Dataset Information

Correlation between Soluble ?-Klotho and Renal Function in Patients with Chronic Kidney Disease: A Review and Meta-Analysis.

ABSTRACT:

Objective

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.

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 ?-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 ?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, 0.23~0.46, 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 ?-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.

Conclusions

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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC6109492 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Correlation between Soluble <i>α</i>-Klotho and Renal Function in Patients with Chronic Kidney Disease: A Review and Meta-Analysis.

Wang Qinglian Q Su Wenyan W Shen Zhenwei Z Wang Rong R

BioMed research international 20180812

<h4>Objective</h4>Over decades, numerous inconsistent studies are reported on the relationship between soluble <i>α</i>-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 <i>α</i>-Klotho and renal function in patients with CKD.<h4>Materials and methods</h4>We searched medical and scientific literature databases, PubMed and EMBASE (from the inception to October 2017), for publications t ...[more]

PMID: 30159331

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Project description:Background:Soluble Klotho has multiple systemic salutary effects. In animals, both acute and chronic kidney disease models display systemic Klotho deficiency. As such, there is considerable interest in investigating soluble Klotho as a biomarker in patients with different types and severity of kidney diseases. Unfortunately, there remains uncertainty regarding the best method to measure soluble Klotho in human serum samples. Methods:Using human serum samples obtained from several clinical cohorts with a wide range of kidney function, we measured soluble Klotho using a commercial enzyme-linked immunosorbent assay (ELISA) as well as with an immunoprecipitation-immunoblot (IP-IB) assay utilizing a synthetic antibody with high affinity and specificity for Klotho. Recovery of spiking with a known amount of exogenous Klotho was tested. A subset of samples was analyzed with and without the addition of a protease inhibitor cocktail at the time of collection or after the first freeze-thaw cycle to determine if these maneuvers influenced performance. Results:The IP-IB assay was superior to the ELISA at recovery of exogenous Klotho (81-115% versus 60-81%) across the spectrum of kidney function. Klotho measurements by IP-IB were highly correlated with estimated glomerular filtration rate (eGFR) (R?=?0.80, P?<?0.001) in comparison with the commercial ELISA, which exhibited minimal correlation with eGFR (R?=?0.18, P?=?0.12). Use of a protease inhibitor cocktail neither improved nor impaired performance of the IP-IB assay; however, subsequent freeze-thaw cycle resulted in a significant reduction in Klotho recovery and dissipated the correlation between Klotho levels and eGFR. With the ELISA, the use of protease inhibitor cocktail resulted in an increase in intrasubject variability. Conclusions:The IP-IB assay is preferable to the commercial ELISA to measure soluble Klotho concentrations in never-thawed serum samples of humans with varying severity of kidney disease. However, due to the labor-intensive nature of the IP-IB assay, further research is needed to secure an assay suitable for high-throughput work.