EPO and chronic kidney disease: Some uremic toxins may contribute to anemia in CKD; for example, indoxyl sulfate is a protein-bound uremic toxin that acts in anemia due to impaired EPO synthesis by the kidneys due to a suppression of the EPO gene transcription in a factor hypoxia-inducted factor and promotes suppression of the EPO receptor (EPOR)-AKT pathway [43, 44].