AUTHOR=Liu QiFeng , Yu LiXia , Yin XiaoYa , Ye JianMing , Li ShaSha 

TITLE=Correlation Between Soluble Klotho and Vascular Calcification in Chronic Kidney Disease: A Meta-Analysis and Systematic Review

JOURNAL=Frontiers in Physiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.711904

DOI=10.3389/fphys.2021.711904

ISSN=1664-042X

ABSTRACT=<p><bold>Background:</bold> The correlation between soluble Klotho (sKlotho) level and vascular calcification (VC) in patients with chronic kidney disease (CKD) remains controversial. Using meta-analysis, we aimed to address this controversy and assess the feasibility of applying sKlotho as a biomarker for VC.</p><p><bold>Methods:</bold> Medical electronic databases were thoroughly searched for eligible publications on the association between sKlotho level and VC in CKD patients. Effectors, including correlation coefficients (<italic>r</italic>), odds ratios (ORs), hazard ratio (HR) or β-values, and 95% confidence intervals (CIs) were extracted and combined according to study design or effector calculation method. Pooled effectors were generated using both random-effects models and fixed-effects models according to <italic>I</italic><sup>2</sup>-value. Origin of heterogeneity was explored by sensitivity analysis and subgroup analysis.</p><p><bold>Results:</bold> Ten studies with 1,204 participants from a total of 1,199 publications were eligible and included in this meta-analysis. The combined correlation coefficient (<italic>r</italic>) was [−0.33 (−0.62, −0.04)] with significant heterogeneity (<italic>I</italic><sup>2</sup> = 89%, <italic>p</italic> &lt; 0.001) based on Spearman correlation analysis, and this significant association was also demonstrated in subgroups. There was no evidence of publication bias. The combined OR was [3.27 (1.70, 6.30)] with no evidence of heterogeneity (<italic>I</italic><sup>2</sup> = 0%, <italic>p</italic> = 0.48) when sKlotho was treated as a categorical variable or [1.05 (1.01, 1.09)] with moderate heterogeneity (<italic>I</italic><sup>2</sup> = 63%, <italic>p</italic> = 0.10) when sKlotho was treated as a continuous variable based on multivariate logistic regression. No significant association was observed and the pooled OR was [0.29 (0.01, 11.15)] with high heterogeneity (<italic>I</italic><sup>2</sup> = 96%, <italic>p</italic> &lt; 0.001) according to multivariate linear regression analysis. There was an inverse association between sKlotho and parathyroid hormone levels. The combined coefficient (<italic>r</italic>) was [−0.20 (−0.40, −0.01)] with significant heterogeneity (<italic>I</italic><sup>2</sup> = 86%, <italic>p</italic> &lt; 0.001), and without obvious publication bias. No significant association was found between sKlotho and calcium or phosphate levels.</p><p><bold>Conclusion:</bold> There exists a significant association between decreased sKlotho level and increased risk of VC in CKD patients. This raises the possibility of applying sKlotho as a biomarker for VC in CKD populations. Large, prospective, well-designed studies or interventional clinical trials are required to validate our findings.</p>