Fibroblast Growth Factor-23 May Follow Cardiovascular Disease Rather than Causing It in Chronic Kidney Disease

• cardiovascular disease
• fibroblast
• chronic kidney disease

We read the article “Fibroblast growth factor-23 and risks of cardiovascular and noncardiovascular diseases: A meta-analysis” by Marthi et al.¹ with great interest. The study provided an important demonstration that serum higher fibroblast growth factor-23 (FGF-23) level was positively associated with cardiovascular and noncardiovascular outcomes in populations with or without CKD.¹ In agreement with Marthi et al.,¹ our previous meta-analysis also pointed out that there might be predictive effects of FGF-23 on cardiovascular diseases (CVDs; including myocardial infarction, atrial fibrillation, myocardial ischemia, heart failure, and stroke) and mortality in patients with CKD.²

However, the absence of an exposure-response relationship and similarly sized associations between FGF-23 and different outcomes may not be strong enough to suggest a noncausal relationship between FGF-23 and CVD. Indeed, interactions between FGF-23 and CVD are complicated and remain inconclusive. Experimental studies have revealed that FGF-23 could induce left ventricular hypertrophy.³ Both FGF-23 overexpression and Klotho deficiency showed cardiac remodeling effects in CKD.⁴ However, Slavic et al.⁵ found that genetic ablation of FGF-23 or Klotho did not modulate heart hypertrophy, indicating other mediators as the real culprits. Recently, left ventricular hypertrophy in transgenic mice was found to elevate myocardial and serum levels of FGF-23.³ Taken together, the mutual promotion between FGF-23 and CVD indicates a complex interaction between mineral metabolism and the cardiovascular system in CKD. FGF-23 may follow CVD rather than causing it in CKD.

In conclusion, the finding of this meta-analysis¹ is very important, because it brings us a deep and broad view of FGF-23 in CVD and mortality in patients with or without kidney disease. More mechanisms between FGF-23 and CVD will need to be studied to better understand the effect of FGF-23 on cardiovascular health in patients with CKD.

• Copyright © 2018 by the American Society of Nephrology