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

Chenchen Zhou; Changlin Mei; Bing Dai; Cheng Xue

doi:10.1681/ASN.2018050517

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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.

Disclosures

None.

Acknowledgments

The work was supported by National Natural Science Foundation of China grant 81700579.

Footnotes

Published online ahead of print. Publication date available at www.jasn.org.

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