PTH and FGF-23
Myles Wolf, MD (University of Miami)
Many of us have been hearing a lot about the newest player in CKD-BMD, FGF-23. Dr. Wolf set the record straight about what we know and don’t know about this newcomer.
To start, FGF-23 had been identified as early as 11-12 years ago. Through a series of keen observations in patients with genetic mutations, scientists concluded that FGF-23 may have a role in bone mineral disease. Today, we know that FGF-23 is produced by osteoclasts (though there is speculation that other sites of production exist but have yet to be identified). FGF-23 participates in elegant neuro-endocrine feedback loops (which can best be described by viewing the loop – see our Tweet). Both 1,25 vitamin D and iPTH stimulate production of FGF-23, and it in turn inhibits production of both (more on this later).
Dr. Wolf showed animal data that FGF-23 has direct deleterious effects on left ventricle morphology. In animals that have overexpression of FGF-23, LVH is significantly more likely to occur. In those same animals that are now given an antibody against FGF-23, LVH regresses. This is important as FGF-23 levels steadily increase in CKD patients (the highest levels seen in ESRD).
As of yet, scientists still don’t have a handle on what the “normal” FGF-23 level ought to be. However, FGF-23 levels seem to rise much earlier in CKD than either PTH or phosphorous. While the latter 2 rise in patients with eGFRs < 50, FGF-23 is seen elevated in patients as early as eGFRs of 60-70 (this interpretation presumes a “normal” FGF-23 level, which is, as of yet, not established).
Finally, FGF-23 is associated with more than just LVH, but also mortality. In fact, early data show a stronger correlation between mortality and FGF-23 than either PTH or phosphorous!
Question: Why do PTH levels remain elevated in dialysis patients when their FGF-23 levels are at their highest? If you know the answer, comment below.
Check back for more eAJKD coverage of SCM12! Also, check out @eAJKD on Twitter for updates of SCM12!