Yen-g Chen

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.

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

Hsu B‐G, Ho G‐J, Lee C‐J, Yang Y‐C, Chen Y‐C, Shih M‐H, Lee M‐C. Inverse association of serum long‐acting natriuretic peptide and bone mineral density in renal transplant recipients. 
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01575.x. 
© 2011 John Wiley & Sons A/S.

Muscarinic receptor M3 mediates human gallbladder contraction through voltage-gated Ca2+ channels and Rho kinase.

Abstract Objective. Muscarinic receptors mediate contraction of the human gallbladder through unclear receptor subtypes. The aim of the present study was to characterize muscarinic acetylcholine receptors mediating contraction of the human gallbladder. Materials and methods. Contraction of human gallbladder muscle strips caused by agonists carbachol and muscarine was measured and the inhibition of carbachol-induced contraction by muscarinic receptor antagonists was evaluated. Reverse transcription polymerase chain reaction was performed to determine the existence of muscarinic receptor subtypes. Results. Carbachol and muscarine caused concentration-dependent contraction of gallbladder strips. Four receptor antagonists, including atropine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), methoctramine, and pirenzepine, inhibited the carbachol-induced contraction. The relative inhibitory potency of these receptor antagonists was atropine > 4-DAMP > methoctramine > pirenzepine. The antagonist affinity estimates (pA2 values) correlated with the known affinities at M3, M4, and M5 muscarinic receptors. In addition, the M4-selective antagonist muscarinic toxin 3 did not inhibit and the M5-selective positive allosteric modulator VU0238429 did not potentiate carbachol-induced gallbladder contraction. This suggests that M3 muscarinic receptors mediate the muscarinic response predominantly. The contractile response of carbachol was attenuated by the voltage-gated Ca2+ channel inhibitor nifedipine and Rho-kinase inhibitor H-1152, but not affected by protein kinase C inhibitor chelerythrine. This implies the involvement of voltage-gated Ca2+ channel and Rho kinase but not protein kinase C. Conclusions. These results suggest a major role of M3 muscarinic receptors mediating the human gallbladder contraction through voltage-gated Ca2+ channels and Rho kinase. M3-selective muscarinic receptor antagonists could be of therapeutic importance in the treatment of biliary motility disorders.

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

AbstractWnt/&bgr;-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 (&bgr; = 0.272, P = 0.014), phosphorus (&bgr; = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; &bgr; = 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

Abstract 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 (β = −0.427; R2 = 0.205, p = 0.001) and body weight (β = 0.327; R2 = 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.

Estrogen and G protein-coupled estrogen receptor agonist G-1 cause relaxation of human gallbladder

Objective: Estrogen interacts with a membrane receptor, G protein-coupled estrogen receptor (GPER). It was reported that 17β-estradiol was able to inhibit contraction of the human colon and cause relaxation of the guinea pig gallbladder, however, the involvement of GPER was not clarified. The aim of the present study was to investigate the effect of estrogen on human gallbladder motility and the possible role of GPER. Materials and Methods: Relaxation of human gallbladder strips were measured using isometric transducers. Expression of GPER was evaluated by reverse transcription polymerase chain reaction (PCR), realtime PCR, and immunohistochemistry. Results: In human gallbladder strips, 17β-estradiol and G-1 elicited marked and rapid relaxation, whereas tamoxifen produced mild concentration-dependent relaxation. The relative efficacies to cause relaxation were as follows: 17β-estradiol = G-1 > tamoxifen. The relaxant response of 17β-estradiol was not attenuated by tetrodotoxin or conotoxin GVIA. This implies that nerve stimulation was not involved in the 17β-estradiol-induced gallbladder relaxation. Analysis by reverse transcription PCR and real-time PCR showed that GPER was expressed in the human gallbladder. Further analysis by immunohisto-chemistry revealed that GPER was expressed in the gallbladder muscle. This suggests that 17β-estradiol relaxes the human gallbladder via GPER. Conclusion: These results demonstrate for the first time that 17β-estradiol and GPER agonist G-1 cause relaxation of the human gallbladder, probably through GPER. Estrogen might play an important role in the control of human gallbladder motility.

Hyperleptinemia is associated with the aortic augmentation index in kidney transplant recipients

Objective: Increased circulating leptin, a marker of leptin resistance, is common in patients with obesity and is also an independent factor in prediction of cardiovascular disease. The aim of this study was to evaluate the relationship between fasting serum leptin levels and the aortic augmentation index (AIx) in kidney transplant recipients. Materials and Methods: Fasting blood samples were obtained from 70 kidney transplant recipients. The aortic AIx was measured using a validated tonometry system (SphygmoCor). Plasma leptin levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Simple linear analysis of the aortic AIx in kidney transplant recipients showed that body fat mass (P = 0.002), diastolic blood pressure (DBP) (P = 0.020), logarithmically transformed triglycerides (P = 0.035), and leptin (P < 0.001) were positively correlated, while height (P = 0.004) and the glomerular filtration rate (P = 0.022) were negatively correlated with the aortic AIx in kidney transplant recipients. Forward stepwise linear regression analysis of the factors significantly associated with the aortic AIx showed that leptin (P < 0.001), DBP (P = 0.014), and body height (P = 0.036) were independent predictors of the aortic AIx in kidney transplant recipients. Conclusion: These results suggest that the serum fasting leptin level is associated with the aortic AIx in kidney transplant recipients.

Inverse Association of N-terminal pro-B-type natriuretic Peptide Level with Metabolic Syndrome in Kidney Transplantation Patients

BACKGROUND Low levels of natriuretic peptide may activate the renin-angiotensin-aldosterone system, which may contribute to the development of obesity. Therefore, in study we aim to evaluate the relationship between metabolic syndrome (MetS) and serum N-terminal pro‒B-type natriuretic peptide (NT-proBNP) concentration in kidney transplant recipients. METHODS Fasting blood samples were obtained from 66 kidney transplant recipients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. RESULTS A total of 20 patients (30.3%) had MetS. Hypertension, prevalence of diabetes, use of statin or fibrate, body weight, body mass index, waist circumference, body fat mass, and levels of systolic blood pressure, total cholesterol, triglyceride, blood urea nitrogen, insulin, and HOMA-IR were higher, whereas the levels of high-density lipoprotein cholesterol and NT-proBNP were lower in patients with MetS. Logarithmically transformed creatinine and log-HOMA-IR were associated with NT-proBNP levels in a multivariable linear regression analysis. Multivariate logistic regression analysis revealed that NT-proBNP was an independent predictor of MetS in kidney transplant recipients. CONCLUSION Our study has revealed that fasting level of NT-proBNP was negatively associated with MetS and that serum creatinine and HOMA-IR were independent predictors of serum NT-proBNP level in kidney transplant recipients.

Associations Between High Serum Adipocyte Fatty Acid Binding Protein and First Hospitalization in Kidney Transplantation Patients

Introduction Adipocyte fatty acid-binding protein (A-FABP) is an adipokine and predicts the incidence of metabolic syndrome and type 2 diabetes mellitus and is an independent association with atherosclerosis. This study was evaluated the association between serum A-FABP levels and future first hospitalization events in patients with kidney transplantation (KT). Materials and Methods A total of 72 KT patients were enrolled in this study from January through April 2012. The primary end point was the incidence of first hospitalization. All patients are follow-up until June 2017.Fasting blood samples were obtained from 74 KT patients. Serum A-FABP levels were determined using a commercially available enzyme immunoassay. Results During a median 65-month follow-up, Forty-nine first hospitalization events occurred. Compared with serum median A-FABP levels, female KD patient had higher A-FABP levels(P = 0.033) and serum A-FABP level was positively associated with body mass index (P = 0.036), body fat mass (P = 0.004), systolic blood pressure (P = 0.003), total cholesterol (P = 0.014), triglyceride (P = 0.010), blood urea nitrogen (P = 0.001), creatinine (P = 0.032), while negatively associated with height (P = 0.029), glomerular filtration rate (P = 0.008), respectively. KT patients with first hospitalization events and higher prevalence of diabetes (P = 0.027), hypertension (P = 0.049), higher body fat mass (P = 0.024), and higher serum A-FABP levels (P = 0.011) compared to subjects without first hospitalization events. The Kaplan–Meier analysis showed that the cumulative incidence of the first hospitalization events in the high A-FABP group (median A-FABP concentration of ≥ 29.05 ng/mL) was greater than that in the low A-FABP group (log-rank P = 0.018). By multivariate Cox analysis showed that hypertension (hazard ratio (HR): 2.134, 95% confidence interval (CI): 1.190–3.828, P = 0.011) and serum A-FABP levels (HR: 1.010, 95% CI: 1.000–1.019, P = 0.047) was independently associated with first hospitalization events in KT patients. Conclusion The results of our study showed that the serum A-FABP level is a biomarker for future first hospitalization events in KT patients. Further prospective studies are needed to confirm the mechanisms underlying this association. Figure. No caption available.

Elevated serum osteoprotegerin may predict peripheral arterial disease after kidney transplantation: a single-center prospective cross-sectional study in Taiwan

Background Osteoprotegerin (OPG) is a potential biomarker for severity and complications of cardiovascular diseases. Peripheral arterial disease (PAD) is associated with an increased risk of death in kidney transplantation (KT) patients. This prospective cross-sectional study evaluated the relationship between serum OPG and PAD in KT patients. Methods Seventy-four KT patients were enrolled for this PAD study. Fasting blood samples were obtained to measure serum OPG levels by using enzyme-linked immunosorbent assay kits. The ankle-brachial index (ABI) of less than 0.9 was applied for PAD diagnosis. Results Thirteen patients (17.6%) were diagnosed with PAD. Diabetes (P = 0.025), smoking (P = 0.010), and increased OPG levels (P = 0.001) were significantly more frequent in the PAD group. Multivariate logistic regression analysis showed that serum OPG (odds ratio [OR], 1.336; 95% CI [1.108–1.611]; P = 0.002) and diabetes (OR, 7.120; 95% CI [1.080–46.940]; P = 0.041) were independent predictors of PAD in KT patients. The area under the receiver operating characteristic (ROC) curve determined that the probability of a serum OPG level of 7.117 pg/L in predicting PAD in KT patients was 0.799 (95% CI [0.690–0.884]; P < 0.001). Discussion Exploration of reliable biomarkers for early identification of vascular risk is crucial for KT patients. Elevated serum OPG levels may predict PAD in KT patients with cutoff value of 7.117 pg/L.