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Erythropoiesis and chronic kidney disease–related anemia: From physiology to new therapeutic advancements
Author(s) -
Cernaro Valeria,
Coppolino Giuseppe,
Visconti Luca,
Rivoli Laura,
Lacquaniti Antonio,
Santoro Domenico,
Buemi Antoine,
Loddo Saverio,
Buemi Michele
Publication year - 2019
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21527
Subject(s) - erythropoiesis , erythropoietin , anemia , bone marrow , medicine , hypoxia (environmental) , kidney disease , ineffective erythropoiesis , kidney , immunology , endocrinology , chemistry , organic chemistry , oxygen
Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia‐inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in‐depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis‐stimulating agents.