Abstract
Objective Over decades, numerous inconsistent studies are reported on the relationship between soluble α-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 α-Klotho and renal function in patients with CKD. Materials and Methods 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 α-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. Results 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 αKlotho/FGF23 assays utilized, full length, or the C-terminal fragment of FGF23. The pooled r between α-Klotho and estimated glomerular filtration rate (eGFR), FGF-23 were 0.35 (95%CI, 0.23~0.46, 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 α-Klotho and eGFR stratified by research region, mean age, and eGFR, but heterogeneity exists in analyses of α-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. Conclusions There exists a significant positive correlation between soluble α-Klotho and eGFR in patients with CKD. Also, a significant negative correlation between α-Klotho and FGF23 levels is proven. This raises hope to employ αKlotho 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.
Highlights
The α-Klotho was originally identified as an aging suppressor by Kuro-M et al in 1977, the year when they found the Klotho-deficient mice displayed phenotypes resembling human premature-aging syndrome with shortened lifespan [1]
As an obligatory coreceptor of fibroblast growth factor 23(FGF23), it forms a complex with fibroblast growth factor receptor (FGFR) [6, 7], which can maintain mineral homeostasis by regulating urinary phosphorus reabsorption and inhibiting production of 1,25dihydroxy vitamin D in kidneys and suppressing synthesis and secretion of parathyroid hormone in parathyroid gland [8]
Contrary to what was mentioned above, some studies found that soluble α-Klotho levels had no significant correlation with estimated glomerular filtration rate (eGFR) [17,18,19] or even two studies reported α-Klotho were higher in patients with chronic kidney disease (CKD) [31, 36], we performed this review and meta-analysis to assess the correlation between soluble αKlotho levels and renal function in patients with CKD. In this meta-analysis, with a random effects model, we found a significant positive correlation between soluble αKlotho and eGFR in patients with CKD as the pooled Spearman correlation coefficient was 0.35 (95%confidence intervals (CIs), 0.23∼ 0.46)
Summary
Numerous inconsistent studies are reported on the relationship between soluble α-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 α-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 α-Klotho and renal function in patients with CKD. 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 αKlotho/FGF23 assays utilized, full length, or the C-terminal fragment of FGF23. There exists a significant positive correlation between soluble αKlotho and eGFR in patients with CKD. A significant negative correlation between α-Klotho and FGF23 levels is proven This raises hope to employ αKlotho and FGF23 as early biomarkers of CKD. 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
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