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Avondt, Kristof van; Nur, Erfan; Zeerleder, Sacha (2019): Mechanisms of haemolysis-induced kidney injury. In: Nature Reviews Nephrology, Vol. 15, No. 11: pp. 671-692
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Intravascular haemolysis is a fundamental feature of chronic hereditary and acquired haemolytic anaemias, including those associated with haemoglobinopathies, complement disorders and infectious diseases such as malaria. Destabilization of red blood cells (RBCs) within the vasculature results in systemic inflammation, vasomotor dysfunction, thrombophilia and proliferative vasculopathy. The haemoprotein scavengers haptoglobin and haemopexin act to limit circulating levels of free haemoglobin, haem and iron - potentially toxic species that are released from injured RBCs. However, these adaptive defence systems can fail owing to ongoing intravascular disintegration of RBCs. Induction of the haem-degrading enzyme haem oxygenase 1 (HO1) - and potentially HO2 - represents a response to, and endogenous defence against, large amounts of cellular haem;however, this system can also become saturated. A frequent adverse consequence of massive and/or chronic haemolysis is kidney injury, which contributes to the morbidity and mortality of chronic haemolytic diseases. Intravascular destruction of RBCs and the resulting accumulation of haemoproteins can induce kidney injury via a number of mechanisms, including oxidative stress and cytotoxicity pathways, through the formation of intratubular casts and through direct as well as indirect proinflammatory effects, the latter via the activation of neutrophils and monocytes. Understanding of the detailed pathophysiology of haemolysis-induced kidney injury offers opportunities for the design and implementation of new therapeutic strategies to counteract the unfavourable and potentially fatal effects of haemolysis on the kidney.