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Erythropoietin produced in the kidneys are the major stimulant of red blood cell (RBC) production as a response to anemia. Erythropoietin is stimulated by tissue hypoxia, that in turn stimulates erythroid progenitor cells to proliferate. The EPO levels follow a reverse relationship with the hemoglobin levels. Thus, in normal hosts, low levels of hemoglobin are associated with high levels of EPO. However, in patients with chronic kidney disease and anemia of chronic diseases the response may not be as strong as seen in patients without these comorbidities.