We show that excess LCN2 in CKD contributes to excess circulating FGF23, development of cardiac disease, and premature death, and that genetic ablation of Lcn2 in CKD partially reduces Fgf23 bone mRNA expression, circulating FGF23 levels and results in marked improvement in cardiac function and lifespan. The gene discussed is FGF23; the disease is chronic kidney disease.