Serum vascular adhesion protein-1 is increased in acute and chronic hyperglycemia

Background

The relationship between serum vascular adhesion protein-1 (VAP-1) and plasma glucose in normal and drug-naïve type 2 diabetes subjects is unclear. We examined if serum VAP-1 changed acutely to oral glucose loading and analyzed the relationship between serum VAP-1, fasting plasma glucose (FPG), hemoglobin A1c, and type 2 diabetes.

Methods

Adults without history of diabetes were included. Subjects taking anti-diabetic drugs were excluded. Serum VAP-1 was analyzed by time-resolved immunofluorometric assay.

Results

We recruited 333 subjects (186 females and 147 males), aged 56.1 ± 11.6 y. After glucose challenge, serum VAP-1 rose significantly at 30 min (p < 0.0001) and lasted until 2 h (p < 0.0001). The change of serum VAP-1 between fasting and 30-min postload correlated inversely to the change of plasma insulin (r = − 0.21, p = 0.049). Fasting serum VAP-1 was associated with FPG in those with FPG ≥ 5.55 mmol/l (p = 0.025) but not in those with FPG < 5.55 mmol/l (p = NS). Fasting serum VAP-1 were higher in diabetic subjects (p = 0.04) and correlated positively to hemoglobin A1c (r = 0.18, p = 0.002) after adjusting for age, gender, and waist circumference.

Conclusions

Serum VAP-1 is increased in both acute and chronic hyperglycemia. Whether serum VAP-1 is a good biomarker for hyperglycemia-associated complications merits further investigation.     

Glomerular filtration rate is an indicator of endothelial function at early stages of chronic kidney disease

AIM: To study effects of glomerular filtration rate (GFR) reduction on endothelial function in patients at early stages of chronic renal kidney (CKD). MATERIAL AND METHODS: Endothelial function of 101 patients with CKD of stage I-III was examined using reactive hyperemia test, dopplerography of skin vessels with ionophoresis of acetylcholin and nitroglycerin, lipidogram parameters, homocistein and annexin A5 levels, intima-media complex thickness of the common carotid artery, echocardiography findings. RESULTS: Cardiovascular complications risk factors were found in all the patients: increased body mass index, arterial hypertension, dyslipoproteinemia, hyperhomocysteinemia. Reduced GFR (under 90 ml/min) is an independent factor of atherosclerosis risk. CONCLUSION: GFR reduction corresponding to CRD of stage II is accompanied with enhancement of apoptosis and development of vasomotor endothelial dysfunction that in combination with risk factors contribute to development of a preclinical atherosclerosis phase.     

Dyslipidemia is a strong predictor of myocardial infarction in subjects with chronic kidney disease

Abstract

Aim. To evaluate dyslipidemia as predictor of myocardial infarction (MI) in subjects with or without chronic kidney disease (CKD). Methods. In 142,394 middle-aged Swedes referred for laboratory evaluation, glomerular filtration rates (GFR) were estimated using the Modification of Diet in Renal Disease study equation. CKD was defined as GFR 15–60 mL/min/1.73 m². Subjects were stratified into presence or absence of CKD, and lipid measures were related to MI using Cox's proportional hazards regression. Results. During 12 years of follow-up there were 5,466 MIs. The adjusted hazard ratio for MI for the highest versus the lowest quartile of the apolipoprotein (apo) B/apoA-1 ratio among individuals without CKD was 2.88 (95% confidence interval 2.54–3.26) and for those with CKD 3.35 (2.25–4.91). The corresponding estimates for the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio were 3.13 (2.78–3.52) and 3.54 (2.43–5.17), respectively. Receiver operator characteristics analyses showed an advantage in the prediction of MI for the apoB/apoA-1 ratio as compared to conventional lipids (P < 0.0001). Conclusions. The ratio of apoB/apoA-1, the ratio of total cholesterol/HDL cholesterol, and non-HDL cholesterol were all strong predictors of myocardial infarction, both among subjects with and without renal dysfunction, with a possible advantage for the apoB/apoA-1 ratio.     

可溶性血管黏附蛋白-1对2型糖尿病患者下肢大血管病变的影响

目的探讨2型糖尿病患者下肢血管病变时可溶性血管黏附蛋白-1(sVAP-1)和CRP的变化及其与2型糖尿病下肢血管病变的相关性。方法采用酶联免疫吸附法检测2型糖尿病患者64例及正常人20例的血清可溶性血管黏附蛋白-1、CPR水平,比较其差异,分析其意义。结果血清sVAP-1、CRP水平糖尿病组明显高于NC组,sVAP-1与糖尿病下肢血管病变相关。结论 sVAP-1是2型糖尿病下肢血管病变的危险因素。     

Serum tumour markers in patients with chronic kidney disease

Objective. Tumour markers are widely used for monitoring cancer patients and for screening certain tumours. It has recently been shown that the concentrations of some tumour markers are higher in patients with chronic kidney disease (CKD) than in healthy subjects. We analysed the influence of renal function and hemodialysis treatment on the serum levels of CA19‐9, CA125, alpha fetoprotein (AFP), CA15.3, CA72.4, CYFRA 21‐1, neuron‐specific enolase (NSE) and squamous cell carcinoma antigen (SCC‐Ag). Material and methods. 232 non‐dialysis patients with CKD and 37 uraemic patients treated with maintenance hemodialysis were enrolled in this study. The non‐dialysis patients were divided into three groups depending on their creatinine clearance (Ccr) levels: group 1 = Ccr ?25?mL/min; group 2 = 25.1–49.9?mL/min; group 3 = Ccr ?50?mL/min. For comparison, we chose 37 non‐dialysis patients with similar Ccr, age and same gender as controls. Results. The serum concentrations of CA19‐9, CA125 (male), CYFRA 21‐1, NSE and SCC‐Ag correlated negatively with Ccr, while there were no significant differences in the concentrations of CA125 (female), AFP, CA15.3, CA72.4. The serum levels of CA19‐9, CA125, AFP, CA15.3, CA72.4, CYFRA 21‐1, NSE and SCC‐Ag showed no differences between hemodialysis patients and non‐dialysis controls (p>0.017). Conclusions. The increase in the serum levels of CA19‐9, CA125 (in males), CYFRA 21‐1, NSE and SCC‐Ag in patients with CKD affects the specificity of these markers in the diagnosis of cancer. Hemodialysis does not affect the serum levels of CA19‐9, CA125, AFP, CA15.3, CA72.4, CYFRA 21‐1, NSE and SCC‐Ag.     

Wnt诱导信号通路蛋白1在肾脏疾病中应用的研究进展

Wnt诱导信号通路蛋白1是一种与炎症,损伤修复,肿瘤发生、发展等病理过程密切相关的蛋白,广泛参与了慢性肾脏病、赭曲霉毒素A相关性肾病、肾脏肿瘤等肾脏疾病的发病过程,有望成为诊断肾脏疾病的新型分子生物标志物及肾脏疾病治疗的靶点之一.本文就Wnt诱导信号通路蛋白1在肾脏疾病中应用的研究进展作一综述.     

Serum tumour markers in patients with chronic kidney disease

OBJECTIVE. Tumour markers are widely used for monitoring cancer patients and for screening certain tumours. It has recently been shown that the concentrations of some tumour markers are higher in patients with chronic kidney disease (CKD) than in healthy subjects. We analysed the influence of renal function and hemodialysis treatment on the serum levels of CA19-9, CA125, alpha fetoprotein (AFP), CA15.3, CA72.4, CYFRA 21-1, neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC-Ag). MATERIAL AND METHODS: 232 non-dialysis patients with CKD and 37 uraemic patients treated with maintenance hemodialysis were enrolled in this study. The nondialysis patients were divided into three groups depending on their creatinine clearance (Ccr) levels: group 1 = Ccr < or =25 mL/min; group 2 = 25.1-49.9 mL/min; group 3 = Ccr > or =50 mL/min. For comparison, we chose 37 non-dialysis patients with similar Ccr, age and same gender as controls. RESULTS: The serum concentrations of CA19-9, CA125 (male), CYFRA 21-1, NSE and SCC-Ag correlated negatively with Ccr, while there were no significant differences in the concentrations of CA125 (female), AFP, CA15.3, CA72.4. The serum levels of CA19-9, CA125, AFP, CA15.3, CA72.4, CYFRA 21-1, NSE and SCC-Ag showed no differences between hemodialysis patients and non-dialysis controls (p > 0.017). CONCLUSIONS: The increase in the serum levels of CA19-9, CA125 (in males), CYFRA 21-1, NSE and SCC-Ag in patients with CKD affects the specificity of these markers in the diagnosis of cancer. Hemodialysis does not affect the serum levels of CA19-9, CA125, AFP, CA15.3, CA72.4, CYFRA 21-1, NSE and SCC-Ag.     

The role of the primary care physician in managing early stages of chronic kidney disease

Recent increases in obesity, diabetes, and hypertension, along with the aging of the US population, are driving a dramatic rise in the prevalence of chronic kidney disease (CKD). Despite this increase, the majority of Americans with early-stage CKD remain unaware of their disease. Primary care physicians are at the forefront of efforts for early recognition of CKD and management to control its progression. Patients with CKD should be referred to nephrologists no later than the point at which their estimated glomerular filtration rate reaches 30 mL/min. Nephrology evaluation at this point is essential to facilitate timely preparation for care of end-stage renal disease through preemptive transplantation or planned transition to dialysis. In addition to stringent control of underlying hypertension and/or diabetes, mineral metabolic parameters (serum parathyroid hormone, phosphorus, calcium, and bicarbonate) in patients with advancing CKD should be managed closely to avoid adverse effects on the cardiovascular and skeletal systems.     

慢性肾脏病患者血清β2微球蛋白与颈动脉粥样硬化的关系

目的 研究慢性肾脏病（CKD）患者血清β2微球蛋白（β2MG）水平的变化及与颈动脉粥样硬化的关系.方法 对168例CKD患者（非透析治疗120例,血液透析48例）的临床及实验室资料作回顾性研究,采用电化学发光免疫法（ECLIA）检测血清β2MG水平,应用颈动脉超声检查颈动脉病变的程度,分析β2MG水平与颈动脉粥样硬化的关系.结果 CKD患者无论透析与否,β2MG水平均较健康对照组显著升高[（18.6±2.91）比（2.18±0.49） μg/mL,P＜0.01],在非透析CKD患者中,随着肾小球滤过率（GFR）的逐渐下降,血β2MG水平也逐渐升高,各组间比较差异有统计学意义（P＜0.05或P＜0.01）,且CKD5D期β2MG水平较CKD5期更高（P＜0.05）;CKD患者颈动脉内膜中层厚度（IMT）[（0.71±0.18）比（0.67±0.21）mm,P＜0.01]及斑块形成（28.7％比12.0％,P＜0.01）、颈动脉硬化的患病率（32.9％比12.0％,P＜0.01）较健康对照组均显著升高,CKD5D期上述指标较CKD5期均更高（均P＜0.05）;直线相关分析显示,血β2MG水平与hsCRP、TG、Lp （a）、血磷、iPTH、24h尿蛋白定量、透析龄及IMT、斑块形成、颈动脉硬化的患病率呈正相关（P ＜0.05或P＜0.01）,而与GFR、血白蛋白（SA1b）、血红蛋白（Hb）、血钙呈负相关（P ＜0.05或P＜0.01）;多因素逐步回归分析显示,β2MG、hsCRP和年龄是CKD患者颈动脉病变的独立危险因素. 结论 各期CKD患者β2MG水平均显著升高,且与hsCRP及颈动脉病变相关,血β2MG升高可能是CKD患者并发动脉粥样硬化的危险因素之一.     

慢性肾脏病不同分期患者认知功能水平的研究

目的探讨慢性肾脏病（chroniCkidneYdisease,CKD）不同分期患者认知功能水平的变化。方法入选2010年5月至2012年4月在北京博爱医院肾内科就诊的CKD患者,根据基于肌酐的肾小球滤过率（GFR）评估公式估测的GFR（eGFR）水平将患者分为CKD1—2期组、CKD3—4期组、CKD5期组,其中CKD5期组又根据透析与否分为CKD5期非透析组、CKD5期透析组。应用中国修订韦氏成人智力量表（WAIS—RC）进行认知功能水平的评估。采用单因素方差分析法对CKD不同分期患者的认知功能水平进行比较。结果共入选103例CKD患者,包括CKD1—2期31例,平均年龄（54．77±12．70）岁;CKD3—4期25例,平均年龄（62．24±14．36）岁;CKD5期非透析组10例,平均年龄（60．03±12．10）岁;CKD5期透析组37例,平均年龄（65．00±14．41）岁。CKDl—2期组、CKD3—4期组、CKD5期非透析组、CKD5期透析组患者总智商评分分别为102．00±18．09、90．80±18．87、93．2±15．66、94．14±22．48（F值=1．69,P=0．17）;言语智商评分分别为103．10±15．31、92．68±20．68、90．61±19．54、98．73±17．86（F值=2．13,P=0．10）;操作量表评分分别为98．74±2．04、87．88±20．68、94．90±15．72、95．00±17．53（F值=1．25,P=0．30）。随着eGFR的下降,CKD不同分期患者的认知功能水平呈现部分下降的趋势,4组之间在总智商、语言智商、操作智商方面尚未达到统计学差异（P〉0．05）。结论CKD不同分期的患者,随着eGFR的下降,患者的认知功能有一定程度的下降趋势。     

慢性肾脏疾病患者各期骨形态蛋白-2水平变化及其影响因素

目的探讨慢性肾脏疾病(chronic kidney disease,CKD)1-5期患者血清骨形态蛋白-2(Bone morphogenetic protein2,BMP-2)水平变化及其可能的影响因素。方法收集CKD各期的154例血液样本。测定血清BMP-2水平和常规生化测定肾功能、白蛋白、C-反应蛋白(CRP)及钙磷代谢等。并进行相关及多元回归分析。结果 CKD1～5期各有26、22、26、20、28例,血液透析32例,对照28例。与正常对照比较,CKD4,CKD5期及血液透析患者血清BMP-2水平明显升高;血清BMP-2水平在CKD患者下列情况下显著升高:血磷大于1.4mmol/L或钙磷沉积大于55mg2/dl2;血清白蛋白低于35g/L;C-反应蛋白大于3000μg/L。相关分析结果提示,BMP-2与血磷水平,钙磷乘积,C-反应蛋白,血尿素氮,血肌酐呈显著正相关;与血清白蛋白和肾小球滤过率呈显著负相关。多元回归分析示:血磷及CRP显著影响BMP-2的独立因素。结论 BMP-2在CKD中晚期和血液透析患者血清中明显升高;残存肾功能、钙磷代谢、炎症和白蛋白可能与CKD患者血清BMP-2水平有关;血磷和炎症是影响BMP-2的主要因素。     

早期干预钙磷代谢对慢性肾脏病血管钙化的影响

目的观察慢性肾脏病(chronic kidney disease,CKD)3期开始纠正钙磷代谢紊乱对CKD患者桡动脉血管钙化的防治作用。方法入选南方医科大学附属南海医院CKD3、4和5期非透析患者106例,随机分为干预组及对照组,干预组进行钙磷代谢达标治疗。待进展到终末期肾病并行维持性血液透析治疗前作动静脉内瘘术并取部分桡动脉观察血管钙化程度及骨桥蛋白(osteopontin,OPN)、á平滑肌肌动蛋白(alpha smooth muscle actin,á-SMA)的表达。结果 49例进入终末期肾病患者茜素红染色提示干预组血管钙化病例减少且程度明显减轻,免疫组化提示钙化病例较未钙化病例OPN表达增多、á-SMA表达减少,干预组较对照组OPN表达相对减少、á-SMA表达相对增多。结论从CKD3和4期开始纠正钙磷代谢紊乱能有效减轻尿毒症患者桡动脉血管钙化。OPN、á-SMA的表达变化先于明确钙化表现,OPN表达量与钙化正相关,á-SMA表达量与钙化负相关。     

Induction and function of vascular adhesion protein-1 at sites of inflammation

Emigration of leukocytes from the blood into the tissues is critical in controlling lymphocyte patrolling in different lymphatic organs and in leukocyte accumulation at sites of inflammation. During the first stage of the extravasation process, leukocytes bind to the endothelial lining of vessels. At the molecular level, several adhesion molecules on leukocytes and endothelial cells function as receptor-ligand pairs in mediating this dynamic interaction. Recently, we have identified a novel human endothelial cell molecule, vascular adhesion protein 1 (VAP- 1), that mediates lymphocyte binding (Salmi, M., and S. Jalkanen. 1992. Science [Wash. DC] 257:1407). VAP-1 was initially characterized by mAb 1B2 which inhibits lymphocyte adhesion to high endothelial venules (HEV) and to purified VAP-1 protein. Here we report the location and function of VAP-1 in normal and inflamed tissues in humans. VAP-1 is abundant in HEV of lymphatic organs belonging to the peripheral lymph node system, but considerably less is expressed in vessels of mucosa- associated lymphatic tissues. A subset of venules in most normal nonlymphatic tissues like skin, brain, kidney, liver, and heart is also VAP-1 positive. In addition to vessels, VAP-1 is distributed on a few other cell types, most notably in dendritic-like cells of germinal centers. At sites of inflammation, such as in inflammatory bowel diseases and chronic dermatoses, expression of VAP-1 is clearly increased. The induced VAP-1 is functional, since mAb 1B2 inhibits lymphocyte binding to inflamed lamina propria venules by approximately 60%. Thus VAP-1 is an endothelial adhesion molecule that under normal conditions is expressed mainly in HEV of lymphatic tissues. However, expression of functional VAP-1 in vivo is upregulated during an inflammatory reaction at other sites as well. Inducibility of VAP-1 suggests that it may play a significant role, not only in recirculation of lymphocytes, but also in controlling entry of leukocytes into sites of inflammation.