SCM12: PTH and FGF-23

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!

Comments

  1. Mostapha Habib Allah says:

    I think, parathyroid receptors of FGF23 become resistant or less expressed

  2. Ezra hazzan says:

    Although FGF-23 is extremely high and this should decrease the level of PTH, there are other stimulators of PTH in esrd. Low vitamin d and low calcium are some examples. Hyperphosphatemia is extremely a potent activator of the parathyroid glad to produce PTH. There are some animal studies which identified a receptor of phos in the parathyroid gland, however this is not confirmed in human. FGF-23 itself decrease the conversion of 1-25 hyroxy bit d ( like phos) and stimulate PTH. So although FGF-23 directly inhibits PTH, it stimulates its production indirectly. Added to that other factors as mentioned above

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  1. [...] PTH and FGF-23 Clinical Assessment of Bone Mineral Status Share this:ShareEmailPrintFacebookTwitterDiggRedditLinkedInStumbleUponLike this:LikeBe the first to like this post. Filed Under: NKF 2012 Spring Clinical Meetings Tagged With: Desai, NKF2012, SCM12 « SCM12: Therapeutics in post surgical AKI [...]

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