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

Similar Datasets

Project description:BackgroundChronic kidney disease (CKD) is diagnosed in more than 26 million U.S. people, which increases the risk of many adverse events. α-Klotho was reported to have potential effects on kidney function. The purpose of this study was to investigated whether CKD prevalence is associated with α-Klotho levels in the U.S. people aged 40-79 years.MethodsThirteen thousand five hundred eighty-nine participates in the National Health and Nutrition Examination Survey 2007-2016 aged 40-79 with information of Klotho and kidney function were included. The association between CKD and Klotho was calculated using multivariate linear or logistic regression models with adjustment of several possibly confounding variables. Subgroup analyses stratified by age, BMI, and diabetes mellitus were conducted. The non-linear relationship between Klotho and dependent variables with a non-normality of residues was assessed using smooth curve fitting and the segmented regression (also known as piece-wise regression) models.ResultsAmong 13,589 participants, the median of Klotho levels was 803.10 pg/mL, mean eGFR of all participants was 86.96 (SD = 19.88) mL/min/1.73 m2, and CKD was diagnosed in 20.11% of them (N = 2733). In the fully adjusted model, eGFR was positively associated with Klotho (β = 5.14, 95%CI 4.13-6.15, p < 0.001), while CKD was negatively associated with Klotho (stage ≧ 1, OR = 0.62, 95% CI 0.50-0.76, p < 0.001; stage ≧ 3, OR = 0.31, 95% CI 0.24-0.41, p < 0.001). The non-linear relationship showed that occurrence of CKD stage> 1 and albuminuria were negatively associated with Klotho when Klotho smaller than turning point (for whether CKD stage> 1, turning point K = 6.85, Klotho < K, OR = 0.44, p < 0.001; for albuminuria, turning point K = 6.84, Klotho < K, OR = 0.59, p < 0.001).ConclusionSerum soluble Klotho levels were positively associated with eGFR and negatively associated with the prevalence of CKD, especially in elderly, obese, and diabetic patients.

Project description:Alpha-Klotho (alphaKl) regulates mineral metabolism such as calcium ion (Ca(2+)) and inorganic phosphate (Pi) in circulation. Defects in mice result in clinical features resembling disorders found in human aging. Although the importance of transmembrane-type alphaKl has been demonstrated, less is known regarding the physiological importance of soluble-type alphaKl (salphaKl) in circulation.The aims of this study were: (1) to establish a sandwich ELISA system enabling detection of circulating serum salphaKl, and (2) to determine reference values for salphaKl serum levels and relationship to indices of renal function, mineral metabolism, age and sex in healthy subjects.We successively developed an ELISA to measure serum salphaKl in healthy volunteers (n=142, males 66) of ages (61.1+/-18.5year). The levels (mean+/-SD) in these healthy control adults were as follows: total calcium (Ca; 9.46+/-0.41mg/dL), Pi (3.63+/-0.51mg/dL), blood urea nitrogen (BUN; 15.7+/-4.3mg/dL), creatinine (Cre; 0.69+/-0.14mg/dL), 1,25 dihydroxyvitamin D (1,25(OH)(2)D; 54.8+/-17.7pg/mL), intact parathyroid hormone (iPTH; 49.2+/-20.6pg/mL), calcitonin (26.0+/-12.3pg/mL) and intact fibroblast growth factor (FGF23; 43.8+/-17.6pg/mL). Serum levels of salphaKl ranged from 239 to 1266pg/mL (mean+/-SD; 562+/-146pg/mL) in normal adults. Although salphaKl levels were not modified by gender or indices of mineral metabolism, salphaKl levels were inversely related to Cre and age. However, salphaKl levels in normal children (n=39, males 23, mean+/-SD; 7.1+/-4.8years) were significantly higher (mean+/-SD; 952+/-282pg/mL) than those in adults (mean+/-SD; 562+/-146, P<0.001). A multivariate linear regression analysis including children and adults in this study demonstrated that salphaKl correlated negatively with age and Ca, and positively with Pi. Finally, we measured a serum salphaKl from a patient with severe tumoral calcinosis derived from a homozygous missense mutation of alpha-klotho gene. In this patient, salphaKl level was notably lower than those of age-matched controls.We established a detection system to measure human serum salphaKl for the first time. Age, Ca and Pi seem to influence serum salphaKl levels in a normal population. This detection system should be an excellent tool for investigating salphaKl functions in mineral metabolism.

Project description:BackgroundSoluble 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.MethodsUsing 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.ResultsThe 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.ConclusionsThe 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.