Correlation Between Soluble Klotho and Vascular Calcification in Chronic Kidney Disease: A Meta-Analysis and Systematic Review
Qifeng Liu, Lixia Yu, Xiaoya Yin, JianMing Ye, Shasha Li
Abstract
Background: 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. Methods: Medical electronic databases were thoroughly searched for eligible publications on the association between sKlotho level and VC in CKD patients. Effectors, including correlation coefficients ( r ), 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 I 2 -value. Origin of heterogeneity was explored by sensitivity analysis and subgroup analysis. Results: 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 ( r ) was [−0.33 (−0.62, −0.04)] with significant heterogeneity ( I 2 = 89%, p < 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 ( I 2 = 0%, p = 0.48) when sKlotho was treated as a categorical variable or [1.05 (1.01, 1.09)] with moderate heterogeneity ( I 2 = 63%, p = 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 ( I 2 = 96%, p < 0.001) according to multivariate linear regression analysis. There was an inverse association between sKlotho and parathyroid hormone levels. The combined coefficient ( r ) was [−0.20 (−0.40, −0.01)] with significant heterogeneity ( I 2 = 86%, p < 0.001), and without obvious publication bias. No significant association was found between sKlotho and calcium or phosphate levels. Conclusion: 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.