Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients.

BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein that inhibits osteoclast differentiation and activity. OPG-deficient mice develop severe osteoporosis and medial arterial calcification. The expression of OPG is detected in early atherosclerotic lesions in non-uraemic patients. We examined whether serum OPG is associated with aortic calcification in haemodialysis patients. METHODS: Serum OPG was measured in 102 patients who were undergoing haemodialysis. The aortic calcification index (ACI) was assessed by computed tomography scans. RESULTS: Serum OPG level, measured by enzyme-linked immunosorbent assay, was significantly greater in patients with higher ACI than in those with lower ACI. There was a direct relationship between ACI and serum OPG levels and a positive association between OPG and ACI (r = 0.483, P<0.0001). Multiple regression analyses indicated that serum OPG levels were independently associated with the severity of aortic calcification (P<0.0001). CONCLUSIONS: These findings show that serum OPG levels are associated with the extent of vascular calcification, suggesting that OPG may be involved in the development of vascular calcification in haemodialysis patients.     

Soluble osteopontin and vascular calcification in hemodialysis patients.

BACKGROUND: Vascular calcification often occurs in patients with uremia. As osteopontin (OPN) is not only involved in the physiological but also the pathological calcification of tissues, OPN may be associated with the pathogenesis of aortic calcification in hemodialysis (HD) patients. METHODS: We examined the expression of OPN in atherosclerotic aortas of HD patients. In addition, we performed a prospective longitudinal study by using CT scans to detect aortic calcifications and by measuring the plasma OPN concentration by ELISA in HD patients (20 men, 16 women; mean age 55.2 +/- 21.3 years) and in healthy volunteers (18 men, 17 women; mean age 54.0 +/- 13.2 years). RESULTS: By immunohistochemical staining, OPN was abundantly localized in atherosclerotic plaques of HD patients. The macrophages surrounding the atheromatous plaques were identified as the OPN-expressing cells. We furthermore found that the concentration of soluble plasma OPN was significantly higher in HD patients as compared with the concentrations in age-matched healthy volunteers (837.3 +/- 443.2 vs. 315.1 +/- 117.4 ng/ml, p < 0.01). The OPN concentration was positively correlated with the aortic calcification index in HD patients (r = 0.749, p < 0.01). CONCLUSION: These data suggest that OPN, secreted by macrophages, plays a role in the calcification of atheromatous plaques in HD patients.     

Predictive value of serum macrophage colony-stimulating factor for development of aortic calcification in haemodialysis patients: a 6 year longitudinal study.

BACKGROUND: Accelerated atherosclerosis is a major complication in patients on haemodialysis (HD). Macrophage colony-stimulating factor (MCSF) is a representative regulator of activation of monocytes and macrophages, and plays important roles in the development of atherosclerosis in HD patients. However, the long-term predictive value of the serum MCSF level for the development of aortic calcification under HD conditions has not been reported. METHODS: Serum MCSF level was measured in 40 HD patients. The aortic calcification index (ACI) was also calculated on computed tomography once each year for 6 years. Predictive value was examined by logistic regression analysis. RESULTS: At baseline, there was a significant correlation between serum MCSF and ACI (r = 0.43, P<0.01). A significant increase in ACI was first noted at 4 years post-baseline and the increase was maintained thereafter in the high MCSF group. No such changes were noted in the low MCSF group. Univariate analysis identified high levels of calcium x phosphorus product, triglyceride, C-reactive protein (CRP), MCSF and presence of diabetes mellitus as significant predictors for increased ACI at 6 years. However, among these five factors, high levels of CRP and MCSF were the only independent and significant predictors (odds ratio = 24.0, P = 0.03 and odds ratio = 22.8, P = 0.02, respectively). CONCLUSIONS: Our results demonstrated that MCSF is associated with the process of atherosclerosis in HD patients. Furthermore, the serum MCSF level is an independent long-term predictor of increased ACI. These results provide useful information for preventive strategies against atherosclerotic disease under HD conditions.     

Association between circulating leptin and soluble receptors for tumor necrosis factor-alpha in hemodialysis patients.

BACKGROUND: The expression of leptin, an adipocyte-derived protein, is regulated by tumor necrosis factor-alpha (TNF-alpha). Since circulating leptin levels adjusted for body fat mass are reported to be increased in dialysis patients, we examined if the TNF-alpha system may influence blood leptin levels in hemodialysis (HD) patients. PATIENTS AND METHODS: Sixty-three stable HD patients who had no signs of infection, collagen disease or malignancy were enrolled in the study (age: 63 +/- 1 years, duration of HD: 14 +/- 1 years, male/female = 34/29). We measured serum leptin, TNF-alpha, soluble receptors for TNF-alpha (sTNFR p55, p80) and interleukin-6 (IL-6) concentrations with ELISA kits. Body fat mass was determined using DEXA. To evaluate the potential association between serum leptin and the TNF-alpha system, we compared serum leptin and sTNFR levels, which has been validated as a sensitive marker of activation of the TNF-alpha system. RESULTS: Serum leptin levels were significantly higher in female patients compared to male patients (14.07 +/- 3.60 vs. 4.26 +/- 0.85 ng/ml, p < 0.005). A strong correlation was found between serum leptin levels and estimated body fat mass both in males (r = 0.742, p < 0.0001) and females (r = 0.769, p < 0.001), respectively. Serum TNF-alpha, sTNFR p55, p80 and IL-6 levels were significantly increased in HD patients compared to normal subjects. However, no association was found between serum leptin and serum TNF-alpha, sTNFR p55, p80 and IL-6 levels. Serum leptin levels were significantly correlated with the atherosclerotic index both in men (r = 0.382, p = 0.027) and women (r = 0.281, p = 0.041). In contrast, there was no relationship between circulating leptin values and serum albumin, transferrin, creatinine levels, or normalized protein catabolic rate in each sex. CONCLUSION: These findings suggested that serum leptin is independent of the TNF-alpha system, and is mainly correlated with body fat volume in HD patients. Elevation of circulating leptin may be associated with the disturbance of the serum lipid profile rather than malnutrition in patients receiving long-term HD.     

Carotid atherosclerosis is a predictor of coronary calcification in chronic haemodialysis patients.

BACKGROUND: Coronary artery calcification scores (CACS) calculated by electron beam computed tomography (EBCT) have been correlated with atherosclerotic burden in the non-uraemic population. However, the validity of this test in chronic haemodialysis patients (HD) is currently uncertain. In the present cross-sectional study, associations between carotid atherosclerosis and coronary calcification in HD patients are investigated. METHODS: We studied 79 chronic HD patients (39 male, 40 female; mean age, 45+/-12 years). The mean time on HD was 68+/-54 months (range, 6-187 months). In these patients, we measured serum calcium, phosphorus, total cholesterol, cholesterol subgroups and iPTH levels. EBCT, echocardiography, and high-resolution B-mode carotid Doppler ultrasonography were also performed. RESULTS: Plaque-positive HD patients had significantly higher CACS than plaque-negative patients (851+/-199 vs 428+/-185, mean+/-SE, P = 0.006). Coronary calcification scores were correlated with serum phosphorus (r = 0.37; P = 0.001). Only 8 of the 24 HD patients without coronary calcification had carotid plaques (33%), whereas 34 of the 53 patients with coronary calcification had carotid plaques (64%) (P = 0.015). Carotid plaque scores were correlated with CACS (r = 0.40; P = 0.001). A stepwise linear regression (model r = 0.72; P<0.001) revealed that CACS (log-transformed data of CACS) was associated with age (P<0.001), time on dialysis (P = 0.004), serum phosphorus level (P = 0.016) and carotid plaque scores (P = 0.037). CONCLUSIONS: Atherosclerosis is independently associated with coronary artery calcification and with hyperphosphataemia in chronic HD patients. CACS appeared to be predictive of both coronary atherosclerosis and carotid atherosclerosis.     

Oxidized low density lipoprotein (Ox-LDL) as a marker of atherosclerosis in hemodialysis (HD) patients

AIM: To characterize the relationship between oxidative stress and atherosclerosis in HD patients. METHODS: Seventy-five HD patients were entered into the study. Ox-LDL was measured as a probe for peroxidation and compared to clinical atherosclerotic parameters. Prospective studies were also performed to assess the effects of vitamin E-bonded membrane on oxidative stress. RESULTS: Elderly patients tended to show elevated Ox-LDL (alpha = 0.060+/-0.021 ng/microg LDL protein/year, r = 0.35, p < 0.05). Levels of Ox-LDL in the patients with positive history for atherosclerotic diseases (3.1+/-0.4 ng/microg LDL protein, n = 36) were higher than those with a negative history (1.6+/-0.2, n = 39, p < 0.01). Further-more, ankle/brachial pressure index was negatively correlated to Ox-LDL (alpha = -0.052+/-0.012/ng/microg LDL protein, r = 0.42, p < 0.01). Application of vitamin E-bonded membrane for 10 months (-38+/-11%, n = 14, p < 0.05), but not synthetic membrane, ameliorated Ox-LDL. CONCLUSIONS: Our results indicate that Ox-LDL is elevated in aged HD patients. In addition, the present data provide evidence that vitamin E-bonded dialyzers attenuate oxidative stress. Finally, our findings suggest that Ox-LDL correlates to the magnitude of peripheral arterial diseases in HD patients.     

The relationship of visfatin levels to inflammatory cytokines and left ventricular hypertrophy in hemodialysis and continuous ambulatory peritoneal dialysis patients

Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-alpha, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-alpha levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 +/- 387.86 ng/mL) than hemodialysis (97.68 +/- 244.96 ng/mL,) and control (41.33 +/- 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-alpha (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = -0.305, p = 0.01), (r = -0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (beta = 0.369, p = 0.001) and IL-6 (beta = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-alpha. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index.     

Association between interleukin-6 and carotid atherosclerosis in hemodialysis patients

BACKGROUND: Interleukin-6 (IL-6) is associated with cardiovascular complications in general subjects. Although blood IL-6 is greatly elevated in hemodialysis (HD) patients, the role of IL-6 in the advance of atherosclerosis remains to be determined. METHODS: We conducted a cross-sectional study to investigate the relationship between circulating IL-6 and carotid atherosclerotic changes in 156 HD patients (age 58 +/- 1 years; time on HD treatment 13 +/- 1 years; 97 males and 59 females). Serum IL-6, IgG and IgA titers of Chlamydia pneumoniae antibodies, the intima-media thickness (IMT) and the cross-sectional intima-media area (IMarea) of the carotid arteries were measured by ultrasonography in each patient. RESULTS: Serum IL-6 levels were significantly higher in HD patients (2.04 +/- 0.16 pg/mL) compared to normal age-matched control subjects (0.31 +/- 0.06 pg/mL, N = 24). Circulating log IL-6 levels were positively correlated with IMT (r = 0.278, P < 0.01) and IMarea (r = 0.344, P < 0.01), respectively. A stepwise multiple regression analysis revealed that IL-6 became significant predictors for IMT and IMarea but not for aortic wall calcification at L2/3 vertebrae. Serum log IL-6 was significantly correlated with IgG (r = 0.277, P < 0.01) and IgA titers of anti-Chlamydia antibodies (r = 0.192, P < 0.02). Serum IgA anti-Chlamydia titers were also correlated with the maximal diameter of carotid plaque (r = 0.293, P < 0.04). CONCLUSIONS: These findings suggested that IL-6 is associated with the severity of carotid atherosclerosis in HD patients. Persistent chronic chlamydial infection may be related, in part, to the advance of carotid plaque enlargement in dialysis patients.     

Serum levels of macrophage colony-stimulating factor and aortic calcification in hemodialysis patients.

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 +/- 0.2 ng/ml) as compared with controls (1.5 +/- 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 +/- 0.2 ng/ml vs. polysulfone 3.8 +/- 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca x P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.     

Atherosclerosis and vascular calcification are independent predictors of left ventricular hypertrophy in chronic haemodialysis patients.

BACKGROUND: Accelerated atherosclerosis and vascular calcification are common in chronic haemodialysis (HD) patients. In this study, we aimed to investigate the relationship between left ventricular hypertrophy (LVH) in HD patients and atherosclerosis and vascular calcification measured by electron beam computed tomography (EBCT). METHODS: In a cohort of 118 HD patients (52 male, 66 female, mean age: 46+/-13 years), we measured biochemical parameters, including BUN, creatinine, albumin, haemoglobin, C-reactive protein and fibrinogen levels, and performed echocardiography, high-resolution B-mode carotid ultrasonography and EBCT in 85 of them. The degree of stenosis was measured at four different sites (communis, bulbus, interna and externa) in both carotid arteries. Carotid plaque scores were calculated by summing the degrees of stenosis measured at all locations. RESULTS: LVH was detected in 89 of the patients (75%). Plaque-positive patients had higher left ventricular mass index (LVMI) than plaque-negative patients (175+/-59 vs 143+/-46 g/m2, P = 0.003). LVMI was correlated with systolic blood pressure (r = 0.62, P<0.001), pulse pressure (r = 0.58, P<0.001), haemoglobin levels (r = - 0.25, P = 0.008), carotid plaque score (r = 0.32, P = 0.001) and coronary (CACS) and aortic wall calcification score (AWCS) (r = 0.34, P = 0.002 and r = 0.43, P<0.001, respectively). Multiple linear regression analysis (model r = 0.76) showed the independent factors related to LVMI to be systolic blood pressure, pulse pressure, CACS and presence of carotid plaques. CONCLUSION: Extra-coronary atherosclerosis and vascular calcification are associated with LVH in HD patients. Whether the treatment of atherosclerosis or vascular calcification may cause regression of or even prevent LVH in HD patients remains to be seen.     

Association of prohepcidin and hepcidin-25 with erythropoietin response and ferritin in hemodialysis patients

Hepcidin is a key regulator of iron metabolism. In this study, we examined whether measurement of hepcidin is useful in assessing recombinant human erythropoietin (rHuEPO) responsiveness in regular hemodialysis (HD) patients in a cross-sectional fashion. We examined the association between serum prohepcidin, a prohormone of hepcidin, and rHuEPO dosage and the rHuEPO/hemoglobin (Hb) ratio in 75 HD patients. We also semiquantatively measured the peak intensity of serum hepcidin-25, the major form of mature hepcidin, in 24 HD patients by using surface-enhanced laser desorption ionization time of flight time mass spectrometry, and compared those between rHuEPO-hyporesponsive (rHuEPO 192 +/- 10 [126-252] IU/kg/week, n = 15) and responsive patients (rHuEPO 40 +/- 9 [0-81] U/kg/week, n = 9). A significant but weak relationship was found between serum prohepcidin and rHuEPO dosage (r = 0.24, p < 0.05) and rHuEPO/Hb ratio (r = 0.22, p = 0.06). However, prohepcidin did not become an indicator of hematopoietic parameters by multiple regression analysis. Serum hepcidin-25 intensity was significantly and positively correlated with ferritin (r = 0.51, p < 0.01) but not with log-transformed C-reactive protein. There was no difference in the intensities of serum hepcidin-25 between rHuEPO-hyporesponsive and responsive patients (64 +/- 10 vs. 52 +/- 16 AU, p = NS). It follows from these findings that the assessment of serum hepcidin using currently available assays was not valid in predicting rHuEPO responsiveness in chronic HD patients.     

Clinical assessment of atherosclerotic parameters and cardiac function in chronic hemodialysis patients

Background/aim  

Atherosclerosis is evaluated by carotid mean intima-media thickness (mean IMT), pulse wave velocity (PWV), and the aortic calcification index (ACI). We have attempted to examine if these atherosclerotic parameters are associated with each other and which parameters are closely related to cardiac function in chronic HD patients.     

Increased visfatin in hemodialysis patients is associated with decreased demands for recombinant human erythropoietin

Abstract

Background: Studies detected an association between visfatin and markers of iron metabolism in patients with insulin resistance. In this study, such a relation was evaluated in hemodialysis (HD) patients. Also relations between visfatin and hepcidin, demands for recombinant human erythropoietin (rHuEpo), inflammation, and situations characterized by insulin resistance were evaluated. Methods: After a four-week washout period from iron treatment, 33 HD patients and 20 healthy volunteers enrolled in the study. Serum visfatin, hepcidin, and interleukin-6 (IL-6) were assessed by means of enzyme-linked immunosorbent assay. Hemoglobin, serum iron, ferritin, and transferrin saturation (TSAT) were also measured. Results: Visfatin was markedly increased in HD patients. Visfatin levels did not differ between diabetics and non-diabetics. No relation was detected between visfatin and body mass index or IL-6 in HD patients. From the markers of iron metabolism, the hepcidin included, visfatin was related only to TSAT. A strong positive relation was revealed between visfatin and hemoglobin, whereas visfatin was inversely related to rHuEpo dose. Resistance to rHuEpo index was inversely and independently of TSAT related to visfatin. Conclusion: Visfatin is increased in HD patients and it is associated with decreased demands for rHuEpo.     

慢性肾衰竭患者血清骨保护素浓度与心脏瓣膜钙化的关系

目的探讨慢性肾衰竭（CRF）患者血清骨保护素（OPG）水平与心脏瓣膜钙化的关系。方法以75例CRF患者[非透析组（ND）25例,腹透组（PD）28例,血透组（HD）22例1和10例健康人（对照组）为研究对象,采用酶联免疫复合物法测定患者血清OPG水平,分析其与心脏瓣膜钙化之间的关系。结果各组CRF患者血清中OPG水平[ND组（4.77±1.74）μg/L、PD组（5.22±1.57）μg/L、HD组（5.35±1.72）μg/L]显著高于对照组[（2.04±0.57）μg/L,P〈0.01]。OPG水平与年龄（r=0.311,P〈0.05）和C反应蛋白水平（r=0.353,P〈0.01）呈正相关。根据有无心脏瓣膜钙化分组后发现,存在瓣膜钙化的CRF患者OPG水平较无瓣膜钙化组显著升高[（6.28±1.66）μg/L比（4.59±1.40）μg/L,P〈0.01]。Logistic回归分析显示血清OPG水平是CRF患者心脏瓣膜钙化发生的一项独立危险因素（P〈0.01）。结论在CRF患者中,血清OPG水平与心脏瓣膜钙化相关。     

The Relationship of Visfatin Levels to Inflammatory Cytokines and Left Ventricular Hypertrophy in Hemodialysis and Continuous Ambulatory Peritoneal Dialysis Patients

Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-α, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-α levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 ± 387.86 ng/mL) than hemodialysis (97.68 ± 244.96 ng/mL,) and control (41.33 ± 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-α (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = ?0.305, p = 0.01), (r = ?0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (β = 0.369, p = 0.001) and IL-6 (β = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-α. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index.     

An association between inflammatory state and left ventricular hypertrophy in hemodialysis patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1beta, IL-6, TNF-alpha, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r=0.556, p=0.001), diastolic BP (r=0.474, p=0.004), and serum levels of TNF-alpha (r=0.446, p=0.009). Multiple regression analysis showed that systolic BP and TNF-alpha levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 +/- 8.7 vs. 7.3 +/- 0.7 pg/ mL, p=0.001). Predialysis serum levels of TNF-alpha in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 +/- 3 vs. 7 +/- 1.45 pg/mL, respectively, p>0.05). However, serum levels of IL-6 and TNF-alpha significantly elevated after HD, when compared to predialysis levels (from 15.7 +/- 8.7 to 17.8 +/- 9.5 pg/mL, p=0.001 and from 8.3 +/- 3.0 to 9.9 +/- 3.5 pg/mL p=0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-alpha in particular, seem to be associated with LVH in ESRD patients.     

The Relationship Between Leptin Level and Oxidative Status Parameters in Hemodialysis Patients

Both serum leptin level and oxidative stress are increased in hemodialysis (HD) patients. In the present study, we aimed to investigate whether there is association between oxidative status and leptin level in HD patients. Thirty-five HD patients and 25 healthy controls were enrolled in the present study. Serum leptin level, total peroxide (TP) level, total antioxidant capacity (TAC), and oxidative stress index (OSI) were determined. Serum leptin level, TP level, and OSI were significantly higher in HD patients than controls (all P  < 0.001) while TAC was lower ( P  < 0.001). In HD patients, serum leptin level was significantly correlated with TP level and OSI ( r  = 0.372, P  <  0.001 and r  = 0.409, P  < 0.001, respectively). The correlation of serum leptin level with TP level and OSI remained statistically significant after adjusting for age, gender, and body-fat percentage ( r  = 0.446, P  < 0.001 and r  = 0.463, P  < 0.001, respectively). Hyperleptinemia seems to be associated with increased oxidative stress in HD patients, and this association may provide better understanding about the disorders related to either elevated serum leptin levels and/or increased oxidative stress in HD patients.     

维持性血液透析患者缺血修饰白蛋白水平与腹主动脉钙化相关性分析

目的 研究维持性血液透析(maintenance hemodialysis,MHD)患者中缺血修饰白蛋白(ischemia-modified albumin,IMA)水平及其相关因素,并分析IMA与腹主动脉钙化(ab-dominal aortic calcification,AAC)的关系.方法 选取2016年1月至2...     

Warfarin and aortic valve calcification in hemodialysis patients

BACKGROUND: This retrospective cohort study was designed to determine the association between long-term exposure to warfarin and severity of aortic valve (AV) calcification in hemodialysis (HD) patients. METHODS: One hundred and eight HD patients underwent a study-specific echocardiogram. A grading scheme was used to classify AV calcification as none, mild, moderate and severe. Demographic, biochemical and medication data were abstracted by chart review. RESULTS: One hundred and eight subjects were enrolled. A minority had no calcification (n=17, 15.7%), the majority had mild calcification (n=62, 57.4%), and fewer had calcification rated as moderate (n=16, 14.8%) or severe (n=13, 12%). Dialysis vintage was associated with severity of AV calcification (p=0.04). The 18 subjects with long-term warfarin exposure (36.7 +/- 19.7 months) were more likely to have severe AV calcification (p=0.04). The odds ratio of falling into a higher category of AV calcification following 18 months of warfarin was 3.77 (95% confidence ratio, 0.97-14.70; p=0.055). There was an association between lifetime months of warfarin exposure and severity of AV calcification (p=0.004) that was independent of dialysis vintage, calcium and calcitriol intake. CONCLUSIONS: The data suggest that warfarin may be associated with severity of AV calcification in HD patients and support the need for prospective studies.     

Measurement of des-gamma-carboxy prothrombin levels in hemodialysis patients positive for anti-hepatitis virus C antibody

BACKGROUND: The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-gamma-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II. PATIENTS AND METHODS: Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 +/- 11 years, duration of HD: 17 +/- 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and alpha-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters. RESULTS: Serum PIVKA-II became positive (> or = 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), gamma-GTP (r = 0.21, p < 0.01) and platelet counts (r = -0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = -0.72, p = 0.01). CONCLUSION: The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.