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Genetic<jats:italic>Hp<\/jats:italic>and\/or<jats:italic>Hpx<\/jats:italic>deletion in mice led to labile heme accumulation in plasma and kidneys, upon<jats:italic>Plasmodium infection<\/jats:italic>. This was associated with higher incidence of mortality and acute kidney injury (AKI) in ageing but not adult<jats:italic>Plasmodium<\/jats:italic>-infected mice, and was corroborated by an inverse correlation between heme and HPX with serological markers of AKI in<jats:italic>P. falciparum<\/jats:italic>malaria. 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