Concept Maps: Bone disease, FGF-23 and more..

 

references

https://www.kidney-international.org/article/S0085-2538(15)54255-5/fulltext

https://jasn.asnjournals.org/content/18/3/875

Special post by 

Lakshmi Kannan, MBBS, MD, 

Department of Nephrology, Pikeville Medical Center

Adjunct Faculty, University of Pikeville Kentucky College of Osteopathic Medicine

Kentucky, USA

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.

IS CKD-MBD a syndrome?

 

Is it a syndrome? An article in NDT addresses this entity as a possible syndrome in CKD

When one looks at nephrotic syndrome or metabolic syndrome, those entities usually fulfill the criteria for calling it a “syndrome” as most patients would fit that criteria and prognosis and treatment would be resulted.  In CKD-MBD, this article argues against it being a potential syndrome in CKD but perhaps might be.  CKD-MBD represents a synopsis of three closely related disease conditions: laboratory abnormalities indicative of disturbed bone and mineral metabolism; renal osteodystrophy summarizing the variety of bone lesion subtypes occurring in CKD; cardiovascular disease representing accelerated arteriosclerosis, left ventricular hypertrophy and a variety of additional pathologies in the vasculature and the heart in patients with CKD.

But do all patients with CKD have all the bone parameters abnormal; and if they do, what is the CVD risk and prognosis?  But it’s worth some thought of this potentially being a syndrome.

Have a look at the full paper.

http://m.ndt.oxfordjournals.org/content/29/10/1815.full.pdf
A workshop is being held in Europe to further define this