Role of Klotho and Fibroblast Growth Factor 23 in Arterial Calcification, Thickness, and Stiffness: a Meta-analysis of Observational Studies

This meta-analysis was conducted to clarify the role of klotho and fibroblast growth factor 23 (FGF-23) in human arterial remodeling across recent studies, in terms of arterial calcification, thickness, and stiffness. A systematic literature search was conducted on five databases for articles up to December 2023. Arterial calcification, thickness, and stiffness were determined using the calcification score and artery affected, carotid intima-media thickness (CIMT), and pulse wave velocity (PWV), respectively. Sixty-two studies with a total of 27,459 individuals were included in this meta-analysis. Most studies involved chronic kidney disease patients. Study designs were mostly cross-sectional with only one case-control and nine cohorts. FGF-23 was positively correlated with arterial calcification (r = 0.446 [0.254-0.611], p < 0.0001 and aOR = 1.36 [1.09-1.69], p = 0.006), CIMT (r = 0.188 [0.02-0.354], p = 0.03), and PWV (r = 0.235 [0.159-0.310], p < 0.00001). By contrast, Klotho was inversely correlated with arterial calcification (r = - 0.388 [- 0.578 to - 0.159], p = 0.001) and CIMT (r = - 0.38 [- 0.53 to - 0.207], p < 0.00001). In conclusion, FGF-23 and Klotho were associated with arterial calcification, thickness, and stiffness, clarifying their role in arterial remodeling processes.