitor of hemoprotein-catalyzed lipid peroxidation. In a proof of concept trial,
paracetamol at therapeutic levels was shown to significantly decrease oxidative kidney injury
and improve renal function by inhibiting the hemoprotein-catalyzed lipid peroxidation in a
rat model of rhabdomyolysis-induced renal injury.
The investigators hypothesize that this novel inhibitory mechanism of paracetamol may provide
renal protection in adults with knowlesi malaria by reducing the hemoprotein-induced lipid
peroxidation that occurs in haemolytic conditions. As there is currently no consensus that
exists concerning adequate medical treatment for severe malaria complicated by intravascular
haemolysis and AKI, the potential application of paracetamol would be of benefit, especially
as it is safe and widely available.