Klotho Concentrations Research Articles

Association between Serum Klotho Concentration and Heart Failure in Adults, NHANES 2007-2016

Association between Serum Klotho Concentration and Heart Failure in Adults, NHANES 2007-2016

Association Between the Anti-Aging Protein Klotho and Sleep Duration in General Population.

PurposeSleep duration is associated with aging. However, the relationship between sleep duration and the concentration of the protein klotho in the serum remains unknown in the general population of the United States. Hence, this study aimed at exploring the association between them.MethodsParticipants whose data included klotho protein and sleep duration variables in the National Health and Nutrition Examination Survey data from 2007 to 2016 were utilized for this analysis.ResultsSleep duration was non-linearly associated with the level of klotho protein in the serum, with a negative association between sleep duration and serum klotho concentration after adjusting for confounding variables (β = −7.6; 95% CI: −11.3, −4.0; P < 0.001). The conversion of the sleep duration from a continuous variable to a categorical variable (tertile: T1: <5.5 hours; T2: 5.5–7.5 hours; T3: >7.5 hours) revealed that the serum klotho of the participants in the highest tertile (>7.5 hours) was 21.9 pg/mL lower (95% CI: −38.6, −5.2; P = 0.01) than those in the lowest tertile (<5.5 hours).ConclusionOur results revealed that people who sleep more than 7.5 hours per night have decreased levels of the anti-aging protein klotho in their serum, thus being more at risk of aging-related syndromes.

Patients with Earlobe Crease May Associate with Lower Concentration of the Age-Suppressing Hormone Klotho

ObjectiveEarlobe crease (ELC) has been considered as a skin sign of atherosclerosis, and its pathophysiological mechanism is still unclear. Our study aims to test the hypothesis that ELC patients with lower serum levels of the age-suppressing hormone Klotho, which is not only associated with premature aging but also with endothelial dysfunction, may be associated with atherosclerosis.MethodsA total of 135 patients aged 40–68 years underwent coronary angiography. According to the presence or absence of coronary heart disease (CAD) and ELC, they were divided into three groups: CAD group and ELC group (ELC group, n = 45); no ELC group (non-ELC group, n = 45). There was no ELC or CAD in the control group (control group, n = 45). Serum Klotho concentration was obtained by enzyme-linked immunosorbent assay (ELISA).ResultsThe Klotho level in the ELC group was 365.6 ± 38.1 pg/mL, while the Klotho level in the non-ELC group was 568.8 ± 44.9 pg/mL. It is worth noting that the Klotho level of the ELC group was significantly lower than that of the non-ELC group (P < 0.001). The serum Klotho level of the control group was higher than that of the non-ELC group (593.3±45.3 vs 568.8±44.9 pg/mL, P = 0.702), but the difference was not statistically significant. Multiple logistic regression analysis showed that the Klotho level is a parameter that affects the appearance of ELC.ConclusionSerum Klotho levels were considerably lower in patients with ELC. We concluded that the perturbations of Klotho in patients might be associated with ELC and with CAD.

Impact of a single bout of resistance exercise on serum Klotho in healthy young men.

BackgroundIt has been shown that Klotho protects vascular endothelial function. Given that a single bout of resistance‐exercise‐induced hypertensive stimulus causes endothelial dysfunction, we postulated that acute resistance exercise would reduce serum Klotho levels. In this respect, the reduction in serum Klotho levels would be associated with the response of flow‐mediated dilation (FMD). Therefore, the purpose of this study was to investigate the impact of acute resistance exercise on the Klotho response in serum. In addition, we examined the relationship between the serum Klotho and FMD responses following acute resistance exercise.MethodsTwelve untrained men participated in this study (20.4 ± 0.3 years). Following baseline measurements (blood pressure, blood collection, FMD), subjects performed leg extensions, which consisted of 10 repetitions for five sets at 70% of one‐repetition maximum. After the exercise, measurement of blood pressure, blood collection, and FMD assessment were repeated for 60 min. We analyzed Klotho and endothelin‐1 (ET‐1) concentrations in blood serum.ResultsAs expected, the exercise significantly elevated blood pressure and led to decreased FMD (p < 0.05). However, Klotho concentrations were significantly increased following exercise (p < 0.05). No correlation was observed in Klotho and FMD responses following acute resistance exercise. However, there was a significant positive correlation between Klotho and ET‐1 in response to resistance exercise (p < 0.05).ConclusionIn conclusion, the present study reveals that serum Klotho significantly increased following a single bout of resistance exercise. However, the increase in Klotho may not associate with the acute reduction in endothelial function.

Low Serum Klotho Associated With All-cause Mortality Among a Nationally Representative Sample of American Adults.

α-Klotho (klotho) is a protein involved in suppressing oxidative stress and inflammation. In animal models, it is reported to underlie numerous aging phenotypes and longevity. Among a nationally representative sample of adults aged 40-79 years in the United States, we investigated whether circulating concentrations of klotho is a marker of mortality risk. Serum klotho was measured by ELISA on 10 069 individuals enrolled in the National Health and Nutrition Examination Survey between 2007 and 2014. Mortality follow-up data based on the National Death Index were available through December 31, 2015. After a mean follow-up of 58 months (range: 1-108), 616 incident deaths occurred. Using survey-weighted Cox regression models adjusted for age, sex, and survey cycle, low serum klotho concentration (<666 pg/mL) was associated with a 31% higher risk of death (compared to klotho concentration > 985 pg/mL, hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.00, 1.71, p = .05). Associations were consistent for mortality caused by heart disease or cancer. Associations of klotho with all-cause mortality did not appear to differ by most participant characteristics. However, we observed effect modification by physical activity, such that low levels of serum klotho were more strongly associated with mortality among individuals who did not meet recommendation-based physical activity guidelines. Our findings suggest that, among the general population of American adults, circulating levels of klotho may serve as a marker of mortality risk.

Soluble Klotho and Incident Hypertension.

Hypertension is associated with significant morbidity and mortality despite effective antihypertensive therapies. Soluble klotho is a circulating protein that in preclinical studies is protective against the development of hypertension. There are limited studies of klotho and blood pressure in humans. Within the Health, Aging, and Body Composition Study, a cohort of well-functioning older adults, soluble klotho was measured in serum. We evaluated the cross-sectional and longitudinal association between klotho and blood pressure, prevalent hypertension, incident hypertension, and BP trajectories. Analyses were adjusted for demographics, cardiovascular disease and kidney disease risk factors, and measures of mineral metabolism including calcium, phosphate, parathyroid hormone, 25(OH) vitamin D, and fibroblast growth factor 23. The median klotho concentration was 630 pg/ml (478-816, 25th to 75th percentile). Within the cohort, 2093 (76%) of 2774 participants had prevalent hypertension and 476 (70%) of the remaining 681 developed incident hypertension. There was no association between klotho and prevalent hypertension or baseline systolic BP, but higher klotho was associated with higher baseline diastolic BP (fully adjusted β=0.92 mmHg, 95% confidence interval, 0.24 to 1.60 mmHg, higher per two-fold higher klotho). Higher baseline serum klotho levels were significantly associated with a lower rate of incident hypertension (fully adjusted hazard ratio, 0.80; 95% confidence interval, 0.69 to 0.93 for every two-fold higher klotho). Higher klotho was also associated with lower subsequent systolic BP and diastolic BP (-0.16, 95% confidence interval, -0.31 to -0.01, mmHg lower systolic BP per year and -0.10, 95% confidence interval, -0.18 to -0.02, mmHg lower diastolic BP per year, for each two-fold higher klotho). Higher klotho is associated with higher baseline diastolic but not systolic BP, a lower risk of incident hypertension, and lower BP trajectories during follow-up.

Nephroprotective effect of dapagliflozin in type 2 diabetes mellitus: A potential role of Klotho protein

Abstract. The present study aimed to investigate the dynamics of clinical and laboratory parameters and serum Klotho protein level in patients with diabetic kidney disease using nephroprotective therapy combined with an inhibitor of the sodium-glucose cotransporter 2 (SGLT2) dapagliflozin.&#x0D; Methods. A total of 76 type 2 diabetic patients with diabetic nephropathy (DN) were examined in this prospective study. Control group - 20 healthy subjects. 53 patients received a standard course of treatment, which included metformin, renin-angiotensin-aldosterone system blockers and statins. In addition to standard therapy, 23 patients have been prescribed the SGLT2 inhibitor dapagliflozin 10 mg per day. The treatment follow-up period was six months. Klotho concentration was determined by an enzyme-linked immunosorbent assay.&#x0D; Results. The development of DN in type 2 diabetic patients was accompanied by a significant decrease in soluble Klotho protein in comparison with controls and patients without nephropathy. During follow-up, Klotho protein level was changed significantly in the group of DN patients with albuminuria. Standard therapy resulted in Klotho concentration increase by 14% compared to pre-treatment values; a more demonstrative increase in the Klotho level was found in the dapagliflozin group (almost 23%).&#x0D; Conclusions. SGLT2 inhibitor treatment resulted in a significant increase of pleiotropic serum protein Klotho in patients with type 2 diabetes and diabetic kidney disease.

Low serum klotho concentration is associated with worse cognition, psychological components of frailty, dependence, and falls in nursing home residents

Serum alpha-klotho (s-klotho) protein has been linked with lifespan, and low concentrations of s-klotho have been associated with worse physical and cognitive outcomes. Although its significance in aging remains unclear, s-klotho has been proposed as a molecular biomarker of frailty and dependence. This study is a secondary analysis of data from a clinical trial performed in a population of 103 older individuals living in 10 nursing homes in Gipuzkoa (Spain). We aimed to elucidate associations between s-klotho (as measured by enzyme-linked immunosorbent assay) and body composition, physical fitness, and cognition, as well as frailty and dependence (determined using validated tests and scales). In addition, we investigated the association of s-klotho concentration with falls in the six months following the initial assessment. Low s-klotho levels were associated with a lower score in the psychological component of the Tilburg Frailty Indicator, a worse score in the Coding Wechsler Adult Intelligence Scale, and a greater dependence in activities of daily living. Moreover, participants with lower s-klotho concentrations suffered more falls during the 6 months after the assessment. Future translational research should aim to validate klotho’s putative role as a biomarker that could identify the risk of aging-related adverse events in clinical practice.

Evaluation of the bone tissue metabolism in patients with generalized periodontitis of various degrees exposed to work-related harmful factors by the oral fluid Klotho protein content

The aim of the work is to study the Klotho protein concentration in the oral fluid of patients exposed to work-related harmful factors and to reveal correlations with the content of bone tissue and vitamin D metabolism markers. Materials and methods. The study group consisted of 126 patients with generalized periodontitis of initial (n = 8), I (n = 32), II (n = 68) and III (n = 18) degree of severity, chronic course, working in hazardous conditions of the “Dniprospetsstal” plant in Zaporizhzhia. The comparison group consisted of 32 periodontitis patients of initial (n = 5), I (n = 10), II (n = 11) and III (n = 6) degree of severity without exposure to work-related harmful factors. The control group included 20 otherwise healthy individuals aged 19–25 years without signs of periodontal diseases. The levels of vitamin D, VDBP, MMP-8 and osteocalcin were determined by enzyme-linked immunosorbent assays, the concentration of soluble Klotho was detected by the enzyme-linked ImmunoChem-2100 immunosorbent assay. Results. It was found, that in the study group of patients working in hazardous work-related conditions, the decrease in oral fluid Klotho protein concentration was greater, than in the comparison group of patients with periodontal diseases, but not exposed to work-related hazardous conditions. The indicator of Klotho protein is an early marker of the periodontal disease progression and varies inversely with the severity of periodontitis, starting in the early stages of the disease. The correlation coefficient between the level of Klotho protein and the degree of the disease severity in the comparison group patients was γ = -0.957, P &lt; 0.05 and γ = -0.906, P &lt; 0.05 – in the study group. In the patients with periodontal diseases, there was a decrease in the Klotho protein concentration with a parallel increase in the marker of bone tissue destruction - MMP-8, and a decrease in the marker of remodeling – osteocalcin, as compared to the controls. The decrease in Klotho protein concentration occurred with vitamin D deficiency and worsened with the vitamin D-binding protein reduction. Conclusions. The Klotho protein is the early, sensitive and specific diagnostic biomarker in dental diseases, and its measurement can be used as a predictor of inflammatory periodontal disease and its complications. The Klotho protein is one of the main regulators of bone metabolic processes.

Klotho, FOXO1 and cytokines associations in patients with coronary artery disease

IntroductionAtherosclerosis is one of the main reasons for adult mortality in advanced populations and countries with high stress levels. Klotho family are single-pass trans-membrane proteins that involve in the genesis and progression of various diseases, including acardiovascular disease, apoptosis and stress oxidative imbalance.Present study, investigates the pattern of changes in Klotho and FOXO1 gene expressions and levels in atherosclerosis. MethodsPresent case control study consisted of 79 patients with atherosclerosis and 78 healthy controls. PBMC (peripheral mono-nuclear blood cells) expression levels of Klotho and FOXO1 were assayed, using qPCR method. Serum concentration of Klotho and FOXO1 were measured by ELISA method. ResultsA significant reduction was found in PBMC genes expression levels of Klotho (P < 0.01) of patients as comparison with controls. PBMC Gene expression of FOXO1 in patients was increased significantly (P < 0.01) when compared with controls. Pearson analysis showed a positive correlation between PBMC Klotho gene expression and Klotho levels of patients (P < 0.01). The correlation between serum concentrations of Klotho and FOXO1 of patients was also positive significantly (P < 0.01). AUC of ROC for gene expression and serum concentration of Klotho in patients were 0.701 and 0.737 respectively. ConclusionInvestigating the PBMC gene expression and serum concentration of Klotho in patients with atherosclerosis is suggested could be a convenient novel biomarker for predicting, prognosis, monitoring the disease progression and designing a suitable drug for patients with atherosclerosis.

No significant association of serum klotho concentration with blood pressure and pulse wave velocity in a Chinese population

Klotho, an important anti-aging protein, may be related to elevated blood pressure (BP) and arterial stiffness. We aimed to investigate associations between the serum klotho concentration and peripheral/central BP and arterial stiffness based on the carotid–femoral pulse wave velocity (cfPWV) in a Chinese population. We invited all inhabitants aged ≥ 18 years in two Dali communities for participation. The SphygmoCor system was used to record radial arterial waveforms. Aortic waveforms were derived using a generalized transfer function. The central BP was assessed by calibrating the brachial BP, which was measured using an oscillometric device. The serum klotho concentration was measured using an enzyme-linked immunosorbent assay and logarithmically transformed. Of the 716 participants (mean age: 51.9 ± 12.6 years), 467 (65.2%) were women. The median serum klotho concentration was 381.8 pg/mL. The serum klotho concentration did not significantly differ between patients with and without hypertension (P > 0.05) and between those with and without arterial stiffness (cfPWV ≥ 10 m/s) (P > 0.05). After adjusting for confounders, the serum klotho concentration was not significantly associated with the peripheral or central BP (P > 0.05) and cfPWV (P > 0.05). Our data indicated that the serum klotho concentration was not associated with BP or cfPWV in the general Chinese population.

Exercise intensity regulates cytokine and klotho responses in men

BackgroundShort-term exercise training programs that consist of moderate intensity endurance training or high intensity interval training have become popular choices for healthy lifestyle modifications, with as little as two weeks of training being shown to improve cardiorespiratory fitness and whole-body glucose metabolism. An emerging concept in exercise biology is that exercise stimulates the release of cytokines and other factors into the blood that contribute to the beneficial effects of exercise on metabolism, but whether these factors behave similarly in response to moderate and high intensity short term training is not known. Here, we determined the effects of two short-term exercise training programs on the concentrations of select secreted cytokines and Klotho, a protein involved in anti-aging.MethodsHealthy, sedentary men (n = 22) were randomized to moderate intensity training (MIT) or sprint intensity training (SIT) treatment groups. SIT consisted of 6 sessions over 2 weeks of 6 × 30 s all out cycle ergometer sprints with 4 min of recovery between sprints. MIT consisted of 6 sessions over 2 weeks of cycle ergometer exercise at 60% VO2peak, gradually increasing in duration from 40 to 60 min. Blood was taken before the intervention and 48 h after the last training session, and glucose uptake was measured using [18F]FDG‐PET/CT scanning. Cytokines were measured by multiplex and Klotho concentrations by ELISA.ResultsBoth training protocols similarly increased VO2peak and decreased fat percentage and visceral fat (P < 0.05). MIT and SIT training programs both reduced the concentrations of IL-6, Hepatocyte Growth Factor (HGF) and Leptin. Interestingly, MIT, but not SIT increased monocyte chemoattractant protein-1 (MCP-1) concentrations, an exercise-induced cytokine, as well as Klotho concentrations.ConclusionShort-term exercise training at markedly different intensities similarly improves cardiovascular fitness but results in intensity-specific changes in cytokine responses to exercise.

Exercise-Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression.

Irisin, which can be released in the hippocampus after physical exercise, is demonstrated to have beneficial effects on neurovascular diseases. This study investigated the impact of exercise linked-irisin on mortality and cognition in a mice model of cerebral ischemia and further explored its underlying mechanism. The cerebrospinal concentrations of irisin and klotho from ischemic stroke patients were measured with an enzyme-linked immunosorbent assay (ELISA). The cognitive function of mice was evaluated by a series of behavioural experiments. The expressions of klotho, MnSOD, and FOXO3a in the hippocampus of mice were detected by Western blot. Superoxide production in the brain tissue of mice was evaluated with the dihydroethidium (DHE) dying. The results demonstrated that stroke patients showed a positive correlation between their CSF irisin concentration and klotho concentration. In addition, when mice subjected to cerebral ischemia, their cognitive function was impaired, the protein expressions of klotho, MnSOD, and FOXO3a downregulated, and the production of reactive oxygen species (ROS) increased compared with the sham group. After pretreatment with exogenous irisin, improved cognitive impairment, upregulated protein expressions of klotho, MnSOD, and FOXO3a, and reduced ROS generation were observed in mice with MCAO. However, the neuroprotective effects of irisin compromised with the evidence of severe cognitive impairment, decreased protein expressions of MnSOD and FOXO3a, and increased ROS production in klotho knockout mice. Thus, our results indicated that exercise-linked irisin could prevent mortality and improve cognitive impairment after cerebral ischemia by regulating klotho expression.

Determining the optimal cholecalciferol dosing regimen in children with CKD: a randomized controlled trial.

The optimal treatment regimen for correcting 25-hydroxyvitamin D (25OHD) deficiency in children with chronic kidney disease (CKD) is not known. We compared cholecalciferol dosing regimens for achieving and maintaining 25OHD concentrations ≥30 ng/mL in children with CKD stages 2-4. An open-label, multicentre randomized controlled trial randomized children with 25OHD concentrations <30 ng/mL in 1:1:1 to oral cholecalciferol 3000 IU daily, 25 000 IU weekly or 100 000 IU monthly for 3 months (maximum three intensive courses). In those with 25OHD ≥30 ng/mL, 1000 IU cholecalciferol daily (maintenance course) was given for up to 9 months. Primary outcome was achieving 25OHD ≥30 ng/mL at the end of intensive phase treatment. Ninety children were randomized to daily (n = 30), weekly (n = 29) or monthly (n = 31) treatment groups. At the end of intensive phase, 70/90 (77.8%) achieved 25OHD ≥30 ng/mL; 25OHD concentrations were comparable between groups (median 44.3, 39.4 and 39.3 ng/mL for daily, weekly and monthly groups, respectively; P = 0.24) with no difference between groups for time to achieve 25OHD ≥30 ng/mL (P = 0.28). There was no change in calcium, phosphorus and parathyroid hormone, but fibroblast growth factor 23 (P = 0.002) and klotho (P = 0.001) concentrations significantly increased and were comparable in all treatment groups. Irrespective of dosing regimen, children with glomerular disease had 25OHD concentrations lower than non-glomerular disease (25.8 versus 41.8 ng/mL; P = 0.007). One child had a 25OHD concentration of 134 ng/mL, and 5.5% had hypercalcemia without symptoms of toxicity. Intensive treatment with oral cholecalciferol as daily, weekly or monthly regimens achieved similar 25OHD concentrations between treatment groups, without toxicity. Children with glomerular disease required higher doses of cholecalciferol compared with those with non-glomerular disease.

Decreased concentration of klotho and increased concentration of FGF23 in the cerebrospinal fluid of patients with narcolepsy

Objectiveto explore the status of concentration of klotho and fibroblast growth factor 23 (FGF23) in cerebrospinal fluid (CSF) of patients with narcolepsy. Patients/methods59 patients with narcolepsy and 17 control individuals were enrolled. We used radioimmunoassay, human klotho enzyme-linked immunosorbent assay (ELISA), human intact FGF23 ELISA and spectrophotometry to measure hypocretin-1, klotho, FGF-23 and phosphorus, respectively. T-Student Test was used to compare klotho and phosphate concentrations, Mann–Whitney U Test were used to compare FGF-23 levels between groups. ANOVA Test was used to compare klotho and phosphate CSF concentrations among narcolepsy patients with CSF hypocretin-1 <110 pg/ml (HCRT-) and narcolepsy patients with CSF hypocretin-1 >110 pg/ml (HCRT+) versus control subjects. ResultsKlotho and phosphorus CSF levels were lower in narcoleptic patients than in control (908.18 ± 405.51 versus 1265.78 ± 523.26 pg/ml; p = 0.004 and 1.34 ± 0.25 versus 1.58 ± 0.23 mg/dl; p = 0.001, respectively). We found higher FGF-23 levels in narcoleptic patients (5.51 versus 4.00 pg/mL; p = 0.001). Klotho and phosphorus CSF levels were lower in both HCRT- and HCRT+ than controls. Moreover, there were higher FGF-23 levels in both HCRT-/HCRT+ groups versus controls. However, we did not find differences comparing HCRT- and HCRT+ groups, analyzing CSF klotho, FGF-23 or phosphorus levels. ConclusionsPatients with narcolepsy have decreased CSF concentration of klotho and increased CSF levels of FGF-23. These findings may play a role in understanding the pathogenesis of narcolepsy.

Effects of salt intervention on serum levels of Klotho influenced by salt sensitivity.

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±93.89pg/mL at baseline and increased while changed to low-salt diet (478.65±183.25 vs 360.44±93.89pg/mL, P<.001). During high-salt diet, serum Klotho decreased to 354.37±98.16pg/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±97.65pg/mL to 496.76±196.21pg/mL while changed from normal diet to low-salt diet (P<.001) and decreased to 350.37±99.50pg/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.

Investigation on urinary and serum alpha klotho in dogs with chronic kidney disease

BackgroundAs a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phosphate metabolism. The kidney is known to be the main source of soluble alpha-klotho and the principal regulator of its concentration. Previous studies in human participants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD.ResultsSerum and urinary alpha klotho concentrations were measured by a commercially available canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal–Wallis test. Spearman’s correlation coefficient was used to evaluate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations. The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD was significantly lower than those in the control group. There was no significant correlation between serum alpha-klotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and serum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure.ConclusionsUrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho is associated with CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Although serum klotho concentration was negatively correlated with sSDMA levels, it was not apparently related to IRIS CKD stage or other parameters known to be associated with CKD.

Circulating Klotho Response To A Behavioral Weight Loss Intervention In Adults With Overweight Or Obesity

Klotho, a biomarker of aging, is associated with a slower aging process. Klotho concentration is lower among adults with obesity compared to normal-weight adults, and exercise may independently increase levels of Klotho. Whether Klotho is altered by weight loss and whether there is an added effect of exercise are not understood. PURPOSE: This study examined changes in Klotho concentration in response to a behavioral weight loss intervention among adults with overweight or obesity. METHODS: A subset of 152 adults (age: 45.4+8.0 years; BMI: 32.1+3.7 kg/m2) who participated in a 12-month weight loss intervention were classified as an intervention “responder” (achieved >10% weight loss at both 6- and 12 months) or “non-responder” (achieved <5% weight loss at both 6- and 12 months). Intervention conditions included: 1) diet only (1200-1800 kcal/day), 2) diet plus 150 min/wk of moderate-to-vigorous intensity physical activity (MVPA) per week, 3) or diet plus 250 min/wk of unsupervised MVPA per week. Measures of height, weight, body composition, cardiorespiratory fitness, and Klotho were completed at baseline, 6-, and 12 months. Klotho was analyzed using solid-phase sandwich ELISA kits. RESULTS: There were significant (p<0.0001) changes in weight (-12.5±9.1 kg), percent body fat (-7.1±5.5%), lean body mass (-1.7±2.0 kg), and cardiorespiratory fitness (+3.3±4.1 ml/kg/min) from baseline to 12-months. Klotho significantly (p=0.009) changed across the 12 months (baseline: 933±381 pg/mL; 6 months: 985±450 pg/mL; 12 months: 940±423 pg/mL), with no difference by intervention group or weight loss response. Participants who performed physical activity had non-significantly greater changes in Klotho. Klotho was consistently associated with lean body mass at baseline (r=-0.19), 6 (r=-0.23), and 12 months (r=-0.19) (p<0.05). Klotho was not predictive of change in weight, body composition, or fitness. CONCLUSION: Klotho significantly, but modestly, increases with weight loss; however, the increase in Klotho was not sustained throughout the intervention. There may be an influence of physical activity on change in Klotho with weight loss, but this warrants further investigation. Further investigation to examine how weight loss and physical activity may alter biomarkers of aging in adults with obesity may be warranted.

Serum Klotho protein level in type 2 diabetic patients depending on the renal function

The study aimed to assess serum Klotho protein level in type 2 diabetic patients depending on kidney function.&#x0D; Methods. This observational study included 72 patients with diabetes mellitus (DM) and 26 patients with acute coronary syndrome. The control group consisted of 20 healthy subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR), the diabetics were divided into the following groups: group I included the patients with normal GFR and without albuminuria (n = 25); group ІІ consisted the patients with normal GFR and albuminuria (n = 23); group III – the patients with reduced GFR and albuminuria (n = 24) and group ІV included the patients with acute coronary syndrome (n = 26).&#x0D; The GFR was calculated using the CKD EPI formula (KDIGO 2012). The concentration of Klotho protein was determined by enzyme-linked immunosorbent assay.&#x0D; Results. The development of diabetic nephropathy in type 2 diabetic patients accompanied by a significant decrease of soluble Klotho compared with the controls and the patients of the1-st group. The level of Klotho protein in the group of patients with albuminuria decreased to (490.66 ± 58.76) pg/ml (p &lt;0.05). The lowest concentration of Klotho (443.58 ± 46.92) pg/ml was found in the advanced stages of diabetic nephropathy, namely in patients with albuminuria and impaired renal function. Moreover, a significantly decreased serum Klotho was observed in acute coronary syndrome group in comparison with the control group (p &lt;0.05). There were inverse correlations of Klotho concentration with urinary albumin and blood creatinine levels and a direct correlation between Klotho and GFR.&#x0D; Conclusions. The obtained data indicated the key role of Klotho protein in the formation of renal pathology in type 2 diabetes and the feasibility of practical use of Klotho determination as an early diagnostic marker of renal disorders and cardiovascular risk assessment. The strategies improving Klotho production may be useful in the reduction of both renal and vascular lesions progression in type 2 diabetic patients.

Klotho and fibroblast growth factors 19 and 21 serum concentrations in children and adolescents with normal body weight and obesity and their associations with metabolic parameters

BackgroundFibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components.MethodsThis was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components.ResultsThe study was conducted with 174 children/adolescents aged 6–17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score.ConclusionsKlotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.