Oxidative stress and high-density lipoprotein function in Type I diabetes and end-stage renal disease

In a cross-sectional study, oxidative stress in high vascular disease risk groups, ESRD (end-stage renal disease) and Type I diabetes, was assessed by measuring plasma protein carbonyls and comparing antioxidant capacity of HDL (high-density lipoprotein) as pertaining to PON1 (paraoxonase 1) activity and in vitro removal of LPO (lipid peroxides). ESRD subjects on haemodialysis (n=22), Type I diabetes subjects (n=20) without vascular complications and healthy subjects (n=23) were compared. Plasma protein carbonyls were higher in ESRD patients [0.16 (0.050) nmol/mg of protein; P=0.001; value is mean (SD)] relative to subjects with Type I diabetes [0.099 (0.014) nmol/mg of protein] and healthy subjects [0.093 (0.014) nmol/mg of protein]. Plasma PON1 activity, with and without correction for HDL-cholesterol, was lower in diabetes but did not differ in ESRD compared with healthy subjects. Plasma PON1 activity, without correction for HDL, did not differ between the three groups. In ESRD, plasma PON1 activity and plasma protein carbonyl concentrations were inversely related (r=-0.50, P<0.05). In an in vitro assay, LPO removal by HDL in ESRD subjects was greater than HDL from healthy subjects (P<0.01), whereas HDL from patients with Type I diabetes was less effective (P<0.01). Efficacy of LPO removal was unrelated to plasma PON1 activity, in vitro glycation or mild oxidation, but was impaired by marked oxidation and glycoxidation. Protein carbonyl levels are increased in ESRD but not in complication-free Type I diabetes. HDL antioxidant function is increased in ESRD, perhaps a compensatory response to increased oxidative stress, but is lower in Type I diabetes. HDL dysfunction is related to glycoxidation rather than glycation or PON1 activity.     

Correlation between ischaemia-modified albumin and intermediate-density lipoprotein in haemodialysis patients with end-stage renal disease

This study investigated the association between ischaemia-modified albumin (IMA), a biomarker of cardiac ischaemia, and increases in the levels of intermediate-density lipoprotein (IDL), an atherogenic particle that can cause oxidative stress, in haemodialysis patients with end-stage renal disease (ESRD). Fasting levels of serum IMA and lipids/lipoproteins were analysed in 15 patients and 15 healthy control subjects. There was a close positive correlation between IMA and IDL levels in ESRD patients but no significant correlation between IMA and lipids/lipoproteins in control subjects. This suggests a possible link between the characteristic dyslipoproteinaemia found in ESRD and levels of IMA and, if confirmed in studies with larger sample sizes, may lead to further studies on the potential of the relationship between IMA and IDL as a biomarker in haemodialysis patients with ESRD.     

影响胸段食管癌切除术后的预后因素的Cox模型分析

目的:探讨影响胸段食管癌切除术后患者的预后因素.方法:对217例经"三野"淋巴结清除根治术的食管癌患者的临床资料进行回顾性分析.选择9个可能对食管癌切除术后预后产生影响的特征性临床病理因素,通过计算机Cox比例风险模型进行预后分析.结果:全组淋巴结清除术后1、3、5年生存率分别为82.6%、59.8%和48.8%.影响预后的单因素分析表明肿瘤浸润深度、分化程度、临床分期、淋巴结转移个数、淋巴结转移区域数、年龄对预后有影响,而性别、肿瘤长度和肿瘤部位与预后无关.影响预后的Cox模型多因素分析表明,肿瘤浸润深度、分化程度、淋巴结转移区域数和肿瘤部位对预后有显著的影响.随着食管癌淋巴结转移区域数的增加,患者生存率逐渐下降(P=0.0284).结论:淋巴结转移尤其是淋巴结转移区域数是胸段食管癌切除术后影响患者预后的主要因素,应常规行"三野"淋巴结清扫术,以提高患者5年生存率.     

Breath analysis in patients with end-stage renal disease: effect of haemodialysis

Background There is no agreement about exhaled nitric oxide (FE_NO) and its change after haemodialysis (HD) in end‐stage renal disease (ESRD) patients. To comprehensively assess NO production in the respiratory system, NO metabolites in exhaled breath condensate (EBC) needs to be measured in addition to FE_NO, taking into account the influence on these markers of airway pH, which may be regulated by ammonia (), present in large amounts in the breath of ESRD patients and removed by HD. Study design FE_NO and NO metabolites (NOx, , ), pH and in EBC were measured in 12 ESRD patients, before and after HD. Twelve healthy subjects acted as controls. Results FE_NO values of ESRD patients were similar to normals, while EBC‐NOx, , and pH were significantly higher in ESRD patients compared to normals (EBC‐NOx 12·3, range 11·1–41·9 µm vs. 9·4, range 4·6–10·9 µm , P = 0·007; 4·70, range 1·17–8·22 µm vs. 0·90, range 0·72–1·17 µm , P = 0·023; 2340, range 1325–3922 µm vs. 660, range 406–872 µm , P < 0·001; pH 7·16, range 6·82–7·44 vs. 6·60, range 6·42–6·76, P = 0·004, respectively). HD caused a mild significant decrease of FE_NO, and normalization of , NOx, and pH. A significant positive relationship between EBC‐pH and EBC‐ before and after HD (r² = 0·65, P = 0·000) was observed, explaining higher than normal EBC‐pH before HD, while no relationship was found between EBC‐pH and FE_NO or NO metabolites. Conclusion Oxidative stress, and not EBC‐pH, is the most probable cause of increased NO metabolites in ESRD patients before HD.     

Klotho基因多态性与终末期肾病及继发性甲状旁腺功能亢进的相关性

目的观察klotho基因G-395A多态性与终末期肾病(ESRD)及继发性甲状旁腺功能亢进(SHPT)发病风险的相关性。方法选取2015年4月至2016年12月期间就诊于苏北人民医院肾内科及扬州市四区县血液净化中心的ESRD患者200例,体检中心正常体检者80名为对照组,运用FQ-PCR(Taqman法)对各研究对象进行Klotho基因G-395A多态性分型,检测SHPT相关指标:钙(Ca)、磷(P)、全段甲状旁腺激素(i PTH);比较各组间基因分型、等位基因频率,分析不同基因亚型与SHPT的相关性因素。结果研究人群Klotho基因G-395A位点分布符合HardyWeinberg平衡(P>0.05);ESRD组GA+AA基因型频率高于对照组(P<0.05);ESRD组患者A等位基因频率为34.75%,对照组A等位基因频率为23.12%,两者比较差异有统计学意义(P<0.05);重度SHPT患者GA+AA基因频率高于轻度SHPT患者(P<0.05);重度SHPT患者A等位基因频率为47.73%,轻度SHPT患者A等位基因频率为29.91%,两者比较差异有统计学意义(P<0.05);ESRD组不同基因型间钙磷及PTH指标差异无统计学意义(P>0.05)。结论研究人群中存在Klotho基因G-395A多态性Klotho基因G-395A位点A等位基因可能是发生ESRD遗传易感基因Klotho基因G-395A位点A等位基因可能是发生重度SHPT遗传易感基因。     

Pharmacokinetics of rosiglitazone in patients with end-stage renal disease

The pharmacokinetics and tolerability of a single 8-mg oral dose of rosiglitazone, an anti-diabetic agent, were compared in 10 long-term haemodialysis patients and 10 healthy volunteers. Haemodialysis patients received rosiglitazone 4 h after haemodialysis (non-dialysis day) and 3 h before haemodialysis (dialysis day). Haemodialysis did not influence rosiglitazone pharmacokinetics, and dialytic clearance was low (0.10 1/h). The mean area under the concentration-time curve (AUC(0-infinity)), the maximum observed plasma concentration (Cmax) and the half-life for rosiglitazone were similar in haemodialysis patients (non-dialysis day) and healthy individuals (2192 +/- 598 ng.h/ml versus 2388 +/- 494 ng.h/ml, 338 +/- 114 ng/ml versus 373 +/- 95 ng/ml, and 3.70 +/- 0.75 h versus 3.81 +/- 0.86 h, respectively). AUC(0-infinity) and Cmax were not markedly influenced by haemodialysis. Rosiglitazone dose adjustments are not warranted in patients with type 2 diabetes with end-stage renal failure on haemodialysis.     

Functional status of patients with end-stage renal disease

A longitudinal study of 979 patients with end-stage renal disease from 27 dialysis centers in the Upper Midwest was conducted to measure the patients' functional status with use of the Karnofsky Activity Scale. At the initiation of dialysis, 50% of all patients were rehabilitated or caring for themselves, and the three variables that most influenced the initial rehabilitation score were age, diabetic status, and sex. Initial functional status was also analyzed for three cohorts of dialysis patients, grouped according to outcome (renal transplantation, continued dialysis, and death). Patients who received a renal transplant had initial rehabilitation scores that were higher than those who underwent dialysis for 2 years or those who died. In the group of patients who underwent dialysis for 2 years, a statistically significant improvement in rehabilitation scores was noted at 2 years in comparison with the scores obtained at the initiation of dialysis. Initial rehabilitation scores were good predictors of the 2-year scores. Of the patients in the 2-year dialysis cohort, 78% maintained or had improvement in their functional status.     

终末期肾脏疾病患者透析治疗的相关因素分析

目的:回顾性分析终末期肾脏疾病透析患者病因、年龄、性别与选择血液透析和全部腹膜透析的关系。方法:收集2003-01/2004-05中南大学湘雅二医院病案统计室、血液净化中心及腹透中心终末期肾脏疾病透析患者资料356例,血液透析患者307例,全部腹膜透析患者49例。血液透析患者采用日本东丽公司,美国百特公司,德国费森-尤斯公司和贝朗公司的血液透析机,采用双醋酸纤维膜、血仿膜和合成膜;空心纤维透析器,透析液为碳酸氢盐透析液,采用肝素(普通肝素或低分子肝素)抗凝,透析时血流量为200～280mL/min,透析液流量为500mL/min,患者透析频率及时间为每周两三次,每次4～4.5h。全部腹膜透析患者采用解剖法置入腹膜透析导管,腹膜透析方法为持续不卧床腹膜透析,腹膜透析外管连接方式为美国百特公司双联系统,腹膜透析液使用含葡萄糖的透析液。分别记录患者姓名、性别、年龄、原发疾病、血尿素氮,肌酐(取患者第一次透析前清晨空腹采血所测数值)、透析的方式等资料,进行统计和分析,分析其病因及其与年龄、性别、透析方式选择的关系。结果:透析患者356例全部进入结果分析。①终末期肾脏疾病透析患者主要病因为慢性肾小球肾炎(52.0%),其次为糖尿病肾病(16.0%),高血压肾病(13.2%),梗阻性肾病(9.0%);男女之比为1.87∶1,平均年龄为(51±16)岁。②腹膜透析患者的平均年龄明显高于血液透析患者[(59±15),(50±16)岁,P<0.05]。86.2%的患者选择血液透析,13.4%选择腹膜透析;糖尿病肾病患者选择腹腹膜透析高于血液透析(P<0.01)。③结缔组织病、慢性肾小球肾炎组患者年龄较小,狼疮平均年龄仅40岁;高血压肾病、糖尿病肾病、梗阻性肾病、痛风、多发性骨髓瘤患者年龄较大,40岁以上患者约95.0%,平均年龄约60岁,与慢性肾炎、狼疮比较,差异有显著性意义(P<0.05)。结论:本组患者以中老年为主,男性多见;终末期肾脏疾病透析患者主要病因为慢性肾小球肾炎,其次为糖尿病肾病;糖尿病肾病首选腹膜透析。     

Psychotropic medication in the patients with end-stage renal disease

The majority of psychotropic drugs are well tolerated in the patients with end-stage renal disease. There are exceptions for which tolerance and safety are questionable. These include psychotropic drugs such as milnacipran, sulpiride, lithium carbonate, memantine, gabapentin, pregabalin and topiramate.     

Reproducibility of exercise tolerance in patients with end-stage renal disease

OBJECTIVE: To determine the interday reproducibility of peak and submaximal exercise tolerance of patients with end-stage renal disease (ESRD). DESIGN: Repeated measures. SETTING: Day-patient rehabilitation center. PARTICIPANTS: Twelve consecutively presenting, self-selected patients with ESRD. INTERVENTIONS: All patients performed peak exercise tolerance assessments on a cycle ergometer up to the point of volitional fatigue, with a 1-week interval between the 2 tests. MAIN OUTCOME MEASURES: Cardiopulmonary, hemodynamic, and physical performance parameters were assessed at peak exercise and at the lactate threshold. Standard error of measurement, percentage coefficient of variation (CV%), intraclass correlation coefficient (ICC), and limits of agreement (LOA) were calculated to determine the reproducibility of all variables. RESULTS: CV% (range, 5%-7%) and ICCs (range, .94 - .98) for oxygen uptake and heart rate at peak exercise and lactate threshold indicated highly acceptable levels of group mean reproducibility. LOA analysis revealed satisfactory levels of reproducibility for individual patients. CONCLUSION: Taken together, these reproducibility data may be applied to clinical work, requiring the quantification of changes in the exercise tolerance of patients with ESRD after short-term interventions (eg, exercise training, therapeutic use of recombinant erythropoietin).     

Survival rates of 2,728 patients with end-stage renal disease

This multicenter regional study analyzes survival of a large group of patients who began chronic dialysis or received their first renal transplant during the 5 1/2-year period that ended in June 1983. Survival was determined from the onset of renal replacement therapy, irrespective of changes in treatment modality. Univariate life-table analysis was used to examine more than 35 risk factors. Age of patients at entry into the therapeutic program significantly affected survival. General survival rates were lower for patients with diabetes than for nondiabetics, irrespective of treatment modality, with the exception of those older than 60 years of age. Five-year graft survival was lower for diabetics than for nondiabetics in all age groups, irrespective of source. Patients with systemic lupus erythematosus, focal glomerulosclerosis, or glomerulonephritis had the highest survival rates, whereas those with primary renal malignant lesions, primary hypertensive disease, or diabetes mellitus as the cause of renal failure had the lowest. Concurrent morbid conditions that adversely affected survival included arteriosclerotic heart disease, peripheral vascular disease, noncutaneous malignant lesions, chronic pulmonary disease, and multiple coexisting morbid conditions. Although the objective of this study was to analyze survival for single patient characteristics, irrespective of treatment modality, analyses of survival rates by treatment modality for a control group indicated that minimal differences were evident by the third year among the four treatment groups: in-center hemodialysis, home hemodialysis, living related donor transplantation, and cadaver transplantation; however, recipients of cadaver grafts had lower survival rates than all other groups, even those maintained by in-center hemodialysis (P = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)     

终末期肾病患者的心理状态

在治疗患者身体疾病的同时关注其心理健康,改善其生活质量是治疗终末期肾病(ESRD)患者的理想目标[1],然而,对于一些尿毒症患者及透析患者这种目标却远未实现.     

25例高转换型肾性骨病的骨组织学研究

目的通过对慢性肾脏病(chronic kidney disease,CKD)5期维持性血液透析(maintenance hemodialysis,MHD)患者行骨活检获得骨标本,对骨病理进行骨形态计量学分析,观察各型骨病尤其是高转换型肾性骨病的骨病理学特点并探讨临床各项常用无创性检查的意义。方法选择40例CKD5期MHD患者和3例正常人进行髂骨活检术,获得骨标本。采用全自动图像分析系统进行骨组织形态计量学测定。外周血各项检测指标和临床常用的骨密度和骨骼摄片与骨病理学指标行相关分析。结果25例CKD5期MHD患者经骨病理学检查证实为高转换型骨病,占同期骨活检的62.5%(25/40),骨病理学检查以破骨细胞活化形成骨吸收陷窝伴或不伴骨矿化不全为特点。外周血钙、骨钙素水平与骨病理指标呈显著正相关。骨密度和骨骼摄片的阳性率低于骨活检。结论通过对CKD5期MHD患者行骨活检发现,高转换性肾性骨病的比例仍占大多数。在高转换型肾性骨病中,目前的各种无创性检查中血钙、骨钙素可能具有一定的预测价值。骨活检仍是诊断肾性骨病的金指标。     

影响肝细胞癌根治性切除术后预后因素的Cox模型分析

目的探讨影响肝细胞癌根治性切除术后预后的相关因素，为肝细胞癌的术后综合治疗及判断预后提供依据。方法回顾性分析194例肝细胞癌的临床病理资料，对潜在的可能影响术后预后的临床病理因素进行单因素分析，将单因素分析后有统计学意义的因素带人Cox比例风险回归模型进行多因素分析。结果全组患者的术后1、3、5年的累积生存率分别为81．4％、50．6％、33．9％。单因素分析结果显示：术前AST、ALP、GGT、肿瘤最大直径、肿瘤病灶数目、手术持续时间、手术中总失血量、手术中输血情况、术后2年内复发是有统计学意义的因素。Cox模型多因素分析结果示术后2年内复发、术前AST浓度是有统计学意义的因素。结论HCC根治性切除术后的预后取决于多种因素的共同作用，术后2年内复发、术前AST浓度是影响术后预后的最重要因素。     

Cost-effectiveness analysis of end-stage renal disease treatments

The cost-effectiveness of various end-stage renal disease (ESRD) treatments was compared using two different cost measures. The first measure, gross social costs, excluded output gains due to treatment, whereas the second measure, net social costs, included output gains from both market and nonmarket activities. The cost-effectiveness criterion was the cost-per-life year gained or the implicit value of a year of life. The lower the cost-per-life year gained, the more cost-effective the treatment was. Four ERSD treatments were evaluated over 20 years. Home dialysis and transplantation were more cost-effective than in-center dialysis, regardless of whether gross or net social costs were used. However, lower values were obtained in the case of net social costs reflecting a provision for output gains due to treatment. The use of net social costs also resulted in greater variations in costs-per-life year gained by age. Changes in survival probabilities affected the results for transplant patients and dialysis patients differently.     

Exercise capacity in pediatric patients with end-stage renal disease.

OBJECTIVE: To evaluate the correlation between exercise capacity and hemoglobin in pediatric patients with end-stage renal disease (ESRD) treated with automated peritoneal dialysis (APD) and hemodialysis. DESIGN: Prospective case-control study and retrospective review. SETTING: Dialysis summer camp and Children's Mercy Hospital exercise laboratory. PARTICIPANTS: Prospective evaluation conducted with 14 patients (9 males, mean age 14.5 +/- 2.5 years) who received either home APD (5 patients) or in-center hemodialysis (9 patients), and 8 healthy age-matched controls. Retrospective data derived from 10 children (7 males, mean age 12.3 +/- 3.3 years), all of whom received APD. INTERVENTION: Maximal treadmill evaluation conducted with each patient and control. The hemoglobin value of each patient was also assessed. MAIN OUTCOME MEASURES: Comparison of the following data generated during treadmill protocol: peak heart rate, blood pressure, oxygen saturation, treadmill time, oxygen consumption (VO2), ventilation (Ve), oxygen consumption at anaerobic threshold (VO2AT), and respiratory exchange ratio. RESULTS: The hemoglobin value of the current patient group (12.8 +/- 1.6 g/dL) was significantly greater than the previously studied patients (10.5 +/- 1.1 g/dL) (p = 0.001). Treadmill time, VO2, and VO2AT were significantly lower in both groups of dialysis patients compared to the control subjects (p < 0.05). No differences were noted in any of these variables when comparing these two groups of dialysis patients only. CONCLUSION: The exercise capacity of pediatric dialysis patients is significantly poorer than that of healthy children, an outcome apparently related to factors other than normalization of the hemoglobin value.     

Impaired resistance artery function in patients with end-stage renal disease

We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈?200?μm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls. NO (nitric oxide) contribution to flow was lacking in ESRD patients, but present in the controls. ADMA (asymmetrical dimethyl L-arginine) levels were higher in the ESRD group compared with the control group. Dilatation in response to acetylcholine was reduced in ESRD patients compared with controls, but response to NO donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased in arteries from ESRD patients compared with controls. Arterial remodelling was absent in ESRD patients. There was no difference between the groups in myogenic tone, vascular reactivity or sensitivity to several vasoconstrictors. Arterial distensibility, reflecting passive properties of the vascular wall, was reduced in ESRD patients compared with controls. Exclusion of ESRD patients with diabetes and/or cardiovascular disease from analyses had no influence on the main findings. Thus we propose that uraemia has a strong impact on endothelial function and passive properties of the arterial wall of human peripheral resistance vasculature. The reduced contribution of NO to flow stimulus via enhanced nitrosative stress and higher plasma concentrations of ADMA may suggest potential mechanisms behind endothelial dysfunction in the resistance peripheral circulation in ESRD.