Sunday, July 8, 2018
Topic Discussion: FGF-23- friend of foe?
FGF-23 has a been a molecule that has really starting changing the way we have thought of bone mineral disease in Nephrology. There have been some observational studies showing that higher the FGF-23 level, the worse the renal and cardiac outcomes in CKD and ESRD patients.
Two studies I stumbled on twitter world shocked me.
The first was the 2012 JCI paper that showed FGF-23 neutralization improves CKD-associated hyperparathyroidism yet increases mortality. While this was an animal study, it showed that reducing FGF-23 was not a good thing. To determine the role of FGF-23, and role on CKD-MBD and secondary hyperparathyroidism, the authors developed a monoclonal antibody against FGF-23 to evaluated the impact of chronic FGF-23 neutralization on CKD-MBD and associated morbidities in a rat model of CKD-MBD. CKD-MBD rates were fed a high phosphate diet and treated with low and high doses of the antibody or an isotype control of the antibody. Neutralization of FGF-23 led to reduction of PTH, increased vitamin D levels and calcium level and normalization of bone markers. But they also observed dose dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with the FGF-23-ab.
Interesting, the monoclonal antibody to FGF-23 has been now clinically used in X linked hypophosphatemia recently published in NEJM
The second study is a recent JASN meta-analysis of prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. The increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure-response relationship, suggested that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.
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