Although PHD inhibitors (e.g., roxaduxat) have been considered in the treatment of CKD-related anemia, their action may be partly neutralized, however, as CKD progression proceeds, since the HIF-2α and EPO encoding gene promoter regions are hypermethylated and therefore epigenetically silenced in MF-REPs, thus hampering the expression of these genes [7]. The gene discussed is EPAS1; the disease is anemia (phenotype).