Another explanation is that iron depletion could independently cause GDF-15 induction in the erythroid precursor cells as a result of iron sequestration in macrophages as GDF15 is a product of macrophages activated by pro-inflammatory cytokines that present in excess in CKD, Interestingly CRP induces GDF15 expression through the regulation of p53 binding sites in the GDF15 promoter and they are also relevant markers of inflammation [23]. Here, GDF15 is linked to chronic kidney disease.