Serum Endocan Is a Risk Factor for Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis.

Background and Objectives: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and angiogenesis. We aimed to investigate the link between endocan and aortic stiffness in maintenance hemodialysis (HD) patients. Materials and Methods: After recruiting HD patients from a medical center, their baseline characteristics, blood sample, and anthropometry were assessed and recorded. The serum endocan level was determined using an enzyme immunoassay kit, and carotid-femoral pulse wave velocity (cfPWV) measurement was used to evaluate aortic stiffness. Results: A total of 122 HD patients were enrolled. Aortic stiffness was diagnosed in 53 patients (43.4%), who were found to be older (p = 0.007) and have a higher prevalence of diabetes (p < 0.001) and hypertension (p = 0.030), higher systolic blood pressure (p = 0.011), and higher endocan levels (p < 0.001), when compared with their counterparts. On the multivariate logistic regression model, the development of aortic stiffness in patients on chronic HD was found to be associated with endocan [odds ratio (OR): 1.566, 95% confidence interval (CI): 1.224-2.002, p < 0.001], age (OR: 1.040, 95% CI: 1.001-1.080, p = 0.045), and diabetes (OR: 4.067, 95% CI: 1.532-10.798, p = 0.005), after proper adjustment for confounders (adopting diabetes, hypertension, age, systolic blood pressure, and endocan). The area under the receiver operating characteristic curve was 0.713 (95% CI: 0.620-0.806, p < 0.001) for predicting aortic stiffness by the serum endocan level, at an optimal cutoff value of 2.68 ng/mL (64.15% sensitivity, 69.57% specificity). Upon multivariate linear regression analysis, logarithmically transformed endocan was proven as an independent predictor of cfPWV (ß = 0.405, adjusted R2 change = 0.152; p < 0.001). Conclusions: The serum endocan level positively correlated with cfPWV and was an independent predictor of aortic stiffness in chronic HD patients.

Association of endothelial dysfunction and peripheral arterial disease with sarcopenia in chronic kidney disease.

BACKGROUND: Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non-dialysis CKD. METHODS: This cross-sectional study included 420 patients with stages 3-5 non-dialysis CKD aged 69.0 ± 11.8 years. Skeletal muscle index (skeletal muscle mass/height2), handgrip strength, 6-m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle-brachial index (ABI), respectively. A VRI < 1.0 was classified as poor endothelial function, and an ABI < 0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine, endothelin-1 (ET-1) and interleukin-6, were measured in a subgroup of 262 patients. RESULTS: Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04 ± 0.16 vs. 1.08 ± 0.15, P = 0.028 for the right ABI; 1.01 ± 0.16 vs. 1.06 ± 0.16, P = 0.002 for the left ABI) and VRI (0.83 ± 0.57 vs. 1.08 ± 0.56, P < 0.001) and had higher serum levels of ICAM-1 (P < 0.001), VCAM-1 (P = 0.003) and ET-1 (P = 0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio [OR]: 0.81/0.1 increase; 95% confidence interval [CI]: 0.67-0.98; P = 0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88-0.98; P = 0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM-1 (OR: 2.47/1-SD increase; 95% CI: 1.62-3.75) and VCAM-1 (OR: 1.91/1-SD increase; 95% CI: 1.27-2.87) were independent predictors of sarcopenia. Group stratification based on the cut-offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69-10.49), compared with those with normal VRI and ABI. CONCLUSIONS: Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3-5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.

Novel equations incorporating the sarcopenia index based on serum creatinine and cystatin C to predict appendicular skeletal muscle mass in patients with nondialysis CKD.

BACKGROUND & AIMS: Skeletal muscle mass measurements are important for customizing nutritional strategies for patients with chronic kidney disease (CKD). The serum creatinine-to-cystatin C ratio (Cr/CysC) is a potential indicator of sarcopenia. We developed simple equations to predict the appendicular skeletal muscle mass (ASM) of patients with CKD using readily available parameters and Cr/CysC. METHODS: Overall, 573 patients with nondialysis CKD stages 3-5 were included for developing and validating the equations. The participants were randomly divided into development and validation groups in a 2:1 ratio. ASM was measured using the Body Composition Monitor (BCM), a multifrequency bioelectrical impedance spectroscopy device. The height, weight, anthropometric data, and handgrip strength (HGS) of the participants were obtained. Equations were generated using stepwise multiple linear regression models. The prognostic significance of the predicted ASM was evaluated in a CKD registry comprising 1043 patients. RESULTS: The optimal equation without anthropometric data and HGS (Equation 1) was as follows: ASM (kg) = -7.949 - 0.049 × Age (years) - 2.213 × Woman + 0.090 × Height (cm) + 0.210 × Weight (kg) + 1.141 × Cr/CysC. The modified equation (Equation 2) with anthropometric data and HGS was as follows: ASM (kg) = -4.468 - 0.050 × Age (years) - 2.285 × Woman+ 0.079 × Height (cm) + 0.228 × Weight (kg) - 0.127 × Mid-arm muscular circumference (cm) + 1.127 × Cr/CysC. Both equations exhibited strong correlations with the ASM measured via BCM in the validation cohort (r = 0.944 and 0.943 for Equations 1 and 2, respectively) with minimal bias. When Equation 1 was applied to the CKD registry, the estimated ASM index (ASM/Height2) significantly predicted overall mortality over a median of 54 months. CONCLUSIONS: Novel ASM equations offer a simple method for predicting skeletal muscle mass and can provide valuable prognostic information regarding patients with nondialysis CKD.

Resistin: A Potential Indicator of Aortic Stiffness in Non-Dialysis Chronic Kidney Disease Patients.

Background and Objectives: In the progression and development of atherosclerosis, resistin plays a significant role. Chronic kidney disease (CKD), frequently associated with atherosclerosis, exhibits a marked increase in morbidity and mortality rates. This study set out to explore the association between aortic stiffness and serum levels of resistin in non-dialysis-dependent CKD patients ranging from stages 3 to 5. Materials and Methods: We collected fasting blood samples from 240 CKD patients across stages 3 to 5. The concentration of resistin in serum was determined using a commercially available enzyme immunoassay kit. Those patients who exhibited a carotid-femoral pulse wave velocity (cfPWV) greater than 10 m/s were identified as the aortic stiffness group. Results: Out of the 240 CKD patients, 88 (36.7%) were classified within the aortic stiffness group. This group demonstrated higher incidences of diabetes, advanced age, increased body weight, body mass index, body fat mass, systolic and diastolic blood pressure, fasting glucose, and serum resistin levels. Multivariate logistic regression analysis highlighted resistin, diabetes, and body weight as independent predictors of aortic stiffness. Additionally, body fat mass, logarithmically transformed cfPWV (log-cfPWV) values and log-triglyceride levels were independent predictors of log-resistin levels by multivariate stepwise linear regression analysis. Conclusions: In CKD patients from stages 3 to 5, a positive correlation exists between elevated serum resistin levels and cfPWV values, identifying resistin as a potential predictor of aortic stiffness.

Serum Angiopoietin-like Protein 3 Levels Are Associated with Endothelial Function in Patients with Maintenance Hemodialysis.

Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 (p < 0.001) and alkaline phosphatase (ALP, p = 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP, r = -0.187, p = 0.045) and log-ANGPTL3 (r = -0.319, p < 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI (p < 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI.

Serum Trimethylamine N-Oxide Levels Correlate with Metabolic Syndrome in Coronary Artery Disease Patients.

Trimethylamine N-oxide (TMAO) is a gut microbial metabolite that affects atherogenesis and glucose dysregulation. The purpose of this study was to look at the link between blood TMAO levels and metabolic syndrome (MetS) in individuals with coronary artery disease (CAD). Blood samples were obtained in fasting status, and serum TMAO level was quantified by high-performance liquid chromatography-mass spectrometry. MetS and its components were defined according to the International Diabetes Federation diagnostic criteria. Of 92 enrolled patients, 51 (55.4%) had MetS. Patients with MetS had a greater proportion of hypertension and diabetes mellitus, higher body weight, waist circumference, body mass index, systolic blood pressure, fasting glucose, triglycerides, blood urea nitrogen, creatinine, C-reactive protein (CRP), insulin level, homeostasis model assessment of insulin resistance, and TMAO level. Multivariable logistic regression models revealed that TMAO level (odds ratio: 1.036, 95% confidence interval: 1.005-1.067, p = 0.023) could be an effective predictor of MetS among the CAD population. In these patients, the log-TMAO level was positively associated with log-CRP (ß = 0.274, p = 0.001) and negatively associated with eGFR (ß = -0.235, p = 0.022). In conclusion, our study revealed a positive association between serum TMAO level and MetS among patients with CAD.

Low serum 3-methyl histidine level is associated with aortic stiffness in maintenance hemodialysis patients.

3-Methylhistidine (3MH) is an indicator of muscle catabolism. Subclinical protein malnutrition is an independent predictor of aortic stiffness (AS). We aimed to study the relationship between serum 3MH level and AS among patients undergoing maintenance hemodialysis (MHD). Carotid-femoral pulse wave velocity was applied to measure AS of 110 MHD patients. Serum 3MH levels were analyzed using high-performance liquid chromatography and mass spectrometry. AS was defined as cfPWV >10 m/s. Forty-five (40.9%) patients were categorized as having AS. Multivariable logistic (odds ratio: 0.792, p < 0.001) and linear (ß = -0.322, p < 0.001) regression analysis revealed that serum 3MH is an independent factor associated with AS among MHD patients. The diagnostic power of 3MH for AS in patients undergoing MHD was 0.691 (95% CI: 0.595-0.775, p = 0.0002). Low serum 3MH levels could be a potential biomarker related to AS among MHD patients.

Serum indices based on creatinine and cystatin C predict mortality in patients with non-dialysis chronic kidney disease.

Serum indices based on creatinine and cystatin C, including creatinine/cystatin C ratio (Cr/CysC), ratio and difference of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcys/eGFRcre and eGFRDiff), and serum creatinine × eGFRcys, are recently identified serum markers for sarcopenia. We aimed to evaluate the association between these serum indices and mortality in patients with chronic kidney disease (CKD). A single-center retrospective cohort study included 1141 adult patients with stage 1-5 CKD between 2016 and 2018. Basic characteristics, comorbidities, laboratory parameters, and serum creatinine and cystatin C values were obtained. Patients were followed up until death, dialysis, transfer to another hospital, or end of the study. The median age (interquartile range) of our participants was 71 (62-81) years. During a median follow-up of 39 months, 116 (10.2%) patients died. Compared to the survivor group, Cr/CysC, eGFRcys/eGFRcre, eGFRDiff, and Cr × eGFRcys were all lower in the non-survivors (p < 0.001 for all). The receiver operating characteristic curves of serum indices for predicting mortality showed that all four indices had significant discriminative power. Based on the Cox proportional hazard models, lower values of four serum indices, both as continuous and categorical variables, independently predicted mortality. Our findings suggest that low serum indices of Cr/CysC, eGFRcys/eGFRcre, eGFRDiff, and Cr × eGFRcys are independent indicators of mortality in patients with non-dialysis CKD.

Positive Associations between Adipocyte Fatty Acid-Binding Protein Level and Central Arterial Stiffness in Peritoneal Dialysis Patients.

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) plays essential roles in lipolysis, insulin resistance, and atherosclerosis. This study aimed to evaluate the relationship between serum A-FABP levels and carotid-femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients. METHODS: This study obtained fasting blood samples from 76 PD patients. A validated tonometry system was used to measure cfPWV. Patients with cfPWV values >10 m/s were classified into the high arterial stiffness group, whereas patients with values ≤10 m/s were classified into the low arterial stiffness group, according to the ESH-ESC 2013 guidelines. Serum A-FABP levels were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Twenty-five (32.9%) of the 76 PD patients were classified in the high arterial stiffness group. Compared with the patients in the low arterial stiffness group, the high arterial stiffness group was older (P = 0.002) and had a longer PD vintage (P = 0.011), higher diastolic blood pressure (DBP, P = 0.036), higher fasting glucose levels (P = 0.012), higher serum C reactive protein levels (P = 0.001), and higher serum A-FABP levels (P < 0.001). A multivariate logistic regression analysis of the factors significantly associated with central arterial stiffness revealed that A-FABP (odds ratio (OR): 1.165, 95% confidence interval (CI): 1.056-1.284, P = 0.002), age (OR: 1.423, 95% CI: 1.153-1.757, P = 0.001), PD vintage (OR: 1.049, 95% CI: 1.015-1.085, P = 0.005), and DBP (OR: 1.152, 95% CI: 1.033-1.285, P = 0.011) were independent predictors of central arterial stiffness in PD patients. Furthermore, serum A-FABP levels (ß = 0.476, adjusted R 2 change: 0.197, P < 0.001) were significantly positively correlated with cfPWV according to the multivariable forward stepwise linear regression analysis. CONCLUSIONS: A-FABP levels are an independent marker of central arterial stiffness in PD patients.

Serum Irisin Level Is Positively Associated with Bone Mineral Density in Patients on Maintenance Hemodialysis.

BACKGROUND: Irisin is a circulating hormone-like myokine that plays an important role in bone metabolism. We performed a cross-sectional study to investigate whether serum irisin levels correlated with bone mineral density (BMD) in patients on maintenance hemodialysis (MHD). METHODS: Blood samples were obtained from 80 patients on MHD, and serum irisin concentrations were determined using a commercially available enzyme-linked immunosorbent assay. BMD was measured by dual-energy X-ray absorptiometry of the L2-L4 vertebrae. RESULTS: In the study cohort, 10 (12.5%) and 19 (23.8%) patients had osteoporosis and osteopenia, respectively, and 51 (63.75%) patients had normal BMD. Lumbar T-score was negatively associated with body height (P=0.010), body weight (P=0.002), body mass index (BMI, P=0.010), and serum irisin (P < 0.001) and was positively associated with advanced age (P=0.031), female sex (P=0.001), alkaline phosphatase (ALP, P=0.010), urea reduction rate (P=0.018), and fractional clearance index for urea (P=0.020). Multivariable forward stepwise linear regression analysis revealed that high serum logarithmically transformed irisin (log-irisin, ß = 0.450, adjusted R 2 change = 0.258; P < 0.001), female sex (ß = -0.353, adjusted R 2 change = 0.134; P < 0.001), and serum ALP level (ß = -0.176, adjusted R 2 change = 0.022; P=0.049) were significantly and independently associated with lumbar BMD in patients on MHD. CONCLUSIONS: In addition to female sex and serum ALP level, serum irisin level was positively associated with lumbar BMD in patients on MHD.

Elevated serum leptin levels are associated with low muscle strength and muscle quality in male patients undergoing chronic hemodialysis.

OBJECTIVES: Low muscle strength and poor muscle quality are highly prevalent in patients with chronic hemodialysis (HD), which lead to an increased risk of poor clinical outcomes. Leptin dysregulation is common in HD patients. Given that leptin receptors are abundant in skeletal muscle, there may be a link between leptin and muscle strength. The cross-sectional study aimed to explore the correlation of serum leptin levels with muscle strength and muscle quality in patients with chronic HD. MATERIALS AND METHODS: A total of 118 chronic HD patients were included in this study. Basic characteristics, handgrip strength, body composition were assessed, and blood samples for serum leptin levels and other biochemical test were obtained. We defined skeletal muscle index (SMI) as skeletal muscle mass/height2 (kg/m2) and muscle quality as handgrip strength divided by mid-arm muscle circumference (MAMC). Patients were classified into tertile groups, according to sex-specific leptin levels. RESULTS: We observed that patients in the higher leptin tertile tend to have a higher body weight, body mass index (BMI), body fat mass, MAMC, and SMI, while the handgrip strength and muscle quality were significantly lower. Bodyweight (r = 0.30; P = 0.001), BMI (r = 0.45; P = 0.001), body fat mass (r = 0.57;P < 0.001), and SMI (r = 0.22; P = 0.018) were positively and handgrip strength (r = -0.27; P = 0.003) and muscle quality (r = -0.35;P < 0.001) were negatively correlated with serum leptin levels, respectively. After adjusting multiple confounding factors, logarithmically transformed serum leptin levels were independently associated with handgrip strength (ß = -3.29, P = 0.005) and muscle quality (ß = -0.14, P = 0.009). However, gender-stratified models showed the associations were observed only in male, but not in female. CONCLUSION: We concluded that higher serum leptin levels are associated with low handgrip strength and poor muscle quality in male patients on chronic HD. Further studies are needed to clarify the gender differences and to evaluate the casual relationship between circulating leptin levels and muscle strength.

Association of SARC-F Questionnaire and Mortality in Prevalent Hemodialysis Patients.

Sarcopenia is common in patients undergoing chronic hemodialysis, which leads to poor outcomes. SARC-F (sluggishness, assistance in walking, rising from a chair, climb stairs, falls), a self-report questionnaire, is recommended as an easily applied tool for screening sarcopenia in older people. However, there are limited data regarding its use in patients undergoing chronic hemodialysis. Therefore, we aimed to evaluate the association between SARC-F and mortality in these patients. SARC-F questionnaire was applied in 271 hemodialysis patients (mean age 64.4 ± 14.3 years) at baseline. The association between SARC-F and mortality during a 24-month follow-up was analyzed. During this follow-up period, 40 patients (14.8%) died. The discriminative power of SARC-F score for predicting mortality was 0.716 (95% confidence interval (CI) = 0.659-0.769; p < 0.001). The best cut-off was a score ≥ 1, which provided 85.0% sensitivity, 47.2% specificity, 21.8% positive predictive value, and 94.8% negative predictive value. Kaplan-Meier curves showed that patients with SARC-F ≥ 1 exhibited a higher risk of mortality than those with SARC-F < 1 (p < 0.001). Moreover, a stepwise decline in survival with higher SARC-F scores was also observed. After full adjustments, SARC-F ≥ 1 was independently associated with increased mortality (hazard ratio = 2.87, 95% CI = 1.11-7.38; p = 0.029). In conclusion, SARC-F applied for sarcopenia screening predicted mortality in patients undergoing chronic hemodialysis.

Association of Low Serum l-Carnitine Levels with Aortic Stiffness in Patients with Non-Dialysis Chronic Kidney Disease.

l-carnitine (LC) is a co-factor in fatty acid metabolism; its role with respect to aortic stiffness (AS) associated with chronic kidney disease (CKD) was unclear. Our aim was to investigate associations between serum LC levels and AS in patients with non-dialysis CKD stage 3-5. The AS patients were those with carotid-femoral pulse wave velocities (cfPWV) >10 m/s; those with cfPWV ≤10 m/s were included as controls. Serum LC was measured by liquid chromatography and mass spectrometry. Of 136 CKD patients, the 44 (32.4%) with AS were older, exhibited higher rates of diabetes, and had elevated diastolic and systolic blood pressures (SBP), elevated fasting glucose levels and lower levels of serum LC compared to controls. Multivariable logistic regression revealed that serum LC (odds ratio [OR] = 0.949, 95% confidence interval [CI] 0.911-0.988, p = 0.011) and age (OR = 1.055, 95% CI 1.013-1.099, p = 0.009) were independent predictors of AS. Multivariable stepwise linear regression revealed significant positive (age and SBP) and negative (serum LC) correlations with cfPWV. The area under the curve of serum LC as a means to predict AS in CKD patients was 0.657 (95% CI 0.571-0.736, p = 0.0009). We concluded that low serum LC is a significant predictor of AS in patients diagnosed with CKD.

Association of Serum Indoxyl Sulfate Levels with Skeletal Muscle Mass and Strength in Chronic Hemodialysis Patients: A 2-year Longitudinal Analysis.

Sarcopenia is highly prevalent in patients undergoing chronic hemodialysis (HD). This study investigated the relationship among serum indoxyl sulfate (IS) levels, muscle mass, and strength in HD patients. A total of 108 HD patients were enrolled. Skeletal muscle mass and handgrip strength (HGS) were assessed, using bioimpedance analysis and a hand-held dynamometer, respectively. Skeletal muscle index (SMI) was defined as skeletal muscle mass/height2 (kg/m2). Serum IS, p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO) levels were determined using liquid chromatography-mass spectrometry. Patients were classified into two groups based on median serum IS values. HGS measurement was repeated after 2 years. Patients in the high IS group had longer HD duration and higher serum TMAO levels than those in the low IS group. Log-normalized IS level was negatively correlated with SMI (r = - 0.227; p = 0.018), but PCS and TMAO levels were not. Among 78 patients who completed 2-year follow-up, those in the high IS group (n = 41) showed greater absolute (- 2.48 kg versus - 0.25 kg, p = 0.035) and relative HGS loss (- 9.1% versus 1.4%, p = 0.036) than those in the low IS group, after adjustment for potential confounders. Indoxyl sulfate (IS) may play a significant role in uremic sarcopenia. Further large-scale studies are needed to confirm our preliminary findings.

Serum Malondialdehyde-Modified Low-Density Lipoprotein Is a Risk Factor for Central Arterial Stiffness in Maintenance Hemodialysis Patients.

Circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) acts as a marker of oxidative stress and is associated with atherosclerotic cardiovascular disease. The relationship between serum MDA-LDL levels and aortic stiffness (AS) in patients with hemodialysis (HD) was evaluated. There were 155 HD patients enrolled in this study. Carotid-femoral pulse wave velocity (cfPWV) was measured by a validated tonometry system. Patients with cfPWV >10 m/s were used to define the AS group, while those with values of ≤10 m/s were regarded as the control group. Serum MDA-LDL levels were measured using a commercial enzyme-linked immunosorbent assay. Sixty-eight patients (43.9%) who were defined as AS sufferers, and were older, had a higher percentage of diabetes and hypertension and higher systolic blood pressure and serum MDA-LDL level compared to subjects in the control group. After adjusting for factors significantly associated with AS by multivariable logistic regression analysis, it was revealed that serum MDA-LDL levels, diabetes, and hypertension were independent predictors of AS in HD patients. Multivariable forward stepwise linear regression analysis also showed that a logarithmically transformed MDA-LDL level was significantly correlated with cfPWV values in HD patients. In HD patients, a high serum MDA-LDL level was positively associated with cfPWV values and was a significant predictor of the development of high AS.

Increased Serum Leptin Level Predicts Bone Mineral Density in Hemodialysis Patients.

BACKGROUND: Leptin acts through the adipose-bone axis to regulate bone mineral density (BMD). This study evaluated the relationship between BMD and serum leptin levels in patients on hemodialysis. METHODS: In this cross-sectional study including 98 hemodialysis patients, BMD was measured using dual energy X-ray absorptiometry of the lumbar vertebrae (L2-L4), and serum leptin levels were determined using an enzyme immunoassay. RESULTS: There were 25 (25.5%), 13 (13.3%), and 60 (61.2%) patients with osteopenia, osteoporosis, and normal BMD, respectively. Advanced age (P=0.017); decreased body mass index (BMI, P < 0.001); body height (P < 0.001); prehemodialysis body weight (BW, P < 0.001); post-hemodialysis BW (P < 0.001); waist circumference (P < 0.001); and triglyceride (P=0.015), albumin (P=0.004), and leptin levels (P=0.017) were associated with lower lumbar T scores, whereas increased urea reduction rate (URR, P=0.004) and fractional clearance index for urea (Kt/V, P=0.004) were associated with lower lumbar T scores. The multivariable forward stepwise linear regression analysis with adjustment for sex; age; body height; prehemodialysis BW; BMI; waist circumference; logarithmically transformed triglycerides (log-triglycerides), albumin, creatinine, and leptin (log-leptin) levels; URR; and Kt/V indicated that high serum level of log-leptin (R 2 change = 0.184; P < 0.001), increased prehemodialysis BW (R 2 change = 0.325; P=0.008), male sex (R 2 change = 0.048; P=0.001), young age (R 2 change = 0.044; P=0.012), and increased serum albumin level (R 2 change = 0.017; P=0.044) were significantly and independently associated with lumbar BMD. CONCLUSIONS: Advanced age and female sex were associated with poor BMD, whereas increased BW, serum albumin, and leptin levels were positively associated with BMD in patients on hemodialysis.

Lower Serum Fibroblast Growth Factor 21 Levels are Associated with Normal Lumbar Spine Bone Mineral Density in Hemodialysis Patients.

Recent evidence has indicated that fibroblast growth factor 21 (FGF21) regulates longitudinal bone growth, with increased FGF21 levels leading to bone loss. The present study evaluated the relationship between bone mineral density (BMD) and serum FGF21 levels in patients undergoing hemodialysis (HD). We analyzed blood samples from 95 patients undergoing HD and measured BMD using dual-energy X-ray absorptiometry of the lumbar vertebrae (L2-L4). Serum FGF21 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit. Thirteen (11.6%) patients were found to have osteoporosis, 27 (28.4%) osteopenia, and 57 patients had normal BMD. Advanced age and decreased body mass index, height, body weight, waist circumference, and triglyceride level were associated with lower lumbar T-scores, as were increased alkaline phosphatase, urea reduction rate, fractional clearance index for urea, and FGF21 levels. Low log-FGF21, increased body mass index, increased pre-HD body weight, and increased logarithmically transformed triglycerides (log-TG) were found to be significantly and independently associated with lumbar BMD by multivariate forward stepwise linear regression analysis with adjustment for significant confounders. We conclude that high serum FGF21 level is negatively associated with BMD in patients undergoing HD.

Negative correlation of serum adiponectin level with peripheral artery occlusive disease in hemodialysis patients.

OBJECTIVE: Adiponectin is a fat-derived hormone that secretes exclusively by adipocytes and has antiatherosclerotic effects. Peripheral arterial occlusive disease (PAOD) is associated with an increased risk of death in hemodialysis (HD) patients. The aim of this study was to evaluate the relationship between serum adiponectin levels and PAOD by ankle-brachial index (ABI) in HD patients. MATERIALS AND METHODS: Blood samples were obtained from 100 HD patients. Serum adiponectin levels were measured using a commercial enzyme-linked immunosorbent assay kit. ABI values were measured using the automated oscillometric method (VaSera VS-1000). ABI values that <0.9 were included in the low ABI group. RESULTS: Among the 100 HD patients, 18 of them (18.0%) were in the low ABI group. Compared with patients in the normal ABI group, the patients in the low ABI group had a higher prevalence of diabetes (P = 0.043), older age (P = 0.027), and lower serum adiponectin level (P = 0.003). In addition, the multivariable logistic regression analysis showed that adiponectin (Odds ratio [OR]: 0.927, 95% confidence interval [CI]: 0.867-0.990, P = 0.025) and age (OR: 1.054, 95% CI: 1.002-1.109, P = 0.043) were the independently associated with PAOD in HD patients. CONCLUSION: In this study, serum adiponectin level was found to be associated with PAOD in HD patients.

Serum Sclerostin But Not DKK-1 Correlated with Central Arterial Stiffness in End Stage Renal Disease Patients.

Sclerostin and dickkopf-1 (DKK1) played a role in the development of cardiovascular diseases and arterial stiffness in chronic kidney disease (CKD) patients but with controversial results of patients in end-stage renal disease (ESRD) including hemodialysis (HD) and peritoneal dialysis (PD). This study aimed to examine the association between the mode of dialysis or the values of sclerostin or DKK1 and carotid-femoral pulse wave velocity (cfPWV) in ESRD patients. There were 122 HD and 72 PD patients enrolled in this study. By a validated tonometry system, cfPWV was measured and then segregated patients into values of >10 m/s as the high central arterial stiffness (AS) group and values ≤ 10 m/s as the control group. Serum levels of sclerostin and DKK1 were measured using a commercial enzyme-linked immunosorbent assay kit. Possible risk factors for the development of AS were analyzed by logistic regression analysis. There were 21 (29.2%) of PD and 53 (43.4%) of HD in the high AS group. Compared to patients in the control group, those in the high AS group were older, had more comorbidities, had higher systolic blood pressure, and had higher serum levels of fasting glucose, C-reactive protein, and sclerostin. Levels of sclerostin (adjusted OR 1.012, 95% CI. 1.006-1.017, p = 0.0001) was found to be an independent predictor of high AS in ESRD patients by multivariate logistic regression analysis. Furthermore, receiver operating characteristic curve analysis showed the optimal cut-off values of sclerostin for predicting AS was 208.64 pmol/L (Area under the curve 0.673, 95% CI: 0.603-0.739, p < 0.001). This study showed that serum levels of sclerostin, but not DKK1 or mode of dialysis, to be a predictor for high central AS in ESRD patients.

Serum osteoprotegerin level is positively associated with peripheral artery disease in patients with peritoneal dialysis.

Osteoprotegerin (OPG) is a potential biomarker of cardiovascular disease complications and severity. Peripheral arterial disease (PAD) is associated with an increased risk of death in patients on peritoneal dialysis (PD). Therefore, this study aimed to evaluate the relationship between serum OPG levels and PAD by measuring the ankle-brachial index (ABI) of patients on PD. A commercial enzyme-linked immunosorbent assay kit was used to measure OPG values. Left or right ABI values of <0.9 were categorized as the low ABI group. Among 70 patients on PD, 13 (18.6%) were categorized in the low ABI group. Patients in the low ABI group had higher prevalence of diabetes mellitus (p = .044) and higher serum C-reactive protein (CRP) (p < .001) and OPG levels (p < .001) but lower creatinine (p = .013) and peritoneal Kt/V (p = .048) levels than those in the normal ABI group. Results of multivariable logistic regression analysis revealed that OPG [adjusted odds ratio (aOR) 1.027, 95% confidence interval (CI) 1.010-1.045, p = .002] and CRP (aOR 1.102, 95% CI 1.006-1.207, p = .037) levels were independent predictors of PAD in patients on PD. OPG can also be used to predict PAD development with the area under the receiver operating characteristic curve of 0.823 (95% CI: 0.714-0.904, p < .001) in patients on PD. Therefore, serum OPG and CRP levels can be considered as risk factors for PAD development in patients on PD.