Serum myostatin level is a positive predictor of endothelial function measured by digital thermal monitoring of vascular reactivity in kidney transplantation patients.

OBJECTIVES: Myostatin is a myokine predominantly expressed and secreted in skeletal muscle in response to stimulations, including oxidative stress or inflammation. We investigated a potential association between myostatin levels and endothelial function among kidney transplantation (KT) patients. MATERIALS AND METHODS: Fasting blood samples were collected from 64 KT patients. The endothelial function that indicated by vascular reactivity index (VRI) was measured by digital thermal monitoring test. Serum myostatin levels were measured using a commercial enzyme-linked immunosorbent assay kit. All patients were categorized into three groups according to their VRI values: poor vascular reactivity was considered if VRI <1.0; 1.0 ≤VRI <2.0 indicated intermediate vascular reactivity, and VRI ≥2.0 was grouped as good vascular reactivity. RESULTS: Seven KT patients (10.9%) were categorized as poor vascular reactivity, 24 KT patients (37.5%) were grouped as intermediate vascular reactivity, and 33 KT patients had good vascular reactivity. Advanced age (r = -0.372, P = 0.002) and serum alkaline phosphate (ALP) level (r = -0.341, P = 0.006) were negatively correlated with VRI. However, serum myostatin level (r = 0.430, P < 0.001) was positively correlated with VRI. In multivariable forward stepwise linear regression analysis, high serum level of myostatin (ß = 0.441, adjusted R 2 change = 0.171; P < 0.001), advanced age (ß = -0.317, adjusted R 2 change = 0.138; P = 0.003), and serum ALP level (ß = -0.270, adjusted R 2 change = 0.060; P = 0.011) were significantly associated with VRI in KT patients. CONCLUSION: Our study showed that fasting myostatin level was positively associated with VRI and endothelial function among KT patients.

Association of endothelial dysfunction with sarcopenia and muscle function in a relatively young cohort of kidney transplant recipients.

BACKGROUND: Sarcopenia and endothelial dysfunction are both common among kidney transplant (KT) recipients. We aimed to evaluate the association between endothelial dysfunction and sarcopenia, as well as its individual components. METHODS: Vascular reactivity index (VRI), skeletal muscle index (SMI = skeletal muscle mass/height2), handgrip strength (HGS), and 6-meter usual gait speed (GS) were measured in 95 KT recipients. Low SMI was defined as SMI less than 10% of the sex-specific reference values from Chinese adults; low HGS as HGS < 28 kg for men and < 18 kg for women; slow GS as GS below 1.0 m/s. Sarcopenia was diagnosed based on the presence of low SMI as an essential criterion, accompanied by either low HGS or slow GS. Vascular reactivity was classified as being indicative of poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), or good (VRI ≥ 2.0) vascular reactivity. RESULTS: Of the 95 patients, aged 45.2 ± 10.9 years, 11.6% had sarcopenia and 13.7% had poor vascular reactivity. Patients with sarcopenia were lower in body mass index (p = 0.001) and VRI (p = 0.041), and have a higher proportion of low muscle mass (p < 0.001), low HGS (p < 0.001), and slow GS (p = 0.001). Patients with poor vascular reactivity have a higher proportion of sarcopenia (p = 0.005), low HGS (p = 0.006), and slow GS (p = 0.029). Multivariate logistic regression analysis showed that patients in the poor VRI group were significantly associated with sarcopenia (odds ratio, OR = 6.17; 95% confidence interval [1.06-36.04]; p = 0.043), comparing to those with good VRI. We further analysed the effects of VRI on individual components of sarcopenia and found that VRI predicted slow GS significantly (OR = 0.41; 95% CI = [0.21-0.79]; p = 0.007), but not low SMI (OR = 1.15; 95% CI [0.53-2.49]; p = 0.718) and HGS (OR = 0.59; 95% CI [0.31-1.16]; p = 0.125). CONCLUSIONS: We concluded that endothelial dysfunction is a key determinant of sarcopenia in KT recipients. Furthermore, endothelial dysfunction is more closely related to gait speed than muscle mass and strength.

Association of Low Serum l-Carnitine Levels with Peripheral Arterial Stiffness in Patients Who Undergo Kidney Transplantation.

l-carnitine is an important co-factor in fatty-acid metabolism, and its deficiency is associated with insulin resistance, which is independently associated with arterial stiffness. This study evaluated the relationship between serum l-carnitine level and peripheral arterial stiffness (PAS) in kidney transplantation (KT). Fasting blood samples were collected from 65 patients who underwent KT. We measured the brachial-ankle pulse wave velocity, and 36 patients (55.4%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.001), hypertension (p = 0.033), and metabolic syndrome (p = 0.044); higher waist circumference (p = 0.010), systolic blood pressure (p = 0.002), serum triglyceride level (p = 0.040), insulin level (p = 0.002), and homeostasis model assessment of insulin resistance (p = 0.002); lower high-density lipoprotein cholesterol (p = 0.036) and serum l-carnitine levels (p < 0.001); older age (p = 0.041); and a longer KT duration (p = 0.025) than those without PAS. Statistical analysis revealed an independent association between PAS in KT and KT duration (95% confidence interval (CI): 1.003-1.054, p = 0.029) and serum l-carnitine levels (95% CI: 0.842-0.998, p = 0.044). The area under the receiver operating characteristic curve indicated that the diagnostic power of l-carnitine to predict PAS was 0.789 (95% CI: 0.670-0.881, p < 0.001). Serum-free l-carnitine level is negatively associated with PAS in patients who undergo KT.

Serum adipocyte fatty acid-binding protein level is associated with arterial stiffness quantified with cardio-ankle vascular index in kidney transplant patients.

BACKGROUND: Arterial stiffness is an established marker of cardiovascular risk and an independent predictor of cardiovascular disease (CVD) events and mortality in kidney transplant (KT) patients. Adipocyte fatty acid-binding protein (A-FABP), a novel adipokine, is positively associated with atherosclerosis. The present study evaluated the relationship between fasting circulating A-FABP and peripheral arterial stiffness using the cardio-ankle vascular index (CAVI) in KT patients. METHODS: Fasting blood samples were collected from 74 KT patients, and serum A-FABP levels were measured using an enzyme immunoassay. CAVI was calculated using a waveform device (CAVI-VaSera VS-1000). The cutoff values for high and low levels of arterial stiffness were defined by the CAVI values of ≥9 and <9, respectively. RESULTS: Thirty-four patients (45.9%) were classified into the high arterial stiffness group. Compared with the low arterial stiffness group, the high arterial stiffness group had higher values for age (p = 0.015), systolic blood pressure (p < 0.001), pulse pressure (p < 0.001), duration of kidney transplantation (p = 0.005), serum total cholesterol and triglyceride levels (p = 0.033 and 0.047, respectively), glomerular filtration rate (p = 0.019), fasting glucose levels (p = 0.012), and serum A-FABP levels (p < 0.001). Multivariate forward stepwise linear regression analysis showed that age (p = 0.004), systolic blood pressure (p = 0.001), and serum A-FABP levels (p = 0.003) were independent predictors of CAVI value in KT patients. CONCLUSION: Serum fasting A-FABP level is positively associated with peripheral arterial stiffness in KT patients.

Application of Bacteriophage-containing Aerosol against Nosocomial Transmission of Carbapenem-Resistant Acinetobacter baumannii in an Intensive Care Unit.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is associated with nosocomial infections worldwide. Here, we used phage as a potential agent to evaluate the efficacy of daily cleaning practices combined with a bacteriophage-containing aerosol against CRAB. METHODS: A two-phase prospective intervention study was performed at a 945-bed public teaching hospital. From March to December 2013, we performed terminal cleaning using standard procedures plus an aerosol with active bacteriophage in the intensive care units to evaluate the impact on nosocomial incidence density, carbapenem-resistance rates and antimicrobial drug consumption amounts. Patients with culture proven CRAB infection were transferred to the isolation room when the phage aerosol cleaning had been completed. RESULTS: A total of 264 new acquisitions of CRAB were identified in the intensive care units (191 in the pre-intervention period and 73 in the intervention period). The rates of new acquisitions of CRAB in the intensive care units decreased from 8.57 per 1000 patient-days in the pre-intervention period to 5.11 per 1000 patient-days in the intervention period (p = 0.0029). The mean percentage of resistant isolates CRAB decreased from 87.76% to 46.07% in the intensive care units (p = 0.001). All of the antimicrobials showed a significant reduction in consumption except imipenem. CONCLUSIONS: The bacteriophage was successful in decreasing the rates of infection caused by CRAB across intensive care units in a large teaching hospital.

Serum Sclerostin as an Independent Marker of Peripheral Arterial Stiffness in Renal Transplantation Recipients: A Cross-Sectional Study.

Wnt/ß-catenin signaling pathway is thought to be implicated in the development of arterial stiffness and vascular calcification. As a Wnt signaling pathway inhibitor, it is interesting to investigate whether sclerostin or dickkopf-1 (DKK1) level is correlated with arterial stiffness in renal transplant (RT) recipients. Fasting blood samples were obtained for biochemical data, sclerostin, DKK1, and osteoprotegerin (OPG) determinations. In this study, we applied automatic pulse wave analyzer (VaSera VS-1000) to measure brachial-ankle pulse wave velocity and either sides of brachial-ankle pulse wave velocity value, which greater than 14.0 m/s was determined as high arterial stiffness. Among 68 RT recipients, 30 patients (44.1%) were in the high arterial stiffness group. Compared with patients in the low arterial stiffness group, patients in the high arterial stiffness group had higher prevalence of hypertension (P = 0.002), diabetes (P < 0.001), metabolic syndrome (P = 0.025), longer posttransplant duration (P = 0.005), higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.018), and higher fasting glucose (P = 0.004), total cholesterol (P = 0.042), blood urea nitrogen (P = 0.020), phosphorus (P = 0.042), and sclerostin levels (P = 0.001). According to our multivariable forward stepwise linear regression analysis, age (ß = 0.272, P = 0.014), phosphorus (ß = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; ß = 0.222, P = 0.046) were positively associated with sclerostin levels, and multivariate logistic regression analysis, sclerostin (odds ratio 1.052, 95% confidence interval 1.007-1.099, P = 0.024), and posttransplant duration (odds ratio 1.024, 95% confidence interval 1.004-1.045, P = 0.019) were the independent predictors of peripheral arterial stiffness in RT recipients. In this study, serum sclerostin level, but not DKK1, was proved to be involved in the pathogenetic process of peripheral arterial stiffness in RT recipients.

Serum adiponectin is a negative predictor of central arterial stiffness in kidney transplant patients.

BACKGROUND: The role of adiponectin in arterial stiffness and its relationship to cardiovascular disease is not fully demonstrated and needs further elaboration. In this study, the association between adiponectin level and arterial stiffness is studied among kidney transplant patients. MATERIAL AND METHODS: Anthropometric data and biochemical data including fasting glucose, lipid profile, renal function and serum adiponectin were determined in 55 kidney transplant patients. Central arterial stiffness was measured and presented by carotid-femoral pulse wave velocity. RESULTS: Univariate linear analysis showed that body weight, waist circumference, brachial pulse pressure and body mass index were correlated positively with carotid-femoral pulse wave velocity in this patient group. However, logarithmically transformed adiponectin level (log-adiponectin) correlated negatively with carotid-femoral pulse wave velocity. In multivariate regression analysis of factors significantly associated with carotid-femoral pulse wave velocity, it showed that both log-adiponectin (ß = -0.427; R(2) = 0.205, p = 0.001) and body weight (ß = 0.327; R(2 )=( )0.106, p = 0.007) were independently predictive of central arterial stiffness. CONCLUSION: Our study suggests that fasting serum adiponectin is negatively associated with carotid-femoral pulse wave velocity, hence arterial stiffness, in kidney transplant patients.

Serum osteoprotegerin levels associated with the aortic augmentation index in renal transplant recipients.

OBJECTIVES: Arterial stiffness is recognized as an independent risk factor for cardiovascular morbidity and mortality. Recent studies found that osteoprotegerin (OPG) is associated with arterial stiffness and may reflect endothelial dysfunction. The aim of this study was to evaluate the relationship between fasting serum OPG levels and the aortic augmentation index (AIx) in renal transplant recipients. MATERIALS AND METHODS: Fasting blood samples were obtained from 66 renal transplant recipients. The aortic AIx was measured using a validated tonometry system (SphygmoCor). Serum OPG levels were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Univariate linear analysis of the aortic AIx in renal transplant recipients revealed that body fat mass (r = 0.377, p = 0.002), aortic diastolic blood pressure (DBP; r = 0.307, p = 0.020), triglycerides (r = 0.260, p = 0.035), and logarithmically transformed OPG (log-OPG, r = 0.402, p < 0.001) were positively correlated, whereas height (r = 0.361, p = 0.004) and body weight (r = 0.212, p = 0.041) were negatively correlated with the aortic AIx in renal transplant recipients. Multivariate forward stepwise linear regression analysis of the factors significantly associated with the aortic AIx showed that log-OPG (R2 = 0.213, p < 0.001), height (R2 = 0.081, p = 0.009), and aortic DBP (R2 = 0.058, p = 0.022) were independent predictors of the aortic AIx in renal transplant recipients. CONCLUSION: These results suggest that the serum fasting OPG level is associated with the aortic AIx in renal transplant recipients.

High Serum Osteoprotegerin Is Associated with Arterial Stiffness in Kidney Transplant Patients.

Osteoprotegerin (OPG) is a cytokine that regulates bone resorption by inhibiting osteoclastogenesis, and OPG has been implicated in the process that causes vascular stiffness. An increase in serum OPG level has been associated with the development of arterial stiffness. Kidney transplant (KT) patients are susceptible to aortic stiffness, which is considered to be a predictor of cardiovascular events in this patient population. Carotid-femoral pulse wave velocity (cfPWV) has emerged as a gold standard for non-invasive evaluation of aortic stiffness. The aim of this study was to evaluate the relationship between serum OPG concentration and cfPWV among KT patients. Fasting blood samples were obtained from 57 KT patients and their cfPWV was measured using applanation tonometry. The serum OPG levels were measured using an enzyme-linked immunosorbent assay. Univariable linear regression analysis showed that the cfPWV in KT patients was significantly and positively correlated with age, body weight, waist circumference, body mass index, log-creatinine, systolic blood pressure, diastolic blood pressure, pulse pressure, and the log-OPG concentration. KT patients with metabolic syndrome had higher cfPWV values than those without metabolic syndrome (P = 0.036), which indicates a higher incidence of aortic stiffness in this patient population. Multivariable forward stepwise linear regression analysis of the significant variables showed that the log-OPG (P = 0.001), the log-creatinine (P = 0.004), and the SBP (P = 0.005) remained as independent and positive predictors of cfPWV values. These findings indicate that serum OPG levels are positively associated with cfPWV in KT patients.

Hypoadiponectinemia correlates with arterial stiffness in kidney transplantation patients.

BACKGROUND: Adiponectin is a fat-derived hormone produced and secreted exclusively by adipocytes that have anti-atherosclerotic effects. The aim of this study was to evaluate the relationship between fasting serum adiponectin levels and arterial stiffness among kidney transplant (KT) patients. METHODS: Fasting blood samples were obtained from 69 KT patients. Brachial-ankle pulse wave velocity (baPWV) was measured in the right or left brachial artery to the ankle segments using an automatic pulse wave analyzer. Plasma adiponectin levels were measured using a commercial enzyme-linked immunosorbent assay kit. Left or right baPWV values of >14.0 m/s were used to define the high arterial stiffness group. RESULTS: Thirty-five KT patients (35/69; 50.7 %) were defined in high arterial stiffness group. Diabetes (P = 0.013), smoking (P = 0.001), KT duration (P < 0.001), body weight (P = 0.013), waist circumference (P = 0.013), body mass index (P = 0.001), fasting glucose (P = 0.013), systolic blood pressure (P < 0.001), diastolic blood pressure (P = 0.008), and pulse pressure (P = 0.003) were higher, while serum adiponectin level (P = 0.004) was lower in high arterial stiffness group compared with low arterial stiffness group. Multivariate logistic regression analysis showed that adiponectin (odds ratio 0.90, 95 % confidence interval 0.81-0.99, P = 0.034) was still the independent predictors of arterial stiffness among the KT patients. CONCLUSION: Serum fasting adiponectin level was inversely associated with arterial stiffness among KT patients.

Fasting serum long-acting natriuretic peptide correlates with the ankle brachial index in renal transplant recipients.

OBJECTIVES: Peripheral arterial diseases associated with an increased risk of death in kidney transplant patients. Natriuretic peptide has anti-atherosclerotic effects. We sought to evaluate the relation between ankle-brachial index and fasting serum long-acting natriuretic peptide concentrations in kidney transplant patients. MATERIALS AND METHODS: Fasting blood samples were obtained from 69 kidney transplant patients. Serum long-acting natriuretic peptide concentrations were measured using a commercially available enzyme immunoassay kit. Left or right ankle-brachial index values that were < 0.9 were included in the low ankle-brachial index group. RESULTS: Fifteen patients (21.7%) were enrolled in the low ankle-brachial index group. Increased waist circumference (P = .013), higher serum total cholesterol levels (P = .019), higher triglyceride levels (P = .002), and decreased serum long-acting natriuretic peptide concentrations (P = .006) were noted in the low ankle-brachial index group. Univariate linear regression analysis indicated that the left/right ankle-brachial index values of the subjects were negatively correlated with serum triglycerides (P = .008 or P < .001) and fasting glucose levels (P = .034 or P = .012), but were positively correlated with long-acting natriuretic peptide concentrations (P = .011 or P = .011). Multivariate forward stepwise linear regression analyses of the significant variables revealed that serum triglycerides and long-acting natriuretic peptide levels were independent predictors of the left/right ankle-brachial index values of kidney transplant patients. CONCLUSIONS: Serum long-acting natriuretic peptide concentrations correlate positively with ankle-brachial index values among the kidney transplant patients.

N-terminal pro-B-type natriuretic peptide is associated with arterial stiffness measured using the cardio-ankle vascular index in renal transplant recipients.

AIM: Arterial stiffness is an established cardiovascular risk marker and an independent predictor of cardiovascular events and mortality in various groups of patients, including renal transplant recipients. Recent studies have noted that B-type natriuretic peptide (BNP) acts as a local paracrine molecule that modulates endothelial permeability and regeneration. The aim of this study was to evaluate the relationship between the serum N-terminal pro-BNP (NT-pro-BNP) level and arterial stiffness in renal transplant recipients. METHODS: Fasting blood samples were obtained from 66 renal transplant recipients. The cardio-ankle vascular index was calculated using the waveform device (CAVI-VaSera VS-1000). The serum NTpro-BNP levels were measured using an electrochemiluminescence immunoassay. A CAVI value of ≥9 was used to define a high level of arterial stiffness. RESULTS: Thirty-two patients (48.5%) were classified into the high arterial stiffness group. Diabetes (p=0.030), smoking (p<0.001), duration of kidney transplantation (p=0.001), body weight (p=0.014), waist circumference (p=0.022), body mass index (p=0.001) and the fasting glucose (p=0.021) and serum NT-pro-BNP (p<0.001) levels were higher in the high arterial stiffness group than in the low arterial stiffness group. A multivariate forward stepwise linear regression analysis showed that the log-NT-pro-BNP level (ß: 0.459, p<0.001) remained an independent predictor of the CAVI value in the renal transplant recipients. CONCLUSIONS: The serum fasting NT-pro-BNP level is associated with arterial stiffness in renal transplant recipients.

Inverse association of serum long-acting natriuretic peptide and bone mineral density in renal transplant recipients.

OBJECTIVE: Our aim was to evaluate the relationship between bone mineral density (BMD) and fasting serum long-acting natriuretic peptide (LANP) concentration in renal transplant recipients. PATIENTS AND METHODS: Fasting blood samples were obtained from 65 renal transplant recipients. BMD was measured using dual energy X-ray absorptiometry in lumbar vertebrae (L2-L4). Serum LANP levels were measured using a commercial enzyme immunoassay kit. RESULTS: Six patients (9.2%) had osteoporosis and 28 patients (43.1%) had osteopenia in renal transplant recipients. Increased serum LANP (p<0.001) was significantly correlated with low lumbar T-score cut-off points between groups (normal, osteopenia, and osteoporosis) in renal transplant recipients. Female patients had lower lumbar BMD than male renal transplant recipients (p=0.027). Univariate linear regression analysis indicated that lumbar BMD were positively correlated with height (p=0.038), body weight (p=0.003), and body mass index (BMI; p=0.019), whereas negatively correlated with LANP (p=0.004) among the renal transplant recipients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that body weight (R(2) change=0.132; p=0.006) and LANP (R(2) change=0.093; p=0.008) were the independent predictors of lumbar BMD values in the renal transplant recipients. CONCLUSION: Serum LANP concentration correlates negatively with lumbar BMD values in renal transplant recipients.

Hyperleptinemia positively correlated with metabolic syndrome in renal transplant recipients.

OBJECTIVE: Our aim was to evaluate the relationship between metabolic syndrome and fasting serum leptin concentration in renal transplant recipients. PATIENTS AND METHODS: Fasting blood samples were obtained from 55 renal transplant recipients. Metabolic syndrome and its components were defined using the diagnostic criteria of the International Diabetes Federation. RESULTS: Thirteen patients (23.6%) had metabolic syndrome. Fasting leptin concentrations were positively correlated with metabolic syndrome (p=0.003). Univariate linear regression analysis indicated fasting serum leptin values were positively correlated with waist circumference (r=0.284; p=0.036), body mass index (r=0.358; p=0.007), body fat mass (r=0.610; p<0.001), triglycerides (r=0.268; p=0.048), high-sensitivity C-reactive protein (hs-CRP) (r=0.377; p=0.005), triceps skinfold (r=0.335; p=0.012), and mid-arm fat area (r=0.351; p=0.009). Multivariate forward stepwise linear regression analysis of the significant variables revealed that body fat mass (R2 change=0.373; p<0.001) and hs-CRP (R2 change=0.045; p=0.049) were the independent predictors of fasting serum leptin concentration. CONCLUSION: Serum leptin concentration correlates positively with metabolic syndrome in renal transplant recipients.