BoneKEy Reports | BoneKEy Watch
Blocking FGF23 has positive and negative effects in renal failure
DOI:10.1038/bonekey.2012.177
Levels of FGF23, a phosphaturic hormone, are characteristically elevated in chronic renal failure: excess FGF23 reduces levels of vitamin D, leading to secondary hyperparathyroidism (HPT), and is associated with higher cardiovascular mortality. In this first study to investigate the effects of an FGF23 neutralizing antibody in a rat model of chronic kidney disease, rats fed a high phosphate diet were treated with different doses of FGF23-Ab or a control isotype antibody.
High dose FGF23-Ab reduced serum phosphate levels more effectively than a low dose. Neutralizing FGF23 had several beneficial effects; serum vitamin D increased, secondary HPT was reduced and normalization of key bone markers, such as trabecular number, cancellous bone volume, bone formation rate and osteoblast and osteoid surface markers, was apparent.
Unfortunately, serum phosphate levels were raised, causing mineral disturbances that increased mortality due to an increase in calcification of the main blood vessels, including the aorta.
Editor's comment: Although markers of bone and mineral metabolism improved, the increase in the degree of aortic calcification led to a higher death rate, probably because the antibody inhibited phosphaturic activity in the kidney tissue that was still able to function. Whether better results would be obtained in rats receiving a reduced phosphate intake remains to be investigated.
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