Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Qilu Pharmaceutical Co., Ltd., Jinan, China.
Biomed Res Int. 2018 Aug 12;2018:9481475. doi: 10.1155/2018/9481475. eCollection 2018.
Over decades, numerous inconsistent studies are reported on the relationship between soluble -Klotho and renal function in patients with chronic kidney disease (CKD). This study aims to perform a meta-analysis to figure out the correlations between soluble -Klotho and renal function in patients with CKD.
We searched medical and scientific literature databases, PubMed and EMBASE (from the inception to October 2017), for publications that reported studies on associations between soluble -Klotho and renal function in patients with CKD. Only publications in English were extracted. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Publication bias was tested, and sensitivity and subgroup analyses were performed to investigate potential heterogeneity.
Of 611 studies, 9 publications with 1457 patients were included into the analysis. The following data were extracted from the literature: first author, year of publication, research region, research index, sample size, average age and Pearson or Spearman correlation coefficient, study design, the Klotho/FGF23 assays utilized, full length, or the C-terminal fragment of FGF23. The pooled r between -Klotho and estimated glomerular filtration rate (eGFR), FGF-23 were 0.35 (95%CI, 0.230.46, and P<0.05), -0.10 (95%CI, -0.19-0.01, and P<0.05) with remarkable significance, indicating moderate heterogeneity. There was no significant heterogeneity between subgroups in analyses of -Klotho and eGFR stratified by research region, mean age, and eGFR, but heterogeneity exists in analyses of -Klotho and FGF-23 stratified by research region. There was no significant correlation between a-klotho and Ca and PTH and PHOS. There was no evidence of publication bias with Egger's test (p=0.360) or with Begg's test (p=0.902) and the distribution of funnel plots was symmetrical in all of our analysis.
There exists a significant positive correlation between soluble -Klotho and eGFR in patients with CKD. Also, a significant negative correlation between -Klotho and FGF23 levels is proven. This raises hope to employ Klotho and FGF23 as early biomarkers of CKD. However, further large prospective follow-up researches are needed to validate this hypothesis and to explore whether maintaining or elevating the Klotho level could improve renal function and complications in CKD patients.
数十年来，已有大量研究报道可溶性 Klotho 与慢性肾脏病（CKD）患者肾功能之间的关系并不一致。本研究旨在进行荟萃分析，以明确 CKD 患者可溶性 Klotho 与肾功能之间的相关性。
我们检索了医学和科学文献数据库 PubMed 和 EMBASE（从建库至 2017 年 10 月），以获取有关可溶性 Klotho 与 CKD 患者肾功能之间关系的研究报告。仅提取发表于英文期刊的文献。从每项研究中提取汇总相关系数（r）值，并计算 95%置信区间（CI）。对发表偏倚进行检验，并进行敏感性和亚组分析以探究潜在的异质性。
在 611 项研究中，有 9 项研究的 1457 例患者纳入分析。文献中提取的数据包括：第一作者、发表年份、研究区域、研究指标、样本量、平均年龄及 Pearson 或 Spearman 相关系数、研究设计、Klotho/FGF23 检测方法、全长或 FGF23 的 C 末端片段。可溶性 Klotho 与估算肾小球滤过率（eGFR）、FGF-23 的汇总 r 值分别为 0.35（95%CI，0.230.46，P<0.05）和-0.10（95%CI，-0.19-0.01，P<0.05），差异均有统计学意义，提示存在中度异质性。但按研究区域、平均年龄和 eGFR 对可溶性 Klotho 与 eGFR 进行分层分析时，组间无明显异质性，但按研究区域对可溶性 Klotho 与 FGF-23 进行分层分析时，异质性明显。可溶性 Klotho 与 Ca、PTH 和 PHOS 之间无明显相关性。Egger 检验（p=0.360）或 Begg 检验（p=0.902）均未发现发表偏倚的证据，且我们所有分析的漏斗图分布均对称。
CKD 患者中可溶性 Klotho 与 eGFR 之间存在显著正相关，同时 Klotho 与 FGF23 水平之间存在显著负相关。这提示 Klotho 和 FGF23 有望成为 CKD 的早期生物标志物。然而，还需要进一步开展大型前瞻性随访研究以验证该假说，并探究维持或提高 Klotho 水平是否可改善 CKD 患者的肾功能和并发症。
