KL and anemia (phenotype): Recent studies demonstrate that the cardiac hypertrophy often observed in CKD patients is associated with FGF23 effects via Klotho-independent mechanisms in heart.27,28 In the Chronic Renal Insufficiency Cohort (CRIC) trial, it was shown that heart failure and mortality is primarily driven by anemia-dependent FGF23 production.29 Collectively, these findings underscore that FGF23 production in osteocytes is highly responsive to hypoxia/anemia, which may lead to disease manifestations.