Mechanisms of haemolysis-induced kidney injury.

Van Avondt, Kristof; Nur, Erfan; Zeerleder, Sacha Sergio (2019). Mechanisms of haemolysis-induced kidney injury. Nature reviews. Nephrology, 15(11), pp. 671-692. Nature Publishing Group 10.1038/s41581-019-0181-0

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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.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Zeerleder, Sacha Sergio

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1759-507X

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

13 Nov 2019 16:22

Last Modified:

13 Nov 2019 16:22

Publisher DOI:

10.1038/s41581-019-0181-0

PubMed ID:

31455889

BORIS DOI:

10.7892/boris.133392

URI:

https://boris.unibe.ch/id/eprint/133392

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