File:Malarial nephropathy.webp

English: Figure 1 Interactions between P. falciparum malaria-specific pathology and the systemic inflammatory response in malaria-related acute kidney injury. The causative agents of malaria are protozoan parasites belonging to the Plasmodium genus, which includes multiple species, five of which regularly infect humans: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi (4). A bite by a Plasmodium spp.-infected mosquito (1) leads to the injection of motile sporozoites within the host, which travel through the lymphatics and blood until they reach the liver and invade hepatocytes (2). Once inside the hepatocyte, each sporozoite replicates and gives rise to thousands of merozoites, which are released into the bloodstream (3) when the infected hepatocyte bursts. Free merozoites then proceed to infect red blood cells (RBCs) within the bloodstream (4) and enter their asexual reproductive cycle, also referred to as the intraerythrocytic cycle. This developmental stage is characterized by a replication cycle that typically lasts approximately 48 hours and which culminates in the simultaneous rupturing of the parasitized RBCs (pRBCs), and the release of a massive number of merozoites into the bloodstream, which go on to infect further RBCs. Malaria is associated with a vigorous inflammatory response, which shares some features with other infectious diseases, but it is accompanied by unique aspects of pathophysiology that exacerbate the impact of systemic inflammation on individual organs. These unique aspects include the cytoadherence of parasite-infected red blood cells (pRBCs) to the microvascular endothelium, and the extensive release of cell free hemoglobin and heme during hemolysis. Although the exact pathophysiology of AKI in severe malaria remains unknown, we propose that the sequestration of parasitized red blood cells, rosetting and accumulation of parasite products in the kidney, resulting in endothelial activation and microvascular obstruction, promote the already damaging effects of an exuberant inflammatory response and heme-mediated oxidative damage. DAMP, Damage-associated molecular pattern; PAMP, Pathogen-associated molecular pattern.