Modifiable determinants of ESA hyporesponsiveness are several, the main being iron deficiency; however awareness is now growing on the role of vitamin D. Indeed, across the whole spectrum of CKD, vitamin D deficiency consistently worsens anemia and increases resistance to ESA, while exogenous administration of native and active forms allows improvement of anemia with a reduction of ESA dosing likely due to the antinflammatory and PTH-suppressing properties [62, 71–75]. The gene discussed is PTH; the disease is anemia (phenotype).