Soluble Klotho Levels Research Articles

Association between the triglyceride–glucose index and serum soluble Klotho in middle-aged and older adults from NHANES 2007–2016

Klotho, an anti-aging protein, is believed to participate in metabolic diseases and play a potential protective role by regulating insulin sensitivity. This study aimed to explore the relationship between the triglyceride-glucose (TyG) index (a simple marker of insulin resistance) and serum soluble Klotho (S-Klotho) levels. The cross-sectional study comprised 5237 adults aged 40–79 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The serum levels of S-Klotho were measured by enzyme-linked immunosorbent assay. The association between the TyG index and S-Klotho levels was investigated by multiple linear regression models, smoothed curve fitting, segmented linear regression models, subgroup analyses, and interaction tests. The TyG index was inversely associated with serum S-Klotho level after full adjustment (β = − 45.11, 95% CI (− 79.53, − 10.69), P = 0.011). Furthermore, we also found a non-linear correlation and saturation phenomenon between the TyG index and serum S-Klotho levels, with a turning point of 9.56. In addition, a significant interaction effect of sex was found between the two (P for interaction < 0.001), with a more pronounced association observed in females. Further studies are required to explore the mechanisms and verify the correlation.

Retracted: Composite Dietary Antioxidant Index and Plasma Levels of Soluble Klotho: Insights from NHANES.

[This retracts the article DOI: 10.1155/2023/3524611.].

Aging and antioxidants: the impact of dietary carotenoid intakes on soluble klotho levels in aged adults.

The association between dietary carotenoid intake and Soluble Klotho (S-Klotho) levels among the elderly population requires further evaluation. The purpose of this study is to evaluate the relationship between the dietary carotenoid intake and the S-Klotho plasma levels in older adults. Eligible participants aged 60 years or above were selected from the National Health and Nutrition Examination Surveys (NHANES) data, collected between 2007 and 2016. The consumption of carotenoids was determined through two 24-hour dietary recall assessments. Moreover, the S-Klotho levels in the serum were measured using an Enzyme-Linked Immuno-Sorbent Assay (ELISA). A total of 5,056 participants were included in the study having a median total carotenoid intake of 9775.25 μg (95% confidence interval (CI): 8971.30-10579.21) and a median S-Klotho concentration of 815.59 pg/mL (95% CI: 802.59-828.60). The multivariable regression analysis showed that a single standard deviation increase in total carotenoid intake was significantly associated with an 8.40 pg/mL increase in S-Klotho levels (95% CI: 0.48-16.31). When the carotenoids were divided into quartiles, participants in the third ((4963.5μg/day,11662.5μg/day]) and fourth quartiles ((11662.5μg/day,377178μg/day]) showed higher S-Klotho levels compared to those in the first quartile. Among carotenoid subtypes, increased intake of α-carotene, β-carotene, and lutein with zeaxanthin was associated with elevated S-Klotho levels. These observed associations between carotenoid subtypes and S-Klotho levels remained consistent across male participants, having a normal weight, and a moderate physical activity based on stratified analysis. The total carotenoid intake was positively related to plasma levels of S-Klotho in the elderly population, particularly for α-carotene, β-carotene, and lutein with zeaxanthin. However, further research is needed to confirm these findings and explore the underlying mechanisms behind this relationship.

Lower serum Klotho level and higher systemic immune-inflammation index: an inverse correlation

ObjectivesKlotho, an anti-aging protein, has been identified to control tissue inflammatory responses. The objective of this research is to determine the linkage between soluble Klotho (S-Klotho) level and systemic immune-inflammation index (SII).MethodsEligible participants with complete information of S-Klotho level and SII were selected from the National Health and Nutrition Examination Surveys (NHANES). Subsequently, weighted multivariate linear regression and subgroup analysis were carried out to evaluate the association.ResultsTotally, 11,108 adults with complete data on S-Klotho level, SII and other important covariates were included in final analysis. Multivariate liner regression revealed that high level of S-Klotho was associated with low level of SII after multivariate adjustments (β=-0.08, 95%CI:-0.10- -0.05, P < 0.01). When classifying S-Klotho into tertiles, participants in S-Klotho tertile 3 (Q3) showed a decrease in SII level compared with those in the lowest tertile (Q1) (β=-45.44, 95%CI:-64.41- -26.47, P < 0.01 ). The negative associations remained significant regardless of age and gender, and varied depending on smoking status and BMI subgroups.ConclusionS-Klotho level was negatively related to SII after controlling for covariates. Further studies need to validate current findings and explore the fundamental mechanisms.

Improving sleep quality is essential for enhancing soluble Klotho levels in hemodialysis patients.

Sleep and Klotho seem to share common physiological pathways in aging. However, studies investigating this relationship are very few and none of them was done with a specific patient group. The aim of this study was to investigate the association of sleep quality and soluble Klotho levels in hemodialysis patients. 100 hemodialysis patients were included in this study. Soluble Klotho levels were obtained from each patient and Pittsburgh Sleep Quality Index was performed by all patients. Association of soluble Klotho with sleep quality was calculated. Soluble Klotho levels were significantly inversely correlated with total sleep quality score (p < 0.001, r = -0.444). Among the subscales, soluble Klotho levels were negatively correlated with subjective sleep quality (p < 0.001, r = -0.365), sleep latency (p = 0.002, r = -0.312), sleep disturbance (p = 0.002, r = -0.303) and daytime dysfunction (p = 0.027, r = -0.221). Patients who had good sleep quality scores were found to have higher soluble Klotho levels [4.15 (0.05-22.68) vs. 1.14 (0.32-17.63), p < 0.001]. In regression analysis, total sleep quality score, subjective sleep quality and age were found to be independent negative factors for soluble Klotho levels. In this study, a significant association between sleep quality and soluble Klotho levels was revealed in hemodialysis patients. Improving sleep quality will lead to increased soluble Klotho levels, which may further slow down the aging process in hemodialysis patients.

#5642 ASSOCIATION BETWEEN FIBROBLAST GROWTH FACTOR 23 AND TRABECULAR BONE SCORE IN EARLY STAGES OF CKD

Abstract Background and Aims Newer markers of kidney damage and mineral and bone changes in chronic kidney disease (CKD) are needed. The fracture risk increases with worsening of CKD with highest incidence in later stages. Thus methods for early bone status assessment and laboratory marker of kidney function is needed. Aim of the study was to evaluate bone mineral density (BMD) and trabecular bone score (TBS) – a novel surrogate of trabecular bone microstructure, in relationship with newer laboratory markers of CKD, such as fibroblast growth factor 23 (FGF23) and klotho. Method A cross-sectional study during July 2018-July2019 was conducted. Plasma levels of soluble klotho and FGF23 were determined by ELISA (enzyme-linked immuno -assay). All patients undergone bone mineral density (BMD) and trabecular bone scores (TBS) measurement. Patients were divided into 2 groups as follows: A - patients in stages G1 - G3; B - patients in stages G4 – 5 accoridng to KDIGO. Results A total of 74 CKD patients (42 males and 32 females; mean age 68.8 years) were included in the study. Greater FGF23 levels in group B(N = 15) in comparison to group A (N = 59)(p = .001) were observed. FGF23 was associated with glomerular filtration (GF)(R = -0.43; p = 0.003), with greater levels of FGF23 at GF less than 0.8 ml/s. Significant difference in TBS within first 3 CKD stages (mean TBS in G1 = 1.374 vs. G2 = 1.304 vs. G3a = 1.24; p = 0.03) and negative correlation of FGF23 and TBS (R = -0.33; p = 0.05) and a positive correlation between klotho and TBS (R = 0.419; p = 0.04) was observed. Conclusion This study confirmed that FGF23 is associated with TBS. However, TBS reflects kidney function decline only in first 3 stages of CKD. Thus, FGF23 together with TBS are promising markers of early trabecular bone impairment in CKD.

Neuroprotective Role of Klotho on Dementia.

Klotho, a gene found on chromosome 13q12, is involved in a variety of processes and signaling pathways in the human body related to vitamin D metabolism; cardiovascular, renal, musculoskeletal, and skin diseases; and cancer biology. However, more importantly, it has been linked to beneficial effects related to anti-aging. The levels of soluble Klotho in the blood have been found to decline with age, increasing the risk of age-related diseases. When the Klotho gene was silenced or defective, it caused a shorter lifespan. However, when the gene was overexpressed, it resulted in a longer lifespan. Klotho has positive benefits on the neurological system by causing a higher representation of useful longevity genes, preventing further neuronal damage, and offering neuroprotection. Thus, it has the potential to become a new treatment for many age-related diseases that cause dementia, including multiple sclerosis, Alzheimer's disease, and Parkinson's disease.In this review, we discuss the mechanisms of Klotho's benefits and roles on various organ systems, specifically on nervous system disorders that lead to dementia.

Klotho inversely relates with carotid intima- media thickness in atherosclerotic patients with normal renal function (eGFR ≥60 mL/min/1.73m2): a proof-of-concept study.

Klotho protein is predominantly expressed in the kidneys and has also been detected in vascular tissue and peripheral blood circulating cells to a lesser extent. Carotid artery intima-media thickness (CIMT) burden, a marker of subclinical atherosclerosis, has been associated with reductions in circulating Klotho levels in chronic kidney disease patients, who show reduced levels of this protein at all stages of the disease. However, the contribution of serum Klotho and its expression levels in peripheral blood circulating cells and in the carotid artery wall on the CIMT in the absence of kidney impairment has not yet been evaluated. We conducted a single-center study in 35 atherosclerotic patients with preserved kidney function (eGFR≥60 mL/min/1.73m2) subjected to elective carotid surgery. Serum levels of Klotho and cytokines TNFa, IL6 and IL10 were determined by ELISA and transcripts encoding for Klotho (KL), TNF, IL6 and IL10 from vascular segments were measured by qRT-PCR. Klotho protein expression in the intima-media and adventitia areas was analyzed using immunohistochemistry. APatients with higher values of CIMT showed reduced Klotho levels in serum (430.8 [357.7-592.9] vs. 667.8 [632.5-712.9] pg/mL; p<0.001), mRNA expression in blood circulating cells and carotid artery wall (2.92 [2.06-4.8] vs. 3.69 [2.42-7.13] log.a.u., p=0.015; 0.41 [0.16-0.59] vs. 0.79 [0.37-1.4] log.a.u., p=0.013, respectively) and immunoreactivity in the intimal-medial area of the carotids (4.23 [4.15-4.27] vs. 4.49 [4.28-4.63] log µm2 p=0.008). CIMT was inversely related with Klotho levels in serum (r= -0.717, p<0.001), blood mRNA expression (r=-0.426, p=0.011), and with carotid artery mRNA and immunoreactivity levels (r= -0.45, p=0.07; r= -0.455, p= 0.006, respectively). Multivariate analysis showed that serum Klotho, together with the gene expression levels of tumor necrosis factor TNFa in blood circulating cells, were independent determinants of CIMT values (adjusted R2 = 0.593, p<0.001). The results of this study in subjects with eGFR≥60mL/min/1.73m2 show that patients with carotid artery atherosclerosis and higher values of CIMT present reduced soluble Klotho levels, as well as decreased KL mRNA expression in peripheral blood circulating cells and Klotho protein levels in the intima-media of the carotid artery wall.

Individual nutrients and serum klotho levels in adults aged 40-79 years.

Several dietary factors (including adherence to the Mediterranean diet or higher nut intake) seem to positively affect circulating antiaging Klotho protein levels; yet, a description of possible relationships between individual nutrients and Klotho activity has not been evaluated. We analyzed the association of dietary intake of individual macro- and micronutrients and nonnutritive food components with circulating Klotho levels in a sample of 40- to 79-year-old US adults. Data from the 2015-2016 National Health and Nutrition Examination Survey were analyzed. Nutrient/food component intakes were calculated in relation to total energy intake using the nutrient density method, and available pristine serum samples were analyzed for serum Klotho concentrations. The final study sample consisted of 2637 participants (mean age 59.0 ± 10.7 years; 52% women). Higher Klotho concentrations were found with higher intake of carbohydrates (p < .001), total sugars (p < .001), dietary fibers (p < .001), vitamin D (p=.05), total folates (p=.015), and copper (p=.018). The results of the regression analysis with a crude model showed significant associations among five nutrients/food components (carbohydrates, alcohol, total sugars, dietary fibers, and niacin) and soluble Klotho levels across the sample. After adjusting the models for age and gender, the nutrient/food component-Klotho association remained significant for carbohydrates, total sugars, and alcohol (p < .05). Dietary exposure to individual nutrients and nonnutritive food components appears to be associated with Klotho activity; however, additional research is needed to investigate the relationship between cause and effect in diet composition-Klotho interplay.

Soluble Klotho protects against glomerular injury through regulation of ER stress response

αKlotho (Klotho) has well established renoprotective effects; however, the molecular pathways mediating its glomerular protection remain incompletely understood. Recent studies have reported that Klotho is expressed in podocytes and protects glomeruli through auto- and paracrine effects. Here, we examined renal expression of Klotho in detail and explored its protective effects in podocyte-specific Klotho knockout mice, and by overexpressing human Klotho in podocytes and hepatocytes. We demonstrate that Klotho is not significantly expressed in podocytes, and transgenic mice with either a targeted deletion or overexpression of Klotho in podocytes lack a glomerular phenotype and have no altered susceptibility to glomerular injury. In contrast, mice with hepatocyte-specific overexpression of Klotho have high circulating levels of soluble Klotho, and when challenged with nephrotoxic serum have less albuminuria and less severe kidney injury compared to wildtype mice. RNA-seq analysis suggests an adaptive response to increased endoplasmic reticulum stress as a putative mechanism of action. To evaluate the clinical relevance of our findings, the results were validated in patients with diabetic nephropathy, and in precision cut kidney slices from human nephrectomies. Together, our data reveal that the glomeruloprotective effects of Klotho is mediated via endocrine actions, which increases its therapeutic potential for patients with glomerular diseases.

Composite Dietary Antioxidant Index and Plasma Levels of Soluble Klotho: Insights from NHANES.

The association between dietary antioxidants and soluble Klotho (S-Klotho) levels remains unknown. We investigated to explore whether the composite dietary antioxidant index (CDAI) was associated with serum levels of S-Klotho in the middle-aged population. Eligible participants were identified from the National Health and Nutrition Examination Surveys (NHANES) from 2007 until 2016. The CDAI was calculated from the intake of six dietary antioxidants. The serum levels of S-Klotho were measured via enzyme-linked immunosorbent assay (ELISA). Generalized linear and nonlinear models were established to analyze the relationship between CDAI and S-Klotho levels. Based on the S-Klotho quartiles, S-Klotho levels were higher in young women, Blacks, higher education, never smokers, lower waistlines, no medication use, and those with higher CDAI. Univariate analysis revealed that age, gender, race, smoking status, body mass index, waistline, and medication use were associated with serum levels of S-Klotho. When potential confounders were controlled, CDAI was significantly associated with S-Klotho levels. Subgroup analysis also revealed that this association remained significant in individuals who had the highest quartiles of CDAI, aged population (>60 years), male, and never smoker. A nonlinear relationship was observed between the CDAI and S-Klotho plasma concentrations. CDAI was positively correlated with plasma levels of S-Klotho after controlling for covariates. Further studies are needed to validate the current findings and explore the fundamental mechanisms.

PS-BPC11-4: LOW SOLUBLE KLOTHO IS ASSOCIATED WITH RESISTANT HYPERTENSION IN CKD: FROM THE KNOW-CKD STUDY

Objective: Apparent treatment-resistant hypertension (ATRH) is highly prevalent in chronic kidney disease (CKD) and is a risk factor for rapid progression of CKD. Soluble klotho is an extracellular domain of klotho released into the circulation. Although soluble klotho is known to be a risk factor for hypertension, the association between soluble klotho and ATRH is unknown. The aim of this study is to evaluate the association of soluble klotho with ATRH in CKD. Design and method: In this cross-sectional study, we analyzed 1,737 predialysis CKD patients enrolled in the prospective Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). Apparent treatment-resistant hypertension was defined as systolic blood pressure &gt; = 140 mm Hg or diastolic blood pressure &gt; = 90 mm Hg with concurrent use of three antihypertensive medication classes or use of four or more antihypertensive medication classes regardless of blood pressure level. Serum klotho levels were measured using an enzyme-linked immunosorbent assay. Participants were divided into quartiles. Results: Among study subjects, 303 patients (17.4%) had ATRH. Prevalence of ATRH were 21.9%, 18.9%, 18.2% and 10.8% for the 1st to 4th quartiles of soluble klotho, respectively (p for trend &lt; 0.001). The adjusted OR [95% CI] of 1st to 3th quartile of soluble klotho in reference to 4th quartile were 2.01 (1.32–3.06), 1.59 (1.04–2.42) and 1.69 (1.11–2.57). Conclusions: Soluble klotho level was inversely associated with the presence of ATRH in Korean predialysis CKD patients. This relationship was independent of various cardiovascular risk factors.

S-38-1: EPIGENETIC MECHANISM OF SALT-SENSITIVE HYPERTENSION

Nutritional and environmental factors contribute to the development of salt sensitive hypertension. DNA methylation, the most extensively studied epigenetic marker, may have more stable, longer lasting effects than transient changes in gene expression. Protein malnutrition during pregnancy causes prenatal programmed salt sensitive hypertension via aberrant DNA methylation of the angiotensin receptor, which is induced by exposure to excessive glucocorticoid in the fetal hypothalamus. In adults, salt sensitive hypertension induced by obesity is attributable to increased renal activity of Rac1 and mineralocorticoid receptor (MR) pathway, and adverse prenatal exposure induces transgenerational hypertension through activation of Rac1 and MR pathway by an epigenetic regulated mechanism. Finally, DNA methylation of Klotho in aged kidneys leads to a reduction in the circulating levels of soluble Klotho, and in turn, resulting in the activation of noncanonical Wnt5a and RhoA signaling in the vasculature and the development of aging associated salt sensitive hypertension. These findings indicate that epigenetic modulation has an important role in the development of salt sensitive hypertension throughout life.

Recent Advances in Hypertension: Epigenetic Mechanism Involved in Development of Salt-Sensitive Hypertension.

This review highlights recent insights into the epigenetic mechanism of salt-sensitive hypertension from the fetus to the elderly population, mainly focusing on the DNA methylation and histone modification-mediated regulation of hypertension-associated genes. Maternal malnutrition during pregnancy induces upregulation of AT1a (angiotensin receptor 1a) by aberrant DNA methylation, and increased AT1A activity in the hypothalamus develops prenatally programmed salt-sensitive hypertension through renal sympathetic overactivity. In addition, maternal lipopolysaccharide exposure during pregnancy induces upregulation of the Rac1 gene through histone modification by H3K9me2 across generations, resulting in salt-induced activation of the Rac1-MR (mineralocorticoid receptor) pathway in the kidney and the development of salt-sensitive hypertension in F4 and F5 offspring. In mice, aberrant DNA methylation of the Klotho gene, which regulates aging-associated hypertension, decreases the circulating soluble Klotho levels, leading to activation of the vascular Wnt5a-RhoA pathway and vasoconstriction and development of salt-sensitive hypertension because of decreased renal blood flow. A detailed understanding of the environmentally-induced epigenetic modulations related to salt-induced hypertension could be promising for developing preventive and therapeutic approaches to hypertension.

Serum biomarkers of colonic polyps in patients with acromegaly: a meta-analysis and systematic review.

In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly. We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0. Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p < 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p < 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p < 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p > 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p > 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels. We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.

Association between serum klotho levels and cardiovascular disease risk factors in older adults

BackgroundKlotho deficiency is a significant predictor of cardiovascular disease (CVD)-related mortality and morbidity. However, research assessing the association between klotho and individual risk factors of CVD is limited. This study aimed to explore the association between circulating serum klotho levels and risk factors for CVD in adults.MethodsWe used the 2007–2016 National Health and Nutrition Examination Survey and included 13,154 participants for whom serum klotho levels were available. Body mass index (BMI), exercise, smoking status, alcohol consumption, hypertension, dyslipidemia, serum lipid parameters, and blood pressure were considered as CVD risk factors.ResultsCirculating klotho levels were negatively associated with being overweight (beta coefficient: − 22.609, p = 0.0025), obesity (beta coefficient: − 23.716, p = 0.0011), current smoking (beta coefficient: − 46.412, p < 0.0001), and alcohol consumption (beta coefficient: − 51.194, p < 0.0001). There was a positive association between serum klotho levels and no history of dyslipidemia (beta coefficient: 15.474, p = 0.0053). Serum klotho levels were significantly decreased by a unit increase in triglycerides (beta coefficient: − 0.117, p = 0.0006) and total cholesterol (beta coefficient: − 0.249, p = 0.0002). There was a significant non-linear relationship between serum klotho levels, triglycerides, and total cholesterol.ConclusionsLower serum klotho levels are associated with certain CVD risk factors, including high BMI, smoking, alcohol consumption, and lipid parameters (triglycerides and total cholesterol). This study suggests that the soluble klotho level may be a potential marker for CVD risk.

The association between serum soluble Klotho and chronic kidney disease among us adults ages 40 to 79 years: Cross-sectional study.

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.

Adherence to Mediterranean Diet and Soluble Klotho Level: The Value of Food Synergy in Aging.

Diets for healthy aging have long been an intriguing issue. The current study makes a head-to-head comparison of four dietary patterns and their associations with soluble Klotho (s-Klotho) levels, an aging-related marker. The dietary data of 7906 subjects were obtained from the National Health and Nutrition Examination Survey 2007–2016. Each participant was given a score or was grouped according to four dietary patterns, namely the Mediterranean adherence diet score (MDS), the low-carbohydrate-diet score, a low-fat diet, and a low-carbohydrate diet. Subsequently, the associations with s-Klotho were examined using linear regression analyses. In addition, we calculated the odds ratio (OR) for aging in different dietary patterns, taking the lowest quartile of s-Klotho as a reference for aging. The MDS was the only dietary pattern that revealed a relationship with s-Klotho levels. The positive association (β coefficient: 9.41, p < 0.001) remained significant when dividing the MDS into tertiles (Tertile 2: β coefficient: 36.87, p < 0.001; Tertile 3: β coefficient: 45.92, p < 0.001) and grouping participants into subsets by sex, age, and BMI. A lower OR for aging was observed in higher MDS groups (Tertile 2: OR = 0.86, p = 0.026; Tertile 3: OR = 0.77, p < 0.001). However, when analyzed separately, merely three out of nine components of the MDS, namely alcohol consumption (β coefficient: 42.54, p < 0.001), fruit (β coefficient: 11.59, p = 0.029), and dairy products (β coefficient: 8.55, p = 0.032), showed a significant association with s-Klotho. The Mediterranean diet adopts a food-based approach, which has the merit of valuing the complex interactions between foods and their constituents, and further brings benefits to healthy aging.

The association of soluble Klotho levels with anemia and hemoglobin variability in hemodialysis patients.

The anti-aging protein Klotho levels are decreased, and Klotho deficiency is associated with cardiovascular diseases in patients with chronic kidney disease. There are recent studies about the relation between soluble Klotho levels and anemia. We aimed to investigate the correlation of anemia and hemoglobin variability with soluble Klotho levels in hemodialysis patients. Ninety-one hemodialysis patients were included in this study. The mean hemoglobin value, hemoglobin variability, and coefficient of variation of hemoglobin for each patient were calculated. According to mean hemoglobin levels, two groups were defined as under 11 and ≥11 g/dl. Soluble Klotho levels of each patient were studied. Mean hemoglobin levels, hemoglobin variability, and coefficient of variation of hemoglobin were not significantly correlated with soluble Klotho levels. According to mean hemoglobin levels under 11 and ≥ 11 g/dl, there was no statistically significant correlation between anemia and soluble Klotho levels. Soluble Klotho levels were not associated with anemia and hemoglobin variability in hemodialysis patients. Further studies are needed to reveal the complicated relation between anemia and soluble Klotho levels.

Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

BackgroundWe aimed to evaluate soluble Klotho and circulating fibroblast growth factor 23 (FGF23) ratio as a risk factor for renal progression, cardiovascular (CV) events, and mortality in chronic kidney disease (CKD).MethodsWe analyzed 2,099 subjects from a CKD cohort whose soluble Klotho and C-terminal FGF23 levels were measured at enrollment. The Klotho to FGF23 ratio was calculated as Klotho values divided by FGF23 values + 1 (hereinafter called the Klotho/FGF23 ratio). Participants were categorized into quartiles according to Klotho/FGF23 ratio. The primary outcome was renal events, defined as the doubling of serum creatinine, 50% reduction of estimated glomerular filtration rate from the baseline values, or development of end-stage kidney disease. The secondary outcomes consisted of CV events and death. Changes in CV parameters at the time of enrollment and during follow-up according to the Klotho/FGF23 ratio were also examined.ResultsDuring the follow-up period of 64.0 ± 28.2 months, 735 (35.1%) and 273 (13.0%) subjects developed renal events and composite outcomes of CV events and death, respectively. After adjustment, the first (HR: 1.36; 95% CI: 1.08–1.72, P = 0.010) and second (HR: 1.45; 95% CI: 1.15–1.83, P = 0.002) quartiles with regard to the Klotho/FGF23 ratio showed elevated risk of renal events as compared to the fourth quartile group. There was no significant association between Klotho/FGF23 ratio and the composite outcome of CV events and death. The prevalence of left ventricular hypertrophy and vascular calcification was higher in the low Klotho/FGF23 ratio quartiles at baseline and at the fourth-year follow-up.ConclusionsLow Klotho/FGF23 ratio was significantly associated with increased renal events in the cohort of Korean predialysis CKD patients.