Liu QiFeng, Yu LiXia, Yin XiaoYa, Ye JianMing, Li ShaSha
Department of Nephrology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
Clinical Research & Lab Centre, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
Front Physiol. 2021 Aug 13;12:711904. doi: 10.3389/fphys.2021.711904. eCollection 2021.
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. Medical electronic databases were thoroughly searched for eligible publications on the association between sKlotho level and VC in CKD patients. Effectors, including correlation coefficients (), 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 -value. Origin of heterogeneity was explored by sensitivity analysis and subgroup analysis. 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 () was [-0.33 (-0.62, -0.04)] with significant heterogeneity ( = 89%, < 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 ( = 0%, = 0.48) when sKlotho was treated as a categorical variable or [1.05 (1.01, 1.09)] with moderate heterogeneity ( = 63%, = 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 ( = 96%, < 0.001) according to multivariate linear regression analysis. There was an inverse association between sKlotho and parathyroid hormone levels. The combined coefficient () was [-0.20 (-0.40, -0.01)] with significant heterogeneity ( = 86%, < 0.001), and without obvious publication bias. No significant association was found between sKlotho and calcium or phosphate levels. 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.
慢性肾脏病（CKD）患者中可溶性 Klotho（sKlotho）水平与血管钙化（VC）之间的相关性仍存在争议。我们旨在通过荟萃分析解决这一争议，并评估将 sKlotho 用作 VC 生物标志物的可行性。全面检索医学电子数据库，以查找有关 CKD 患者中 sKlotho 水平与 VC 之间关联的合格出版物。根据研究设计或效应量计算方法，提取并合并效应量，包括相关系数（）、比值比（OR）、风险比（HR）或β值以及 95%置信区间（CI）。根据 P 值，使用随机效应模型和固定效应模型生成合并效应量。通过敏感性分析和亚组分析探索异质性来源。共有 1199 篇出版物中的 10 项研究、1204 名参与者符合纳入标准并被纳入本荟萃分析。基于 Spearman 相关性分析，合并相关系数（）为[-0.33（-0.62，-0.04）]，具有显著异质性（I² = 89%，P < 0.001），且在亚组中也显示出这种显著关联。没有证据表明存在发表偏倚。当将 sKlotho 视为分类变量时，合并 OR 为[3.27（1.70，6.30）]，没有异质性证据（I² = 0%，P = 0.48）；当将 sKlotho 视为连续变量时，基于多变量逻辑回归，合并 OR 为[1.05（1.01，1.09）]，具有中度异质性（I² = 63%，P = 0.10）。根据多变量线性回归分析，未观察到显著关联，合并 OR 为[0.29（0.01，11.15）]，具有高度异质性（I² = 96%，P < 0.001）。sKlotho 与甲状旁腺激素水平之间存在负相关。合并系数（）为[-0.20（-0.40，-0.01）]，具有显著异质性（I² = 86%，P < 0.001），且无明显发表偏倚。未发现 sKlotho 与钙或磷水平之间存在显著关联。CKD 患者中 sKlotho 水平降低与 VC 风险增加之间存在显著关联。这增加了将 sKlotho 用作 CKD 人群中 VC 生物标志物的可能性。需要开展大型、前瞻性、设计良好的研究或干预性临床试验来验证我们的研究结果。
