首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到10条相似文献,搜索用时 125 毫秒
1.
Impaired endothelium-dependent vasodilatation in renal failure in humans.   总被引:4,自引:4,他引:0  
BACKGROUND: The main causes of death in patients with chronic renal failure (CRF) are cardiovascular complications. The aim of the present study was to compare endothelium-dependent vasodilatation (EDV) in patients with chronic renal failure with a control population controlling for hypertension, diabetes mellitus and hypercholesterolaemia. METHODS: Fifty-six patients with moderate CRF (mean creatinine clearance 29.4 ml/min/1.73 m(2)) underwent evaluation of EDV and endothelium-independent vasodilatation (EIDV) by means of forearm blood flow (FBF) measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (Mch, 2 and 4 microg/min evaluating EDV) and sodium nitroprusside (SNP, 5 and 10 microg/min evaluating EIDV). Fifty-six control subjects without renal impairment underwent the same investigation. RESULTS: Infusion of Mch increased FBF significantly less in patients with renal failure than in controls (198 vs 374%, P<0.001), whereas no significant difference was seen regarding the vasodilatation induced by SNP (278 vs 269%). The differences in EDV between the groups were still significant after controlling for hypertension, blood glucose, and serum cholesterol in multiple regression analysis (P<0.001). EDV was related to serum creatinine (r=-0.37, P<0.01), creatinine clearance (r=0.45, P<0.005) and to serum triglyceride levels (r=-0.29, P<0.005) in the CRF group. CONCLUSIONS: Patients with moderate CRF have an impaired EDV even after correction for traditional cardiovascular risk factors and this impairment is related to the degree of renal failure.  相似文献   

2.
Oxidized LDL (oxLDL) is a key mediator in atherogenesis and a marker of coronary artery disease (CAD). Type 2 diabetes is associated with excessive cardiovascular morbidity and mortality. Because atherogenesis starts before diabetes is diagnosed, we investigated whether circulating oxLDL levels are increased in impaired glucose tolerance (IGT). OxLDL levels were measured in 376 subjects with normal glucose tolerance (NGT), 113 patients with IGT, and 54 patients with newly diagnosed type 2 diabetes. After correction for age and BMI, serum levels of oxLDL were significantly increased in IGT versus NGT subjects (P = 0.002). OxLDL levels were not associated with the following parameters of the oxidative/antioxidative balance in the blood: total antioxidant capacity, urate-to-allantoin ratio, and circulating phagocyte oxygenation activity. In stepwise multivariate analysis, LDL cholesterol (P < 0.0005) and triglycerides (P < 0.0005) were the strongest predictors of circulating oxLDL levels, followed by HDL cholesterol (P = 0.003), 2-h postchallenge C-peptide (P = 0.011), fasting free fatty acids (P = 0.013), and serum paraoxonase activity (P = 0.035). The strong correlation of oxLDL with LDL cholesterol and triglycerides indicates that LDL oxidation in IGT is preferentially associated with dyslipidemia. OxLDL increase may explain the high atherogenic potency of dyslipidemia in the prediabetic state.  相似文献   

3.
BACKGROUND: Cardiovascular disease (CVD) is a frequent complication in chronic haemodialysis (HD) patients. Endothelial dysfunction, as measured by soluble cellular adhesion molecules (sCAM) and von Willebrand factor (vWf) in plasma, is an early manifestation of CVD. Today, it is unknown if, and to what extent, their levels are influenced by the type of dialyser. METHODS: Four dialysers, low-flux cuprammonium (CU); high-flux and low-flux polysulfone and super-flux polyethersulfone, were compared in 15 chronic HD patients in a randomized cross-over fashion. sCAM and vWf were measured at baseline as well as after 4 weeks, and both intra-dialytical and after 24 h (t24 h). Twenty healthy subjects served as controls. RESULTS: Baseline levels were considerably higher in chronic HD patients than in controls (soluble intercellular adhesion molecule-1: sICAM-1 732+/-216 vs 572+/-259 ng/ml, P = 0.06; soluble vascular cell adhesion molecule-1: sVCAM-1 1917+/-492 vs 1126+/-338 ng/ml, P<0.001; vWF: 205+/-55% vs 98+/-52%, P<0.001). After 4 weeks, no changes were observed. During and after HD, sCAM did not change, except in the case of CU (sICAM-1: 719+/-259 to 772+/-261 ng/ml, P = 0.04). CU induced a rise in vWF directly after HD (t4 h; from 188+/-48% to 255+/-92%, P<0.01), whereas all modalities induced a significant increase at t24 h (mean 228+/-54%, P = 0.02). The levels of sCAM and vWf appeared to be dependent on the individual patients rather than on the type of dialyser (explained variance by different patients: 66%-91%, P<0.001; by type of dialyser 0.4-1.2%). CONCLUSIONS: Baseline levels of sCAM and vWf were markedly higher in chronic HD patients than in controls and did not change after 4 weeks with any dialyser. All membranes induced a marked rise in vWf at t24 h, whereas sICAM-1 increased only in the case of CU at t4 h. As sCAM showed no marked changes during HD with any other modality, our study suggests activation of blood cells rather than endothelial cells. As pre-dialysis levels of sCAM and vWf varied noticeably between individual patients, endothelial dysfunction seems to be far more dependent on patient-related factors than on the HD treatment itself.  相似文献   

4.
INTRODUCTION: Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients. OBJECTIVE: The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients. METHODS: We studied a group of 12 recipients (6 men and 6 women of mean age 55 +/- 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoA1, ApoB, and Lp(a) levels. RESULTS: The change to tacrolimus resulted in significant decreases in TC levels, 213 +/- 30 (B) versus 185 +/- 27 (12s) (P < .01); LDL, 129 +/- 24 (B) versus 104 +/- 14 (12s) (P = .002); and ApoB 98 +/- 15 (B) versus 85 +/- 10 (12s) (P < .01). HDL levels significantly increased (45 +/- 10 vs 48 +/- 10 [12s]; P = .018), whereas oxLDL concentrations decreased significantly after conversion (B) (55.42 +/- 10.61 vs 12s 45.76 +/- 10.21; P < .01). Converting to tacrolimus produced a nonsignificant decrease in Ab-oxLDL (baseline 204.88 +/- 134.49 vs 12s 179.51 +/- 143.54). A correlation was observed between LDL and oxLDL (r = 65, P = .02 [B] and r = 0.7, P = .01 [12s]) but not between oxLDL levels and Ab-oxLDL concentration (r = -0.05, P = .87 [3] and r = -0.1, P = .77 [12s]). CONCLUSIONS: In renal transplantation, tacrolimus therapy was associated with a better lipid profile and lower in vivo LDL oxidation when compared with cyclosporine treatment.  相似文献   

5.
BACKGROUND: Heparin inhibits prothrombotic tissue factor (TF) and releases its inhibitor, tissue factor pathway inhibitor (TFPI), from the endothelium, but repeated administration of heparin depletes vascular stores of TFPI. We studied the anticoagulant effects of unfractionated heparin (UFH) vs low-molecular-weight enoxaparin-used for thrice-weekly maintenance haemodialysis (HD)-on plasma levels of total TF and TFPI and on those of an activated coagulation marker prothrombin fragment 1+2 (PF 1+2). METHODS: Twenty-five patients dialysed using a single injection of enoxaparin (at a mean dose of 0.68 mg/kg) were randomly assigned to either receive UFH administered as a mean bolus of 42.1 IU/kg and continuous infusion of 57.8 IU/kg (n=12) or to be maintained on enoxaparin (n=13), and were followed prospectively for 12 weeks. Plasma immunoreactive TF, TFPI and PF 1+2 were measured at the start and after 10 and 180 min of HD, and compared with values in 15 healthy controls. RESULTS: Pre-dialysis TF, TFPI and PF 1+2 were higher than normal (all P<0.0001). TF and PF 1+2 did not change, while TFPI levels, compared with baseline, increased at each interval in enoxaparin-anticoagulated HD patients (all P<0.0001). TFPI increments correlated inversely with pre-dialysis TFPI (both P<0.0007). In patients switched to UFH, TF levels remained unchanged compared with pre-randomization values, TFPI increased at each interval of HD sessions (all P<0.035) and PF 1+2 increased pre-dialysis (P=0.015). The over-dialysis effects of UFH resembled those of enoxaparin. In contrast, baseline TFPI and its 10-min rise correlated inversely with the UFH loading dose (both P<0.040). Pre-dialysis PF 1+2 was inversely associated with TFPI increments (both P<0.034), and directly with pre-dialysis TFPI (P=0.018) and the UFH loading dose (P=0.045). CONCLUSIONS: Depletion of heparin-releasable stores of TFPI is an untoward effect of repeated anticoagulation during maintenance HD therapy. The traditional UFH regimen is more prothrombotic than single enoxaparin injections, with high loading doses of UFH being involved in TFPI exhaustion and subsequent hypercoagulability.  相似文献   

6.
Oxidative stress and endothelial function in chronic renal failure.   总被引:19,自引:0,他引:19  
This study aimed to investigate the relationship between oxidative stress and endothelium-dependent vasodilation in patients with chronic renal failure (CRF). Thirty-seven patients with CRF underwent evaluation of endothelium-dependent vasodilation and endothelium-independent vasodilation by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (evaluating endothelium-dependent vasodilation) and sodium nitroprusside (evaluating endothelium-independent vasodilation). Lag phase of lipoprotein fraction to oxidation, total antioxidative activity, diene conjugates, thiobarbituric acid reactive substances, lipid hydroperoxide, reduced glutathione (GSH), oxidized GSH (GSSG), and the GSH redox ratio (GSSG/GSH) were all measured as markers of oxidative stress. Two groups of healthy subjects (61 and 37 subjects, respectively) were used as controls. In one group, oxidative stress markers were measured, whereas endothelium-dependent vasodilation and endothelium-independent vasodilation were assessed in the other group. Compared with controls, the patients with renal insufficiency had an impaired endothelium-dependent vasodilation, a shorter lag phase of lipoprotein fraction, and higher levels of diene conjugates, lipid hydroperoxide, and GSSG levels. The GSSG/GSH ratio was lower in patients with CRF. Endothelium-dependent vasodilation was positively correlated with total antioxidative activity (r = 0.41, P = 0.016), GSH (r = 0.44, P < 0.0098), and lag phase of LDL (r = 0.35, P = 0.036) and negatively correlated with GSSG (r = -0.40, P < 0.018), GSSG/GSH (r = -0.47, P = 0.0057), and diene conjugates (r = -0.53 P < 0.0015) in patients with CRF. These results show that an impaired endothelium vasodilation function and oxidative stress are related to each other in patients with CRF.  相似文献   

7.
BACKGROUND: Patients with end-stage renal disease (ESRD) as well as those with mild renal insufficiency are at increased risk for the development of cardiovascular disease, which cannot be attributed entirely to traditional risk factors. Endothelial dysfunction and chronic inflammatory activity, two important phenomena in atherogenesis, can be found in ESRD. At present, it is unclear whether endothelial dysfunction and chronic inflammatory activity are related to renal function in the pre-dialysis stage. METHODS: In a cross-sectional, single-centre study, four groups of 20 subjects with renal function ranging from a normal, calculated creatinine clearance (>90 ml/min) to a pre-dialysis situation (<31 ml/min) were investigated. We measured markers of endothelial function [von Willebrand factor (vWf), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and E-selectin (ES)], and markers of inflammatory activity [secretory phospholipase A(2) (sPLA(2)) and C-reactive protein (CRP)]. Using these markers, composite endothelial function and inflammatory activity scores were constructed. RESULTS: Creatinine clearance correlated with the endothelial function score (r=-0.43, P<0.001), the inflammatory activity score (r=-0.53, P<0.05), vWf (r=-0.54, P<0.001), sVCAM-1 (r=-0.50, P<0.001), sPLA(2) (r=-0.28, P<0.05), homocysteine (r=-0.61, P<0.001), age (r=-0.54, P<0.001) and blood pressure (r=-0.44, P<0.001). In multivariate analyses, creatinine clearance was an independent determinant of the endothelial function score (beta=-0.34, P=0.006), plasma vWf (beta=-0.37, P=0.022) and sICAM-1 (beta=-0.33, P=0.012). The relationship of creatinine clearance with sVCAM-1 and endothelial function score was not significant when plasma homocysteine was added to the model. Creatinine clearance was also a determinant of the inflammatory activity score (beta=-0.31, P=0.025) and sPLA(2) (beta=-0.32, P=0.024), although this was no longer significant after correction for systolic blood pressure. CONCLUSIONS: Renal dysfunction is associated with markers of endothelial dysfunction and inflammatory activity. Plasma homocysteine may be an intermediate factor in the relationship between endothelial dysfunction and renal function, while blood pressure may modulate the association between inflammatory activity and renal function.  相似文献   

8.
BACKGROUND: Some studies have demonstrated beneficial effects of L-arginine as a substrate for nitric oxide synthesis, and diclofenac as an inhibitor of cyclooxygenase (COX)-derived vasoconstrictive agents on vascular responses in humans during several pathological conditions. The aim of the present study was to investigate the acute effects of L-arginine and diclofenac on endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIDV) in patients with chronic renal failure (CRF). METHODS: Effects of L-arginine and diclofenac on EDV and EIDV were measured in 15 patients with CRF and in 15 healthy controls by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (2 and 4 micro g/min evaluating EDV) and sodium nitroprusside (5 and 10 micro g/min evaluating EIDV). RESULTS: L-Arginine infusion increased methacholine-induced vasodilatation both in patients with CRF and healthy controls. Diclofenac infusion increased methacholine-induced vasodilatation only in patients with CRF. There was no significant change in nitroprusside-induced vasodilatation after L-arginine and diclofenac infusions both in patients with CRF and healthy controls. CONCLUSIONS: These results suggest that COX inhibition reduces the levels of a prostanoid-derived vasoconstrictive agent contributing to the impaired EDV in patients with CRF, while in this age group L-arginine improves EDV regardless of renal function.  相似文献   

9.
BACKGROUND: Cardiovascular disease (CVD) is common in haemodialysis patients with chronic renal insufficiency and is the leading cause of death. The accelerated state of atherosclerosis found in these patients is due to a combination of different mechanisms. Recent studies confirm that inflammation plays an important role in the development of atherosclerosis. However, the role of hyperhomocysteinaemia and the immune response to oxidation of low-density lipoproteins (LDL) remains unclear and studies show contradictory results. The objective of this study was to determine whether there is a relationship between inflammation, hyperhomocysteinaemia and oxidative stress and whether these CVD risk factors are predictors of mortality in haemodialysis patients. METHODS: A prospective follow-up study was carried out in 94 stable, chronic haemodialysis patients for 24 months (July 1999-July 2001). All the patients were given folic acid and vitamin B complex supplements. Homocysteine was determined by fluorescence polarization immunoassay. C-reactive protein (CRP) levels were determined by chemiluminescent enzyme-labelled immunometric assay. Plasma copper oxidized anti-LDL (oxLDL) antibodies were measured by ELISA using native LDL and oxLDL as antigens. RESULTS: Thirty-two patients died during the study and 59.3% of the deaths could be attributed to CVD (eight to acute myocardial infarction and 11 to non-coronary vascular disease). The patients had slight hyperhomocysteinaemia (25.8 +/- 7.82 micromol/l), evidence of inflammation (CRP 5.16 mg/l (0.35-88.7)) and oxidative stress (oxLDL antibodies = 162 +/- 77 optical density at 495 nm x 1000). Age (P < 0.01), CRP (P = 0.03) and the oxLDL antibody titre (P < 0.01) were predictive of mortality. The patients who died from heart disease showed higher oxLDL antibody titres (P = 0.03). No correlation was found between homocysteine, CRP and the oxLDL antibody titre, or between serum homocysteine levels and the different causes of mortality. CONCLUSIONS: These results suggest that lipid peroxidation and inflammation, but not hyperhomocysteinaemia, are the main risk factors for mortality in haemodialysis patients receiving vitamin supplements. As the study was carried out in a relatively limited number of patients, our findings need to be confirmed in a larger patient population.  相似文献   

10.
BACKGROUND: Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. METHODS: One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. RESULTS: Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P < 0.0001) and a higher prevalence of carotid plaques (72 vs. 32%, P = 0.001). The prevalence of malnutrition (SGA 2 to 4) was 44%, and 32% of all patients had an acute-phase response (CRP > or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. CONCLUSION: These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号