Fibroblast growth factor 23: friend or foe in uremia?

Uremia is a complex metabolic state marked by derangement of many signaling molecules and metabolic intermediates; of these, the massively increased levels of FGF23 are among the most striking. It has remained unclear whether FGF23 is directly implicated in the pathogenesis of chronic kidney disease (CKD) and its complications, a consequence of other dysregulated pathways, or perhaps an adaptive - and thus desirable - response. In this issue of the JCI, Shalhoub et al. describe the chronic effects of antibody-mediated FGF23 neutralization in a CKD mouse model, shedding new light on this complicated story and moving us one step closer to understanding the role of FGF23 in CKD.