High Serum Galectin-3 Level as a Potential Biomarker of Peripheral Artery Disease in Patients Undergoing Hemodialysis.

Background: Galectin-3 is implicated in the pathogenesis of inflammation and atherosclerosis. Peripheral arterial disease (PAD), characterized by a reduced ankle-brachial index (ABI), is a prognostic marker for mortality in patients on hemodialysis. We investigated the relationship between serum galectin-3 levels and PAD in patients undergoing regular hemodialysis. Methods: We carried out a cross-sectional study at a medical center, involving 92 participants. Serum galectin-3 levels were assessed by a commercially available enzyme-linked immunosorbent assay. ABI measurement was done with an automatic device based on oscillometry. Participants were categorized into two groups, normal and low ABI, based on a 0.9 cut-off point. Results: Eighteen patients (19.6%) exhibited a low ABI. In individuals with low ABIs, we observed a greater prevalence of diabetes mellitus, elevated serum C-reactive protein (CRP) levels, increased galectin-3 levels, and lower serum creatinine levels. Furthermore, serum galectin-3 levels (odds ratio [OR]: 1.056, 95% confidence interval [CI]: 1.003-1.112, p = 0.037) and CRP (per 0.1 mg/dL increment, OR: 1.195, 95% CI: 1.032-1.383, p = 0.017) were identified as independent predictors of PAD. Serum galectin-3 and log-transformed CRP levels were also independently and significantly negatively correlated with the left and right ABI values. Conclusions: Serum galectin-3 levels correlate with PAD in patients undergoing maintenance hemodialysis.

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 Osteocalcin Level is Negatively Associated with Vascular Reactivity Index by Digital Thermal Monitoring in Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Osteocalcin is the most abundant noncollagenous protein in bone matrix, which is considered a marker of bone formation. Previous studies indicate that circulating osteocalcin can be expressed by osteoblasts and even by osteoblast-like cells in vessel walls, and it is often associated with arterial stiffness. Our study aims to examine the potential association between osteocalcin levels and endothelial function among kidney transplant (KT) recipients. MATERIALS AND METHODS: Fasting blood samples were obtained from 68 KT recipients. To measure the endothelial function and vascular reactivity index (VRI), a digital thermal monitoring test (VENDYS) was used. A commercial enzyme-linked immunosorbent assay kit was also utilized to measure serum total osteocalcin levels. In this study, a VRI of less than 1.0 indicated poor vascular reactivity; a VRI of 1.0-2.0 indicated intermediate vascular reactivity; and a VRI of 2.0 or higher indicated good vascular reactivity. RESULTS: Our findings show that 8 KT recipients (11.8%) had poor vascular reactivity (VRI < 1.0), 26 (38.2%) had intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 34 (50%) had good vascular reactivity. Increased serum osteocalcin levels (p < 0.001) were found to be associated with poor vascular reactivity. Advanced age (r = -0.361, p = 0.002), serum alkaline phosphate level (r = -0.254, p = 0.037), and log-transformed osteocalcin levels (r = - 0.432, p < 0.001) were identified to be negatively correlated with VRI in KT recipients. Multivariable forward stepwise linear regression analysis revealed that the serum level of osteocalcin (ß = -0.391, adjusted R2 change = 0.174; p < 0.001) and advanced age (ß = -0.308, adjusted R2 change = 0.084; p = 0.005) were significantly and independently associated with VRI in KT recipients. CONCLUSIONS: Higher serum osteocalcin level was associated with lower VRI and poorer endothelial dysfunction among KT recipients.

Electrochemical Skin Conductance by Sudoscan in Non-Dialysis Chronic Kidney Disease Patients.

BACKGROUND: Peripheral neuropathy is prevalent among patients with chronic kidney disease (CKD). Sudoscan non-invasively detects polyneuropathy by measuring electrochemical skin conductance (ESC). We conducted a study on sudomotor function in CKD patients across various stages based on their estimated glomerular filtration rate (eGFR). METHODS: In this cross-sectional study of 700 CKD patients, all underwent Sudoscan. Pathological ESC was defined as hands < 40 µS or feet < 50 µS. Clinical neuropathy scores including Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique en 4 questionnaire (DN4) were obtained. RESULTS: Among participants, 344 had diabetes and 356 did not. Hands and feet ESC decreased with CKD progression (median (IQR) in stage 1-2, 3, 4-5: 54.0 (39.0-68.0), 45.5 (30.0-63.0), 41.8 (26.5-60.5), p trend < 0.001; 64.5 (53.5-74.0), 60.5 (43.0-72.5), 55.0 (39.0-69.8), p trend < 0.001). Pathological hands and feet ESC increased in later CKD stages (stage 1-2, 3, 4-5: 26.6%, 40.9%, 45.7%, p trend < 0.001; 21.7%, 34.0%, 40.6%, p trend < 0.001). Positive hands and feet ESC-eGFR correlation existed irrespective of diabetes. Diabetic patients had lower hands and feet ESC than non-diabetics as CKD progressed. However, multivariate regression found no significant ESC-eGFR association. Sudoscan correlated with clinical neuropathy scores. CONCLUSION: Pathological sudomotor function was common in non-dialysis CKD stages 4-5. Diabetic patients had worse function. Sudomotor dysfunction progressed with renal disease but eGFR was not an independent risk factor.

Serum Fibroblast Growth Factor 21 Level Is Associated with Aortic Stiffness in Patients on Maintenance Hemodialysis.

BACKGROUND: Fibroblast growth factor 21 (FGF-21) is a hormone that regulates glucose and lipid metabolism. High serum FGF-21 levels are associated with carotid atherosclerosis and coronary artery disease. This cross-sectional study aimed to assess the relationship between serum FGF-21 levels and carotid-femoral pulse wave velocity (cfPWV) in patients on maintenance hemodialysis (HD). METHODS: Blood samples and baseline characteristics were collected from 130 HD patients. Serum FGF-21 concentrations were measured with an enzyme-linked immunosorbent assay kit. Aortic stiffness was defined as a carotid-femoral pulse wave velocity (cfPWV) of more than 10 m/s. RESULTS: Of the 130 HD patients, aortic stiffness was diagnosed in 54 (41.5%). Serum FGF-21 levels were significantly higher in those with aortic stiffness than those without (P < 0.001). The FGF-21 level was independently associated with aortic stiffness (odds ratio (OR): 1.008; 95% CI: 1.003-1.012; P=0.001) after adjusting for diabetes mellitus, age, hypertension, C-reactive protein, and body weight in multivariable logistic regression analysis. Multivariable forward stepwise linear regression analysis also confirmed that the logarithmically transformed FGF-21 level (ß = 3.245, 95% CI: 1.593-4.987, P < 0.001) was an independent predictor of cfPWV values. The area under the receiver operating characteristic (ROC) curve predicting aortic stiffness by the serum FGF-21 level was 0.693 (95% CI: 0.606-0.771, P < 0.001). CONCLUSIONS: Serum FGF-21 level positively correlates with cfPWV and is also an independent predictor of aortic stiffness in maintenance HD patients.

The serum sclerostin level is positively associated with the aortic augmentation index in patients on peritoneal dialysis.

OBJECTIVE: Sclerostin is a canonical Wingless (Wnt)/ß-catenin signaling pathway inhibitor and had been associated with high arterial stiffness in patients with chronic kidney disease. The aortic augmentation index (AIx), a noninvasive method of assessing central hemodynamics/wave reflections, has been widely used as a clinical index of arterial stiffness. The aim of this study was to evaluate the relationship between fasting serum sclerostin levels and AIx values in peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Fasting blood samples were obtained from 75 PD patients. The aortic AIx value was measured using a validated tonometry system (SphygmoCor, AtCor Medical, Sydney, New South Wales, Australia). Serum sclerostin and dickkopf-1 (DKK1) levels were quantified using commercial enzyme-linked immunosorbent assay kits. RESULTS: Women PD patients had higher aortic AIx values than men (P = 0.039), while lower aortic AIx values were found in PD patients who used statins (P = 0.004). Univariate linear analysis of the aortic AIx values in PD patients showed that systolic blood pressure (P = 0.001), diastolic blood pressure (P = 0.018), and serum sclerostin levels (P = 0.001) were positively correlated, while height (P = 0.018), body weight (P = 0.001), body mass index (P = 0.043), and weekly total creatinine clearance (P = 0.015) were negatively correlated with aortic AIx values in PD patients. Multivariate linear regression analysis of the factors significantly associated with the aortic AIx values showed that serum sclerostin levels (adjusted R 2 = 0.057, P = 0.011) and systolic blood pressure (adjusted R 2 = 0.125, P = 0.004) were positively associated, while body weight (adjusted R 2 = 0.113, P = 0.002) was inversely associated with aortic AIx values in PD patients. CONCLUSION: In this study, the serum sclerostin level, but not DKK1, was positively associated with aortic AIx values in PD patients.