Serum α-Klotho Research Articles

Serum α-Klotho associated with oral health among a nationally representative sample of US adults.

BackgroundLow klotho is associated with aging-related traits. However, no study has assessed the association between klotho and oral health in a large sample of population. This study aimed to explore the association between serum α-klotho and oral health in US Adults.MethodsData were from the National Health and Nutrition Examination Survey. Oral health parameters included periodontitis, self-rated oral health, and tooth loss. Logistic regression and restricted cubic spline models were adopted to evaluate the associations.ResultsA total of 6187 participants were included in the study. The median of the α-klotho level was 815.2 pg/mL. Serum α-Klotho was significantly lower in participants with poor oral health (all P <0.01). Compared with the highest tertile, the lowest tertile of α-klotho was associated with moderate/severe periodontitis, poor-rated oral health, and tooth loss, with OR (95% CI) being 1.21 (1.01, 1.48), 1.26 (1.01, 1.56) and 1.38 (1.05, 1.84), respectively. An increment of per 1 standard deviation in the α-klotho concentration was associated with lower odds of moderate/severe periodontitis (OR: 0.93; 95% CI: 0.87, 0.99). Linear dose-response relationships were found between α-klotho and the odds of moderate/severe periodontitis (P for non-linearity=0.88) and poor-rated oral health (P for non-linearity=0.66). An L-shaped dose-response relationship was found between levels of α-klotho and the odds of tooth loss (P for non-linearity=0.04).ConclusionsSerum α-klotho was associated with oral health. Further studies are necessary to clarify the potential mechanisms and demonstrate the predictive ability of klotho in oral diseases.

Para-dichlorobenzene exposure and serum α-Klotho levels among US participants in their middle and late adulthood

Para-dichlorobenzene exposure and serum α-Klotho levels among US participants in their middle and late adulthood

Association between environmental exposure to perchlorate, nitrate, and thiocyanate and serum α-Klotho levels among adults from the National Health and nutrition examination survey (2007–2014)

Background & aimsAging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels.MethodsThis secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007–2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels.ResultsUrinary thiocyanate levels were negatively associated with α-Klotho levels (β = − 0.006; 95% confidence interval, − 0.010 to − 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (β = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels.ConclusionsUrinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases.

Association of α-klotho and lead and cadmium: A cross-sectional study

Epigenetic aging is associated with harmful health effects such as oxidative stress from heavy metal exposure. We considered the relationship between genes and heavy metals in association with oxidative stress and then investigated the association between serum α- klotho and lead and cadmium exposure among adults in the United States from 2007 to 2016 participating in the National Health and Nutrition Examination Survey (NHANES). Samples included 9800 adults aged 40 to 79 years with measurements of serum α-klotho, lead and cadmium, and complete covariate data. Lead and cadmium levels were measured by inductively coupled plasma mass spectrometry and serum α-klotho levels were measured using enzyme-linked immunosorbent assay (ELISA). Multivariate linear regression analysis was used to estimate the association between serum α-klotho and blood lead, blood cadmium, and urinary cadmium. A percent increase in blood lead, blood cadmium, and urinary cadmium was associated with a statistically significant 4.0 % (p < 0.001), 2.0 %, (p = 0.003) and 1.0 % (p = 0.020) decrease in serum klotho. After adjustment, a percent increase in blood lead was associated with a statistically significant 4.0 % (p < 0.001) decrease in serum klotho; blood and urinary cadmium did not show any statistically significant associations after adjustment (β (95 % CI), p-value for blood cadmium: 0.00 (−0.02–0.01), p = 0.573; urinary cadmium: −0.01 (−0.03–0.01), p = 0.210). Mean serum klotho levels showed a statistically significant decreasing trend with increasing blood lead quartiles (unadjusted and all-adjusted geometric means and 95 % confidence intervals of serum klotho (in pg/mL) for Q1, Q2, Q3, and Q4: unadjusted: 827.49 (814.20–840.92), 811.92 (794.73–829.48), 791.48 (775.11–808.19), and 772.01 (754.23–790.29); adjusted: 830.64 (805.53–856.45), 816.07 (789.18–843.87), 800.71 (773.71–828.57), and 784.31 (757.94–811.59)). Blood lead and levels were negatively associated with serum α-klotho levels in a representative population of US adults. These results suggest that blood lead levels may be associated with the serum levels of a protein associated with cognition and aging. Further research is recommended to investigate the causality behind such relationship.

Association between serum cotinine and α-Klotho levels among adults: Findings from the National Health and Nutrition Examination Survey 2007-2016.

INTRODUCTIONSerum cotinine is a sensitive and specific marker of tobacco smoke exposure. α-Klotho is an anti-ageing molecule, which plays an important role in several diseases. We aimed to examine the association between smoke exposure indicated by the serum cotinine and α-Klotho levels, as previous reports regarding the level of α-Klotho in smokers have been inconsistent.METHODSThis secondary dataset analysis included 9833 participants (aged 40–79 years; 47.0% females and 53.0% males) from the US National Health and Nutrition Examination Survey 2007–2016. Independent variables were serum cotinine level, age, sex, race, body mass index (BMI), and alcohol consumption. The outcome variable was serum α-Klotho level. Multiple linear regression analysis was used to examine the association between serum cotinine and α-Klotho levels.RESULTSThe serum cotinine level was negatively associated with the α-Klotho level (β= -0.107, 95% CI: -0.155 to -0.059, p<0.0001) after adjusting for age, BMI, sex, race, and alcohol consumption. The α-Klotho level in participants with cotinine ≥3 ng/mL decreased by 44.514 pg/mL (p<0.0001) compared to that in participants with cotinine <3 ng/mL. There is a non-linear relationship between serum cotinine and α-Klotho levels. The piecewise linear models indicated a significant threshold effect between serum cotinine and α-Klotho levels. On the left of the inflection point (cotinine <130 ng/mL), the serum cotinine level increased with decreased α-Klotho level (β= -0.519, 95% CI: -0.682 to -0.356). On the right of the inflection point (cotinine ≥130 ng/mL), the serum cotinine level increased with increased α-Klotho level (β=0.085, 95% CI: 0.000 to 0.170).CONCLUSIONSBased on our study results, serum cotinine level was associated with the serum α-Klotho level.

Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients.

IntroductionChronic kidney disease (CKD) has been recognized as a global health problem. Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR).Material and methodsThis was a case-control study consisting of 90 subjects. Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation.ResultsSerum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. (p< 0.01). Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648).ConclusionThe serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. Both serum α-Klotho and oxidative stress were negatively correlated with eGFR in CKD patients. Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR.

MO545: Estimated Proximal Tubule Fluid Phosphate Concentration: An Early Marker of CKD-MBD?

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) typically associates with mineral bone disorders (CKD-MBD), kidney damage progression and increased morbidity and mortality. CKD-MBD develops early in CKD and, if promptly detected, could receive therapeutic attention. However, early markers of CKD-MBD like fibroblast growth factor 23 (FGF23) and α-Klotho are not widely available in clinical practice. Recently, estimated proximal tubule fluid phosphate concentration (ePTFp) has been proposed as a novel early marker of MBD. In fact, in CKD patients, along with the progressive reduction of nephron number, FGF23 increments are necessary to reduce renal tubular phosphate reabsorption and to maintain phosphate balance. As a consequence, PTFp concentration per single nephron progressively increases, leading to renal tubular cells overload, interstitial inflammatory response and progression of kidney damage. For this reason, PTFp concentration could represent an early marker of CKD-MBD. OBJECTIVE To evaluate the relationship between ePTFp and early markers of MBD in patients with CKD stage G2–4. METHOD In CKD patients stage G2–4, we evaluated serum FGF23, α-Klotho, parathyroid hormone (PTH) and ePTFp [ePTFp = (phosphaturia/creatininuria) x creatininemia x 3,33]; 30 healthy subjects (age 40 ± 5 years) were the control group for normal value of ePTFp. RESULTS In 68 CKD patients (age 58.9 ± 15.6 years eGFR 45 ± 21 mL/min), ePTFp averaged 2.4 ± 1.3 mg/mg which was significantly higher than in the control group (ePTFp = 1.2 ± 0.5; P &amp;lt; 0.01). ePTFp increased progressively along with the increasing CKD stages (stage 2: 1.6 ± 0.6; stage 3: 2.3 ± 0.9; stage 4: ± 1.5; P &amp;lt; 0.001) with values significantly higher than the control group since CKD stage 2 (ePTFp: Control group = 1.2 ± 0.5 versus stage 2 = 1.6 ± 0.6; P &amp;lt; 0.05). ePTFp showed a positive correlation with FGF23 (r: 0.69; P &amp;lt; 0.001) and PTH (r:0.310; P &amp;lt; 0.05) and a negative correlation with α-Klotho (r: −237; P &amp;lt; 0.05) and eGFR (r: −647; P &amp;lt; 0.001). CONCLUSION Our data showed early and progressive increments of ePTFp in CKD patients since CKD stage 2. These increments are paralleled by increased FGF23 and PTH and decreased α-Klotho, suggesting reciprocal pathophysiologic dependence. Accordingly, ePTFp could represent a surrogate of renal tubular cells phosphate overload, indicative of CKD-MBD development. ePTFp can be easily obtained in everyday clinical routine and could represent a reference to make therapeutic choices (e.g. dietary phosphate control). In conclusion, ePTFp could identify patients at risk of developing the CKD-MBD maladaptive response with increased risk of kidney damage progression.

Association between serum alpha-Klotho and severe abdominal aortic calcification among civilians in the United States

Background and aimsAbdominal aortic calcification (AAC) has been recognized as an independent predictor of cardiovascular disease (CVD) incidence and mortality. The aim of this cross-sectional study is to investigate the relationship between serum α-Klotho, an anti-aging hormone, and severe AAC in United States (US) civilians, which was not documented before. Methods and resultsThe data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES), which included 2267 individuals aged 40–79 years. Serum α-Klotho concentration, categorized into four quartiles, was examined by enzyme linked immunosorbent assay (ELISA). AAC was quantified by the Kauppila score system based on dual-energy X-ray absorptiometry. The association between serum α-Klotho and severe AAC was determined by multivariable logistic regression models. After adjusting for multiple covariates, the odds ratios (OR) (95% CI) of severe AAC for participants in serum α-Klotho quartiles 2–4 were 0.83 (0.52, 1.32), 0.56 (0.34, 0.94), and 0.54 (0.32, 0.92), respectively, compared with those in quartile 1 (P for trend = 0.007). The association between serum α-Klotho and severe AAC was stable in the different subgroups (all P for interaction＞0.05). ConclusionIn a sample of US adults, serum α-Klotho levels were negatively related to the risk of severe AAC. Our findings indicated that serum α-Klotho may become a promising tool to predict the incidence and prognosis of CVD.

Evaluation of α-klotho, FGF-23 and Insulin Resistance in Obese Prediabetics

Aim: Prediabetes is a condition with hyperglycemia and risk of development type 2 diabetes mellitus (T2DM). The aim of this study is to determine the concentrations of blood pressure, serum lipoproteins, glucose and insulin levels as well as the concentrations of α-klotho and FGF-23 parameters. We also aim at the correlation between all these parameters in obese prediabetics and obese normoglycemics. Material methods: A total of 26 obese normoglycemic (control group) and 25 obese prediabetic individuals were included in this study. Glucose, haemoglobin A1c (HbA1c) and cholesterols levels were analyzed as part of a routine procedure in the biochemistry laboratories of our hospital using an autoanalyzer. In order to determine α-klotho and fibroblast growth factor-23 (FGF-23) levels, ELISA method was used. Result: According to the findings, a significant increase was detected in serum LDL-C, TC, HbA1c, glucose, insulin and HOMA-IR levels in the obese prediabetic group compared to the control group (p <0.05). However, serum α-klotho and FGF-23 levels were found to be significantly lower in the obese prediabetic group compared to the control group (p <0.05). α-klotho and FGF-23 values showed strong negative correlation when compared with HOMA-IR values separately (p <0.01). Conclusion: These findings suggest that α-klotho and / or FGF-23 parameters may be a marker for prediabetes. The results of our study, together with the future studies, will make a significant contribution to the literature, as prediabetes diagnostic criteria in the diabetes outpatient clinics.

The Effects of Cholecalciferol Supplementation on FGF23 and α-Klotho in Hemodialysis Patients With Hypovitaminosis D: A Randomized, Double-Blind, Placebo-Controlled Trial

Vitamin D-fibroblast growth factor-23 (FGF-23)-klotho forms an axis that takes part at least in cardiovascular complications in patients with chronic kidney disease. This study aimed to assess the effects of cholecalciferol supplementation on FGF23 and α-klotho in patients with hypovitaminosis D requiring hemodialysis. In a single-center, parallel-arm, randomized, double-blind, placebo-controlled trial, 86 patients with hypovitaminosis D requiring hemodialysis were enrolled. The patients were randomized into 2 groups (n=43 each) to receive either 50,000 IU of cholecalciferol or placebo every week for 12weeks. Accordingly, the serum levels of FGF23 and klotho were measured by ELISA and compared between both groups. Serum 25OH(D) levels increased in participants who received cholecalciferol supplementation compared with participants who received placebo (P=.006). In addition, serum FGF23 decreased and α-klotho levels increased in the supplemented group compared with placebo. However, the before-after differences between cholecalciferol supplement and placebo were significant only for α-klotho (P=.035). These effects were not accompanied by changes in the levels of phosphate, total and ionized calcium, and intact parathyroid hormone. Cholecalciferol supplementation of 50,000 IU for 12weeks increases α-klotho levels in the serum of kidney failure patients undergoing hemodialysis. This may suggest that patients receiving maintenance hemodialysis can benefit from using cholecalciferol supplementation and increase in serum α-klotho levels.

Potentielle application de l’axe fibroblast growth factor 23-Klotho dans la maladie rénale chronique

Membrane Alpha Klotho (α-klotho) is expressed in the kidney and functions as a co-receptor of FGF receptors (FGFRs) to activate specific fibroblast growth factor 23 (FGF23) signal pathway. FGF23 is produced in bones and participates in mineral homeostasis. The extracellular domain of transmembrane αklotho can be cleaved by proteases and released into the circulation as soluble α-klotho. Klotho deficiency is a pathogenic factor for chronic kidney disease progression and cardiovascular diseases. The FGF23 excess may also contribute to cardiovascular diseases where its pathogenic effect acts via the FGFR4 and independently of α-klotho. The decline in serum α-klotho followed by a rise in serum FGF23 at an early stage of chronic kidney disease can serve as a robust predictor for risk of cardiovascular diseases and mortality in both CKD patients and the general population. The first randomized trials suggest the possibility to reduce FGF23 excess in chronic kidney disease by controlling the phosphate serum using phosphate binders and reducing PTH levels with calcimimetic drug. New strategies emerge, including the administration of α-klotho recombinant and the use of epidrugs in order to correct the klotho deficiency. The FGR4 inhibitors are promising to limit the development of left ventricular hypertrophy linked to FGF23 excess. Finally, a better understanding of the molecular mechanisms of FGF23/α-klotho axis will allow us to find new strategic approaches and improve the CKD patient's management and their outcomes.

Clinical significance of fibroblast growth factor-23 and soluble alpha klotho in different stages of chronic kidney disease

Most chronic kidney disease (CKD) biomarkers in the current clinical use are not sensitive enough and cannot be used to identify the early stage of the disease. Klotho is a transmembrane protein predominantly expressed in the renal tubules and implicated in managing phosphate homeostasis, together with fibroblast growth factor-23 (FGF-23); a bone-derived protein that increases urinary phosphate excretion. The present study was carried out on 50 patients CKD with different etiologies referred to the Internal Medicine Department and Out Patient Clinic of Tanta University Hospitals and 30 apparently healthy individuals of matched age and sex as a control group. They were subjected to the following assessment: detailed history taking, careful clinical examination, and laboratory investigations, including urea, creatinine, estimated glomerular filtration rate (eGFR), serum electrolytes, urinary albumin, urinary phosphorus (U-Ph), and specific laboratory tests for: Alpha Klotho (α-klotho) and FGF-23 by using ELISA technique. The present study shows that the mean value of serum creatinine, urea, phosphorus, urinary albumin, and FGF-23 were significantly increased, whereas there was a significant decrease in the mean value of eGFR, calcium, and U-Ph in the patients with CKD when compared with control group. Plasma level of serum α-klotho is significantly decreased in all patients with CKD when compared to the control group and there was a significant positive correlation between serum α-klotho level and eGFR, serum calcium level and U-Ph level. Plasma level of serum α-klotho is significantly decreased in all patients with CKD and serum α-klotho can be used as a good marker for early diagnosis and staging of CKD.

Bicarbonate Supplement Restores Urinary Klotho Excretion in Chronic Kidney Disease: A Pilot Study

We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum α-Klotho. This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum α-Klotho in these patients. The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age ≥18years, CKD stage 3-5 non dialysis, Sbicar < 22mmol/L, and not receiving bicarbonate supplementation. Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4weeks. Patients were evaluated at two and 4weeks by blood and urine measurements. Mean serum Klotho was 615±287 pg/mL, and mean serum Sbicar was 19.3±1.7mmol/L at baseline. Sbicar increased from baseline at two (23.9±2.9mmol/L, P<.001) and 4weeks (23.4±1.9mmol/L, P<.001). There was no change in serum Klotho at two (630±333mmol/L) and 4weeks (632±285mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6±31.6 pg/mmoL), increased by 320% at two weeks (P<.005) and by 280% at 4weeks (P<.01). Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble α-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum α-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD.

Serum αKlotho as a Predictor of Graft Dysfunction After Kidney Transplantation

ObjectiveTo improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. MethodsPlasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). ResultsThe median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. ConclusionMeasurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.

Differential expression of serum biomarkers in hemodialysis patients with mild cognitive decline: A prospective single-center cohort study

Studies suggest that hemodialysis patients are at a higher risk for cognitive decline than healthy individuals; however, underlying mechanisms have not been fully elucidated. We aimed to investigate the roles of serum biomarkers, such as brain-derived neurotrophic factor (BDNF), inflammatory cytokines, fibroblast growth factor (FGF)-23 and its co-receptor α-klotho and platelet (PLT) count in mild cognitive decline (MCD) of patients undergoing hemodialysis in this prospective cohort study. Serum levels of BDNF, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and the number of PLT were significantly altered in the MCD group compared with those in healthy controls (HCs) or those with normal cognitive function (NCF). Although serum α-klotho and FGF-23 levels were significantly altered in the MCD group, there were no statistical differences between the MCD and NCF groups. Serum BDNF levels and PLT counts were significantly correlated with cognitive test scores. Receiver operating characteristic (ROC) curves demonstrated that BDNF and PLT were potential biomarkers for improved MCD diagnosis in patients with hemodialysis. These findings suggest that hemodialysis-related MCD is associated with altered BDNF, TNF-α and IL-6 levels as well as PLT counts and that serum BDNF levels and PLT counts are potential biomarkers for hemodialysis-related MCD diagnosis.

High-intensity physical exercise increases serum α-klotho levels in healthy volunteers

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Evaluation of serum soluble klotho protein in patients with different degrees of chronic kidney disease

Objectives The aim of this study was to investigate serum α-klotho as a new biomarker for the diagnosis of chronic kidney disease (CKD), especially in its early stages. Background α-Klotho is a novel antiaging protein that was identified as a regulator of calcium and phosphate homeostasis, which is highly expressed in the kidney. The soluble form of klotho acts as an endocrine substance that exerts multiple actions including the modulation of renal solute transport and protection of the kidney. Methods A case–control study was conducted at the Clinical Pathology Department, Menoufia University Hospitals, Faculty of Medicine, during the period from January 2015 to November 2016. Sixty-eight patients suffering from CKD who were admitted to the hospital during the period from January 2015 to November 2016 were included in this study. In addition, 10 apparently healthy subjects with matching age and gender formed the control group. Routine laboratory investigations performed were: hemoglobin, urea, creatinine, uric acid, calcium (Ca2), phosphate (PO4), and albumin and the estimated glomerular filtration rate were measured and the α-klotho protein level was measured by ELISA. Results Serum soluble α-klotho protein levels were significantly lower in CKD patients compared with normal controls. Besides, α-klotho protein levels were positively correlated with estimated glomerular filtration rate, hemoglobin and were negatively correlated with renal function tests and phosphate. Conclusion Soluble α-klotho levels are significantly decreased in CKD not only in the advanced stages but also in the early stages.

Clinical implication of alterations in serum Klotho levels in patients with type 2 diabetes mellitus and its associated complications

AimTo investigate the clinical significance of serum α-Klotho and β-Klotho levels in patients with type 2 diabetes mellitus (T2DM) and its associated complications. MethodsSerum α-Klotho and β-Klotho levels were measured using an ELISA kit in 817 individuals, including 127 with T2DM, 106 with diabetic nephropathy, 99 with diabetic retinopathy, 108 with diabetic neuropathy, 102 with diabetic foot disease, 135 with T2DM and more than one complication and 140 healthy controls. ResultsBoth α-Klotho and β-Klotho levels were significantly decreased in the T2DM group and the groups with associated complications compared with the levels in control group. The differences between the T2DM group and the T2DM with complications groups were not significant, except between the diabetic nephropathy group and the other diabetic complications groups. In addition, α-Klotho and β-Klotho levels were negatively correlated with serum fructosamine and HbA1c but were not associated with serum glucose in the model including all participants. Moreover, decreases in α-Klotho and β-Klotho levels in the high glucose-exposed cell culture model, which was dependent on glucose exposure time, were confirmed. ConclusionsLevels of α-Klotho and β-Klotho were downregulated in patients in the T2DM and complications groups. Our findings indicate that serum Klotho levels were associated with the development of T2DM, and long-term control of blood glucose will be beneficial in ameliorating changes to α-Klotho and β-Klotho levels in patients with T2DM and complications.

High-intensity physical exercise increases serum α-klotho levels in healthy volunteers.

The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated. A standard Bruce protocol treadmill exercise was undertaken by 10 fasting healthy volunteers. sKl, sPi, and blood glucose levels were measured in samples collected 1-week prior, immediately pre (T pre), 0 (T post), 30 (T 30), 240 (T 240) min, and 1-week after exercise. Median (interquartile range) age of participants was 47.5 (44–51) years; five (50%) were male. All study participants achieved at least 90% predicted maximum heart rate (MHR). sKl increased acutely after exercise (T pre median 448 pg/mL vs. T post median 576 pg/mL; p < 0.01). There was a nonsignificant sPi decline at T 30 (T pre 0.94 ± 0.12 mmol/L vs. T 30 0.83 ± 0.22 mmol/L). Exercise led to a reduction in blood glucose by T 240 with median glucose levels at T pre, T post, T 30, and T 240 of 6.0, 6.5, 6.3, and 5.7 mmol/L, respectively. In conclusion, a single high-intensity exercise session is associated with a transient increase in sKl, a delayed reduction in blood glucose, and a nonsignificant decrease in sPi levels in healthy adults. The evaluation of long-term effects of cardiovascular fitness programs on sKl and sPi in healthy individuals and disease cohorts are required to identify potential lifestyle modifications to help improve chronic disease management and long-term outcomes.

Endothelin-1, α-Klotho, 25(OH) Vit D levels and severity of disease in scleroderma patients.

Considering the role of endothelin-1 (ET-1) in tissue remodeling and fibrosis during the development of scleroderma as well as the effect of α-Klotho in pathogenesis of calcinosis and/or endothelial cell injury and its correlation with severity of disease, this study aimed to evaluate serum ET-1, α-Klotho and 25(OH) vitamin D levels in patients with limited and diffuse scleroderma compared to healthy subjects. In this cross-sectional study, 60 scleroderma patients according to the ACR/EULAR 2013 criteria and 60 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and Medsger severity scale was assessed. Serum ET-1, soluble α-Klotho and 25(OH)D3 levels were measured using ELISA kits. The mean±SD age of patients and controls was 46.2±9.6 and 47.2±7.0years, respectively. Compared to healthy controls, serum ET-1 was significantly higher in SSc patients (p=0.001); whilst serum α-Klotho and 25(OH)D3 were significantly lower in patients (p=0.001). The most common organs involved in patients were skin, lung, peripheral vascular and gastrointestinal system and the severity of involvement was mainly mild and/or moderate. There were no significant differences in serum ET-1 and α-Klotho levels according to the severity of different organ involvement (p>0.05). There was no significant correlation between presence or absence of calcinosis and negative or positivity of auto-antibodies with ET-1, α-Klotho and 25(OH)D3 levels. Although our study revealed higher serum ET-1 and lower serum α-Klotho levels in SSc patients compared to healthy controls, there were not any significant correlations between their serum levels with severity of organ involvement.