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Elevated serum soluble alpha Klotho (s-αKlotho) levels are early biomarkers for overwork-related health risks, allowing timely intervention. This finding supports healthcare policies to limit work hours and promote a healthy work-life balance, reducing overwork-related diseases. Further research is needed for validation and intervention development. Objective: This study evaluates the utility of serum s-αKlotho levels as a quantifiable biomarker for overwork. Methods: Frontline medical workers aged 20–55 years from Yiling People's Hospital of Yichang were recruited. Criteria included nonsmokers, non-heavy drinkers, no chronic medication use, and no acute illnesses recently. Participants worked over 10 hours per day, 60 hours weekly, and had at least 3 years of experience. A control group was matched except for work conditions. Data were collected through surveys, and serum levels were measured. Results: Significant differences in serum Klotho were found between overwork and control groups. The overwork group had higher median s-αKlotho levels (49.99 pg/mL) compared to controls (27.88 pg/mL). Conclusion: Overworked medical workers exhibited elevated serum s-αKlotho, suggesting s-αKlotho as a potential biomarker for overwork. Future research should use multicenter designs with larger samples to validate findings. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) is a chronic microvascular complication caused by long-term hyperglycemia in patients with diabetes and an important cause of end-stage renal disease. Although some studies have shown that soluble Klotho(sKlotho) levels of patients with DN are lower than those without DN, in the early stage of patients with DN with normal renal function and albuminuria, the change in sKlotho is still controversial. Aim: This meta-analysis was conducted to statistically evaluate sKlotho levels in patients with DN. Methods: We searched the following electronic databases: Web of Science, Embase, PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI). The following search terms were used for the title or abstract: "diabetic kidney disease", "diabetic nephropathy", OR "DN" in combination with "Klotho". The meta-analysis results were presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Results: Fourteen articles were included in the meta-analysis. In our meta-analysis, we found that the sKlotho level in patients with DN was significantly lower than that in patients without DN (SMD: -1.52, 95% CI [-2.24, -0.80]), and it was also significantly lower in the early stage of DN (SMD: -1.65, 95% CI [-2.60, -0.70]). Conclusions: This systematic review was the first to evaluate the relationship between sKlotho levels and DN. The sKlotho level was significantly lower in the early stages of DN, indicating that sKlotho might be a new biomarker of DN in the future. [ABSTRACT FROM AUTHOR]

Objectives: Klotho (KL) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with KL genotypes. We aimed to explore the association of common genetic variants of KL with individual blood pressure (BP) responses to sodium and potassium through a dietary intervention study as well as long-term BP progression. Methods: We conducted family-based dietary interventions among 344 participants from 126 families in rural villages of northern China in 2004. Subjects sequentially underwent a baseline diet, a low-salt diet (51.3 mmol/day Na), a high-salt diet (307.8 mmol/day Na), and a high-salt + potassium supplementation diet (307.8 mmol/day Na + 60 mmol/day K). After dietary intervention, we followed up with these participants in 2009 and 2012. The associations between 6 single-nucleotide polymorphisms (SNPs) of KL and phenotypes were analyzed through a linear mixed-effects model. Results: SNPs rs211247 and rs1207568 were positively correlated with the BP response to high-salt diet in the dominant model after adjusting for confounders (β = 1.670 and 2.163, p = 0.032 and 0.005, respectively). BPs rs526906 and rs525014 were in a haplotype block. Block rs526906-rs525014 was positively correlated with diastolic BP response to potassium and potassium sensitivity in the additive model (β = 0.845, p = 0.032). In addition, regression analysis indicated that rs211247 was associated with long-term systolic BP alterations after 8 years of follow-up in the recessive model (β = 20.47, p = 0.032). Conclusions: Common variants of the KL gene might modify individual BP sensitivity to sodium or potassium and influence the long-term progression of BP, suggesting a potential role in the development of salt-sensitive hypertension. Thus, KL may be a new early intervention target for salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Background: Although Klotho-related research has seen a significant upsurge, the field lacks comprehensive analytical representation and in-depth exploration of pertinent areas such as prevailing research trends and key focus areas., Method: This review presents a bibliometric analysis of literature data gathered from the Web of Science Core Collection databases from January 1, 2000, to April 30, 2023. Parameters such as co-authorship, co-citation, co-occurrence, and the emergence of publications, countries, categories, references, and keywords were scrutinized predominantly using Citespace software., Results: Our investigation amassed a total of 3548 papers, with the United States leading in the quantity of publications (1175, accounting for 33.12%), followed by China (867, representing 24.44%), and Japan (439, accounting for 12.37%). While the United States is preeminent in the overall volume of publications, Scotland holds prominence in terms of centrality. Out of a total of 96 subject categories, urology and nephrology (573), and endocrinology and metabolism (542) were the two leading domains of Klotho-related publications. The 2011 paper titled "FGF23 induces left ventricular hypertrophy" by Faul C et al. holds the distinction of being the most frequently cited. The keywords "fibroblast growth factor 23," "phosphate homeostasis," and "functional variants" demonstrated the highest intensity, underscoring the potential of these research areas., Conclusion: As the volume of literature grows, the role of Klotho in disease management and its applicability as a marker in disease progression warrant vigilant tracking and study., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Klotho was involved in sodium reabsorption and the regulation of blood pressure. Animal studies indicated Klotho deficiency could mediate the development of salt-sensitive hypertension, indicating its correlation with salt sensitivity. We aimed to explore the responses of Klotho to salt intake through dietary intervention in Chinese adults. Forty-four participants were enrolled from Lantian county of Shaanxi, China. All participants sequentially underwent a 3-day normal diet, a 7-day low-Na + diet, and a 7-day high-Na + diet. The concentrations of serum Klotho were assessed by using ELISA kits. Serum level of Klotho was 360.44 ± 93.89 pg/mL at baseline and increased while changed to low-salt diet (478.65 ± 183.25 vs 360.44 ± 93.89 pg/mL, P < .001). During high-salt diet, serum Klotho decreased to 354.37 ± 98.16 pg/mL (P < .001, compared to low-salt diet). The overall responses of Klotho were more prominent in salt-resistant participants. Serum Klotho of salt-resistant group changed from 353.92 ± 97.65 pg/mL to 496.76 ± 196.21 pg/mL while changed from normal diet to low-salt diet (P < .001) and decreased to 350.37 ± 99.50 pg/mL during high-salt intake (P < .001). Furthermore, the response of serum Klotho to low-salt intervention was much greater in salt-resistant individuals than in salt-sensitive ones. The responses of serum Klotho to dietary salt intervention were influenced by salt sensitivity, which was more prominent in salt-resistant participants., (© 2020 Wiley Periodicals LLC.)

Background: Experimental studies indicate that Klotho deficiency is a pathogenic factor for CKD-related complications, including cardiovascular disease (CVD). However, the association between serum Klotho and clinical outcomes in nondiabetic CKD patients needs to be further clarified. We aimed to determine whether serum Klotho levels are associated with CVD events and mortality in predialysis CKD patients without diabetes., Methods: A total of 336 CKD stage 2-5 predialysis patients without diabetes were recruited and followed from the end of 2014 to January 2019 for CVD events and overall mortality. Serum Klotho was detected by ELISA and divided into quartiles (lowest, middle, second highest, and highest quartiles) according to their serum Klotho category., Results: After a median follow-up of 3.52 years (IQR 3.34-3.76), Kaplan-Meier analysis showed that, compared to participants with a Klotho level in the highest quartile (the reference category), those in the lowest Klotho quartile were associated with a higher all-cause mortality risk (HR = 7.05; 95% CI 1.59-31.25) and a higher CVD event risk (HR = 3.02; 95% CI 1.45-6.30). In addition, the middle Klotho quartile was also associated with CVD event risk (HR = 2.56; 95% CI 1.21-5.41). Moreover, in the multivariate-adjusted model, the lowest Klotho quartile remained significantly associated with all-cause mortality (HR = 5.17; 95% CI 1.07-24.96), and the middle Klotho quartile maintained a significant association with CVD event risk (HR = 2.32; 95% CI 1.03-5.21)., Conclusion: These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients., (© 2020 S. Karger AG, Basel.)

Background: Hemodialysis patients suffer from a serious threat of cerebrovascular disease. Klotho, as an aging-suppressor gene, contributes to protect on vascular calcification and oxidative stress, which are the risk factors of cerebrovascular disease. The purpose of the present study is to determine the relationship between serum klotho and cerebrovascular disease in patients receiving hemodialysis., Methods: Serum klotho levels of hemodialysis patients were measured by ELISA. Cerebrovascular diseases were diagnosed by CT or MRI scans. The cognitive function of hemodialysis patients with cerebrovascular disease were evaluated with a neuropsychological battery assessing domains of global cognition verbal memory, spatial memory, executive function and verbal fluency., Results: Eighty-eight patients were included, 57 ± 14 years, 63.64% male, 52.27% older than 60 years. Twenty-eight participants had cerebrovascular disease (23 cases had cerebral infarction, 5 cases had cerebral hemorrhage). The average level of serum klotho of all participants was 119.10 ± 47.29 pg/ml. The serum klotho level was significantly associated with cerebrovascular disease in hemodialysis patients (HR(95%CI) = 0.975(0.960-0.990), p = 0.001). The optimal cut-off value of serum klotho for predicting cerebrovascular disease in hemodialysis patients was 137.22 pg/ml, with a specificity of 96.4% and a sensitivity of 46.7%. But serum klotho was not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease (HR((95%CI) = 1.002(0.986-1.018), p = 0.776) or with cerebral infarction (HR(95%CI) = 1.005(0.987-1.023), p = 0.576)., Conclusions: The serum klotho level is a potential predictor of cerebrovascular disease in hemodialysis patients, but it is not an independent risk factor of cognitive impairment for hemodialysis patients with cerebrovascular disease.

Aims: Neuroinflammation contributed to the pathogenesis of multiple system atrophy (MSA). We aimed to detect the correlation between inflammatory mediators, such as Klotho (Klt), vitamin D (25(OH)D) and homocysteine (Hcy), and disease severity among MSA patients., Methods: A total of 53 MSA patients, 65 PD patients, and 62 normal subjects were recruited in our cross-sectional study. Serum Klotho (Klt), vitamin D (25(OH)D), and homocysteine (Hcy) levels were measured. Several scales were undertaken to assess the motor/nonmotor function and cognitive impairment of MSA., Results: Decreased Serum Klt and 25(OH)D levels and increased Hcy levels were found in patients with MSA, compared with healthy controls. These results were more pronounced in male patients. The three biomarkers also displayed differences between MSA and PD subgroups based on genders. Interestingly, Klt, 25(OH)D and Hcy levels associated with cognition impairment, motor dysfunction, mood/cardiovascular disorder among MSA patients. In addition, the combination of Klt, 25(OH)D and Hcy had a better diagnostic ability for distinguishing MSA patients from healthy subjects, as well as distinguishing male MSA patients from male PD patients., Conclusion: This study suggested that Klt, 25(OH)D and Hcy levels could be a potential predictor for MSA severity evaluation., (© 2017 John Wiley & Sons Ltd.)

Background/aims: The incidence of urolithiasis has considerably increased throughout the world in the last two decades. Clinical researches have showed an association between oxidative stress and stone formation. Emerging evidence indicated a novel function for klotho protein in anti-oxidative stress. In this study, we aimed at investigating a possible relationship between klotho gene polymorphisms and the risk of calcium oxalate urolithiasis in the population of Han nationality in Eastern China., Methods: Klotho gene polymorphisms rs3752472 in exon3, rs650439 in intron 4 and rs577912 in intron 1 were investigated in 426 patients with calcium oxalate stones compared with 282 age-matched healthy volunteers with no history of stone formation, using TaqMan SNP Genotyping Assays., Results: Significant differences were found between rs3752472 and the risk of nephrolithiasis as CC genotype of rs3752472 klotho polymorphism had almost 2-fold increased stone risk compared with the heterozygote genotype CT and homozygous genotype TT(95% CI=1.013-2.255, OR=1.512,p=0.043)., Conclusion: Our results showed that the rs3752472 polymorphism of klotho gene is associated with the risk of calcium oxalate urolithiasis and may act as a risk factor during stone formation in our study population., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Exposure to cadmium (Cd) can affect both DNA methylation and renal function, but there are few examples of the association between epigenetic markers and Cd-induced kidney damage. It has been suggested that hypermethylation of the genes RASAL1 and KLOTHO is associated with renal fibrogenesis. To investigate whether hypermethylation of RASAL1 and KLOTHO in peripheral blood DNA can be associated with Cd exposure and/or Cd-induced renal dysfunction, the degrees of methylation of RASAL1 and KLOTHO in peripheral blood DNA from 81 residents in Cd-polluted and non-polluted areas were measured using bisulfate-PCR-pyrosequencing. Changes in blood cadmium (BCd), urinary cadmium (UCd), and kidney parameters were measured, and the glomerular filtration rate (eGFR) was estimated. The levels of BCd and UCd correlated positively with the levels of DNA methylation in RASAL1 and in KLOTHO. The more heavily exposed residents (BCd, 4.23-13.22μg/L; UCd, 8.65-32.90μg/g creatinine) exhibited obvious renal dysfunction. Notably, when Cd concentration in blood and urine was adjusted, the increased methylation level in RASAL1 was inversely correlated with eGFR (P<0.01) but the relationship between hypermethylation of KLOTHO and eGFR was not statistically significant. The methylation of RASAL1 increased along with the increased abnormal prevalence of eGFR. Our findings suggest that Cd exposure can induce the hypermethylation of RASAL1 and KLOTHO. Hypermethylation of RASAL1 may be an indicator of the progress for chronic kidney disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)