Serum Lipoprotein(a) Levels as a Predictor of Aortic Stiffness in Patients on Long-Term Peritoneal Dialysis.

BACKGROUND Lipoprotein (a) [Lp(a)] is associated with atherosclerosis and cardiovascular mortality in patients with kidney failure. Aortic stiffness (AS), measured primarily by carotid-femoral pulse wave velocity (cfPWV), reflects vascular aging and precedes end-organ failure. This study aimed to evaluate the association between serum Lp(a) levels and cfPWV in patients undergoing peritoneal dialysis (PD). MATERIAL AND METHODS In this cross-sectional study, which included 148 patients with long-term PD for end-stage kidney failure, cfPWV was measured using a cuff-based method. AS was defined as a cfPWV exceeding 10 m/s, and an enzyme-linked immunosorbent assay was used to determine serum Lp(a) levels. Univariate and multivariate regression analyses were performed to identify the clinical correlates of AS. RESULTS There were 32 (21.6%) patients diagnosed with AS. Based on the multivariate logistic regression analysis, the odds ratio for AS was 1.007 (95% confidence interval, 1.003-1.011; P=0.001) for every 1 mg/L increase in Lp(a) levels. Multivariate linear regression analysis showed that Lp(a) (P<0.001), age (P=0.003), waist circumference (P=0.008), systolic blood pressure (P=0.010), and diabetes mellitus (P<0.001) were positively associated with cfPWV. The area under the receiver operating characteristic curve for Lp(a) in differentiating AS from non-AS was 0.770 (95% confidence interval, 0.694-0.835; P<0.0001). CONCLUSIONS Serum Lp(a) level was independently associated with cfPWV and AS in patients with PD.

Osteocalcin: A Potential Marker of Peripheral Arterial Stiffness in Hypertensive Patients.

Background and Objectives: Brachial-ankle pulse wave velocity (baPWV) is an established independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is recognized to be associated with vascular function. The present study assessed the correlation between serum OC levels and peripheral arterial stiffness (PAS) measured through baPWV in hypertensive patients. Materials and Methods: Fasting blood samples were collected from 120 hypertensive participants. The serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit, whereas the baPWV device was used to detect PAS. The PAS group had left or right baPWV > 18.0 m/s. Results: Among the hypertensive patients, 24 (20.0%) were classified into the PAS group. The PAS group exhibited a significantly older age (p = 0.011), higher prevalence of diabetes (p = 0.010), systolic blood pressure (p = 0.019), levels of serum fasting glucose (p = 0.003), blood urea nitrogen (p = 0.024), creatinine (p = 0.004), C-reactive protein (p = 0.007), OC (p = 0.002), and lower estimated glomerular filtration rate (p = 0.004) than the non-PAS group. Age (odds ratio [OR]: 1.076, 95% CI: 1.004-1.153, p = 0.037) and serum OC level (OR: 1.797, 95% confidence interval (CI): 1.077-3.000, p = 0.025) were independent factors linked to PAS in hypertensive patients in the multivariate logistic regression analysis. Conclusions: Serum OC levels and older age are positively associated with PAS in hypertensive patients.

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.

Empagliflozin Attenuates Vascular Calcification in Mice with Chronic Kidney Disease by Regulating the NFR2/HO-1 Anti-Inflammatory Pathway through AMPK Activation.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, such as empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1ß, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate-induced VC in mouse vascular smooth muscle cells (VSMCs) to investigate the mechanisms underlying empagliflozin's therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE-/- mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate-induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE-/- mice on a high-phosphate diet.

Associations of Glucometabolic Indices with Aortic Stiffness in Patients Undergoing Peritoneal Dialysis with and without Diabetes Mellitus.

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (ß = 0.52, 95% confidence interval [CI] = 0.01-1.03, p = 0.046), high HOMA-IR (ß = 0.60, 95% CI = 0.12-1.08, p = 0.015), and a high PD glucose load (ß = 0.58, 95% CI = 0.08-1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness.

Serum Osteoprotegerin Levels and the Vascular Reactivity Index in Patients with Hypertension.

Background and Objectives: Osteoprotegerin (OPG), a soluble glycoprotein found in serum, has been associated with both the presence and severity of atherosclerosis. OPG is regarded as the mediator in the process of vascular endothelial dysfunction. Impaired endothelial function has an intimate link with hypertension (HTN) and is associated with significant morbidity and mortality. This study was to investigate the connection between OPG and endothelial dysfunction in patients having HTN. Materials and Methods: There are 102 patients with HTN included. For the purpose of determining the levels of OPG, a commercial enzyme-linked immunosorbent test kit was applied. The vascular reactivity index (VRI), which is assessed via the digital thermal monitoring, provides information on endothelial function. Results: Ten patients with HTN (9.8%) were classified as having poor vascular reactivity (VRI < 1.0), 46 HTN patients (45.1%) as having intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 46 HTN patients (45.1%) were classified as having high vascular reactivity (VRI ≥ 2.0). A greater serum OPG level (p < 0.001) and older age (p = 0.022) were linked to impaired vascular reactivity. The estimated glomerular filtration rate (r = 0.196, p = 0.048) was positively correlated with VRI values in hypertensive participants, while advanced age (r = -0.222, p = 0.025) and the log-transformed OPG level (log-OPG, r = -0.357, p < 0.001) were negatively correlated with VRI. Serum log-OPG level was shown to be strongly and independently correlated with VRI values in HTN individuals after multivariable forward stepwise linear regression analysis (ß = -0.357, adjusted R2 change = 0.119, p < 0.001). Conclusions: In patients with HTN, serum OPG levels were adversely correlated with VRI and probably had a role in endothelial dysfunction.

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.

Dapagliflozin Ameliorates Lipopolysaccharide Related Acute Kidney Injury in Mice with Streptozotocin-induced Diabetes Mellitus.

Sepsis, which is a serious medical condition induced by infection, has been the most common cause of acute kidney injury (AKI) and is associated with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral antidiabetic drug that has greatly improved the cardiovascular and renal outcomes in patients with type 2 diabetes independent of its sugar lowering effect, possibly by attenuation of the inflammatory process. We investigated the effect of the SGLT2 inhibitor dapagliflozin on lipopolysaccharide (LPS)-induced endotoxic shock with AKI in streptozotocin-induced diabetic mice. Endotoxin shock with AKI was induced by intravenous injection of 10 mg/kg LPS in C57BL6 mice with streptozotocin-induced diabetic mellitus with or without dapagliflozin treatment. Observation was done for 48 hours thereafter. In addition, NRK-52E cells incubated with LPS or dapagliflozin were evaluated for the possible mechanism. Treatment with dapagliflozin attenuated LPS-induced endotoxic shock associated AKI and decreased the inflammatory cytokines in diabetic mice. In the in vitro study, dapagliflozin decreased the expression of inflammatory cytokines and reactive oxygen species and increased the expressions of AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor, and heme oxygenase 1. These results demonstrated that dapagliflozin can attenuate LPS-induced endotoxic shock associated with AKI; this was possibly mediated by activation of the AMPK pathway.

Hypoadiponectinemia is associated with aortic stiffness in nondialysis diabetic patients with stage 3-5 chronic kidney disease.

OBJECTIVES: Albuminuria and serum adiponectin levels are factors that have been associated with the development of cardiovascular disease in patients with diabetes mellitus. Here we investigated the relationship between serum adiponectin levels and aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. METHODS: Fasting blood samples were obtained from 80 nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. Carotid-femoral pulse wave velocity (cfPWV) was measured using applanation tonometry; cfPWV values of >10 m/s were defined as aortic stiffness. Serum adiponectin levels were determined by enzyme immunoassay. RESULTS: Forty-two patients (52.5%) with nondialysis diabetic kidney disease were diagnosed with aortic stiffness. The patients in this group were older (p = 0.011), had higher systolic blood pressure (p = 0.002) and urine albumin-to-creatinine ratios (p = 0.013), included fewer females (p = 0.024), and had lower serum adiponectin (p = 0.001) levels than those in the control group. Multivariable logistic regression analysis revealed that serum adiponectin was independently associated with aortic stiffness (odds ratio = 0.930, 95% confidence interval: 0.884-0.978, p = 0.005) and also positively correlated with cfPWV values by multivariable linear regression (ß = -0.309, p = 0.002) in nondialysis diabetic kidney disease patients. CONCLUSIONS: The results suggested that serum adiponectin levels could be used to predict aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease.

Positive correlation of serum indoxyl sulfate level with peripheral arterial disease in hemodialysis patients.

OBJECTIVES: Indoxyl sulfate, known for its cardiovascular toxicity, is associated with vascular and coronary artery diseases and increased mortality. Peripheral arterial disease, defined by low ankle-brachial index, is associated with increased mortality in patients on hemodialysis. The present study aimed to determine the relationship between the serum indoxyl sulfate level and peripheral arterial disease in patients on maintenance hemodialysis. METHODS: The present cross-sectional, single-center study included 75 patients on maintenance hemodialysis. Serum indoxyl sulfate levels were determined by high-performance liquid chromatography-mass spectrometry. Ankle-brachial index values were measured using an automated oscillometric device. Patients with ankle-brachial indexes of < 0.9 were categorized into the low ankle-brachial index group. RESULTS: In the study cohort, 12 of the 75 patients (16.0%) had low ankle-brachial indexes. The rates of diabetes mellitus (p = 0.010) as well as the serum levels of C-reactive protein (p < 0.001) and indoxyl sulfate (p < 0.001) were higher in the low ankle-brachial index group than the normal ankle-brachial index group. The multivariable logistic regression analysis revealed that serum levels of indoxyl sulfate (odds ratio = 1.123, 95% confidence interval 1.011-1.249, p = 0.031) and C-reactive protein (each 0.1 mg/dL increase, odds ratio = 1.169, 95% confidence interval 1.018-1.343, p = 0.027) were independently associated with peripheral arterial disease in patients on maintenance hemodialysis. CONCLUSIONS: Serum indoxyl sulfate levels were associated with peripheral arterial disease in patients on maintenance hemodialysis.

Association of serum fibroblast growth factor 21 levels with skeletal muscle mass and mortality in chronic hemodialysis patients.

BACKGROUND/PURPOSE: Fibroblast growth factor 21 (FGF21) is a hormone that modulates metabolic pathways, which acts as a myokine under metabolic stress. We aimed to explore the association of serum FGF21 levels with skeletal muscle mass and mortality in patients on hemodialysis (HD). METHODS: Baseline serum FGF21 levels were measured, and a portable whole-body bioelectrical impedance device was used to assess skeletal muscle mass. One hundred twenty-four patients undergoing chronic HD were categorized into high- and low-FGF21 groups according to the median FGF21 value. RESULTS: Patients with low FGF21 values had lower body weight, body mass index, skeletal muscle mass index (SMI = skeletal muscle mass/height2), and serum triglyceride levels. Log serum FGF21 levels revealed a modest but positive correlation with SMI (r = 0.30, p = 0.001) and independently predicted SMI after multiple adjustment (ß = 1.59, p = 0.027). During a median follow-up period of 66 months, all-cause mortality and cardiovascular death rates did not differ significantly between the high- and low-FGF21 groups. We also failed to demonstrate FGF21 as an independent predictor of all-cause mortality. CONCLUSION: Serum FGF21 levels exhibited a positive association with skeletal muscle mass but were not predictive of mortality in patients undergoing chronic HD.

Serum Sclerostin Level Is Negatively Associated with Bone Mineral Density in Hemodialysis Patients.

Background and Objectives: Sclerostin and Dickkopf-1 (DKK1) modulate osteoblastogenesis, but their role in bone loss in hemodialysis (HD) patients is inconclusive. This study investigated relationships among lumbar bone mineral density (BMD), serum sclerostin, and DKK1 in HD patients. Materials and Methods: Blood samples were obtained from 75 HD patients. Dual-energy X-ray absorptiometry measured lumbar BMD of the lumbar vertebrae (L2−L4). Enzyme-linked immunosorbent assay revealed serum sclerostin and DKK1 concentrations. Results: There were 10 (13.3%), 20 (26.7%), and 45 (60%) patients defined as presenting with osteoporosis, osteopenia, or normal BMD, respectively. Age, alkaline phosphatase, urea reduction rate, fractional clearance index for urea, sclerostin level, and percentage of female patients are significantly negatively associated with the lumbar BMD and T-score, while the body mass index and waist circumference significantly positively associated with the lumbar BMD and T-score. Multivariate forward stepwise linear regression analysis indicated that serum sclerostin (ß = −0.546, adjusted R2 change = 0.454; p < 0.001), age (ß = −0.216, adjusted R2 change = 0.041; p = 0.007), and percentage of female HD patients (ß = −0.288, adjusted R2 change = 0.072; p = 0.0018) were significantly negatively associated with lumbar BMD in HD patients. Conclusions: Advanced age, female gender, and serum sclerostin level, but not DKK1, were negatively associated with BMD in HD patients.

Discovery of Novel Protein Biomarkers in Urine for Diagnosis of Urothelial Cancer Using iTRAQ Proteomics.

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.

Association between serum indoxyl sulfate levels with carotid-femoral pulse wave velocity in patients with chronic kidney disease.

BACKGROUND: The role of indoxyl sulfate (IS), an important protein-bound uremic toxin, in arterial stiffness (AS) in patients with chronic kidney disease (CKD) is unclear. MATERIALS AND METHODS: We investigated the association between serum IS levels and AS in a cross-sectional study of 155 patients with CKD. Patients in the AS group was defined as carotid-femoral pulse wave velocity (cfPWV) value >10 m/s measured by a validated tonometry system (SphygmoCor), while values ≤10 m/s were regarded as without AS group Serum IS was measured by liquid chromatography-mass spectrometry analysis. RESULTS: Of these CKD patients, AS was present in 51 (32.9%) patients, who were older, had a higher rate of diabetes, higher systolic blood pressure (SBP), and higher IS levels compared to those without AS. By multivariable logistic regression analysis, IS (adjusted odds ratio [aOR] 1.436, 95% confidence interval [CI] 1.085-1.901, p = 0.011), age (aOR 1.058, 95% CI 1.021-1.097, p = 0.002), and SBP (aOR 1.019, 95%CI 1.000-1.038, p = 0.049) were independent predictors of AS. By multivariable stepwise linear regression analysis, logarithmically transformed IS, age, DM, and SBP were significantly correlated with cfPWV. The area under the receiver-operating characteristic curve for serum log-IS was 0.677 (95%CI 0.598-0.750, p = 0.0001) to predict the development of AS in patients with CKD. CONCLUSION: These finding demonstrate that in addition to older and higher SBP, a high serum IS level is a significant biomarker associated with AS in patients with CKD.

Linagliptin Protects against Endotoxin-Induced Acute Kidney Injury in Rats by Decreasing Inflammatory Cytokines and Reactive Oxygen Species.

Septic shock can increase pro-inflammatory cytokines, reactive oxygen species (ROS), and multiple organ dysfunction syndrome (MODs) and even lead to death. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been proven to exert potential antioxidant and anti-inflammatory effects. We investigated the effects of linagliptin on endotoxic shock and acute kidney injury (AKI) in animal and cell models. In the cell model, linagliptin attenuated ROS by activating the AMP-activated protein kinase (AMPK) pathway, restoring nuclear-factor-erythroid-2-related factor (Nrf2) and heme oxygenase 1 (HO-1) protein, and decreasing pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß)). In the animal model, 14-week-old conscious Wistar-Kyoto rats were randomly divided into three groups (n = 8 in each group). Endotoxin shock with MODs was induced by the intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 20 mg/kg). Linagliptin improved animal survival without affecting hemodynamic profiles. In the histopathology and immunohistochemistry examinations of the rat kidneys, linagliptin (10 mg/kg) suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide synthase (iNOS), decreased injury scores, and preserved E-cadherin expression from LPS damage. In conclusion, linagliptin ameliorated endotoxin-shock-induced AKI by reducing ROS via AMPK pathway activation and suppressing the release of TNF-α and IL-1ß in conscious rats.

Serum Angiopoietin-like Protein 3 Level Is Associated with Peripheral Arterial Stiffness in Patients with Coronary Artery Disease.

Background and Objectives: Angiopoietin-like protein 3 (ANGPTL3) is a secretory protein regulating lipid metabolism. This study evaluated the relationship between serum ANGPTL3 level and peripheral arterial stiffness (PAS) in patients with coronary artery disease (CAD). Materials and Methods: Fasting blood samples were collected from 95 CAD patients. PAS was defined as left or right brachial-ankle pulse wave velocity (baPWV) > 18.0 m/s by an oscillometric method. Serum ANGPTL3 levels were assessed using a commercial enzyme-linked immunosorbent assay kit. Results: Seventeen CAD patients (17.9%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.002), older age (p = 0.030), higher systolic blood pressure (p = 0.016), higher fasting glucose (p = 0.008), serum C-reactive protein (p = 0.002), and ANGPTL3 level (p = 0.001) than those without PAS. After multivariable logistic regression analysis, serum ANGPTL3 level (Odds ratio (OR): 1.004, 95% confidence interval (CI): 1.000-1.007, p = 0.041) is still independently associated with PAS in CAD patients. The receiver operating characteristic curve for PAS prediction revealed that the area under the curve for ANGPTL3 level was 0.757 (95% CI: 0.645-0.870, p < 0.001). Conclusions: Serum fasting ANGPTL3 level is positively associated with PAS in CAD patients. Further studies are required for clarification.

Serum Osteoprotegerin Level Is Negatively Associated with Bone Mineral Density in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Osteoprotegerin (OPG), a potent osteoclast activation inhibitor, decreases bone resorption and plays a role in mediating bone mineral density (BMD). Our aim was to evaluate the relationship between BMD and serum OPG in maintenance hemodialysis (MHD) patients. MATERIALS AND METHODS: Fasting blood samples were obtained from 75 MHD patients. BMD was measured by dual-energy X-ray absorptiometry in lumbar vertebrae (L2-L4). The WHO classification criteria were applied to define osteopenia and osteoporosis. A commercial enzyme-linked immunosorbent assay was used to measure serum OPG values. RESULTS: Among all MHD patients, seven (9.3%) and 20 patients (26.7%) were defined as osteoporosis and osteopenia, respectively. Female patients had lower lumbar BMD than males (p = 0.002). Older age (p = 0.023), increased serum OPG (p < 0.001) urea reduction rate (p = 0.021), Kt/V (p = 0.027), and decreased body mass index (p = 0.006) and triglycerides (p = 0.020) were significantly different between the normal, osteopenia, and osteoporosis groups. Lumbar spine BMD was positively correlated with body mass index (BMI) (p < 0.001) but negatively correlated with OPG (p < 0.001) and age (p = 0.003). After grouping patients into T scores < -1 and < -2.5, female sex and OPG (adjusted odds ratio [aOR] 1.022, 95% confidence interval [C.I.] 1.011-1.034, p < 0.001) were predictors of T scores < -1, whereas only OPG was predictive of T scores < -2.5 (aOR 1.015, 95% C.I. 1.005-1.026, p = 0.004) by multivariate stepwise logistic regression analysis. The areas under the curve for predicting T scores < -1 or < -2.5 were 0.920 (95% C.I. 0.834-0.970, p < 0.001) and 0.958 (95% C.I. 0.885-0.991, p < 0.001), respectively. CONCLUSIONS: Increased serum OPG negatively correlated with lumbar BMD and could be a potential biomarker predictive of osteoporosis in MHD patients.

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 indoxyl sulfate as a potential biomarker of aortic arterial stiffness in coronary artery disease.

BACKGROUND AND AIMS: Indoxyl sulfate (IS), a dietary tryptophan metabolite, acts as a cardiotoxin and uremic toxin. High IS levels are associated with chronic kidney disease and cardiovascular diseases. This study investigated the association between serum IS levels and aortic arterial stiffness (AAS) in coronary artery disease (CAD) patients. METHODS AND RESULTS: The carotid-femoral pulse wave velocity (cfPWV) was measured by the SphygmoCor system and patients with values of >10 m/s were classified in the AAS group. The baseline characteristics were recorded and measured (including biochemical and clinical data). Serum IS levels were determined using liquid chromatography-mass spectrometry. AAS occurred in 50 (34.7%) of 144 patients with CAD. They were older, had higher IS levels and percentages of diabetes, systolic blood pressure, blood urea nitrogen, and creatinine but lower estimated glomerular filtration rates. The IS level and older age significantly correlated with AAS [odds ratio (OR) = 3.834, p = 0.031; OR = 1.095, p = 0.002, respectively]. Furthermore, the serum IS level (ß = 0.167, adjusted R2 change: 0.026, p = 0.027) had a significant positive correlation with cfPWV. CONCLUSIONS: Taken together, higher serum IS levels are potential independent biomarkers for AAS in patients with CAD. Therefore, early checking of serum IS levels may help prevent CAD progression and have clinical implications in the near future.

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.