Associations of plasma pentraxin 3 and monocyte chemoattractant protein-1 concentrations with cardiovascular disease in patients with chronic kidney disease

Both pentraxin 3 (PTX3) and monocyte chemoattractant protein-1 (MCP-1) are mediators of inflammation. They also appear to play critical roles in vascular endothelial dysfunction but their associations with cardiorenal syndrome remain largely unknown. The objective of this study was to examine their associations with cardiorenal syndrome. Circulating levels of PTX3, MCP-1, and some other biomarkers were evaluated in 134 patients with chronic kidney disease (CKD) and/or cardiovascular disease (CVD) and 55 age- and gender-matched subjects without CKD or CVD. Levels of PTX3, high-sensitivity C-reactive protein (hsCRP), and tumor necrosis factor α (TNFα) were significantly higher in CKD patients with CVD than in those without CVD. In advanced CKD patients (estimated glomerular filtration rate < 30 mL/min/1.73 m2), the values of area under the curve of PTX3, TNFα, and hsCRP for the detection of the association of CVD were 0.664, 0.507, and 0.318, respectively. In contrast, serum levels of MCP-1 were significantly higher in CKD patients than in control subjects independently of association with CVD. PTX3, hsCRP, and TNFα, but not MCP-1 could predict the presence of CVD as a complication associated with CKD. Additionally, PTX3 might be a more sensitive marker for the association of CVD than hsCRP and TNFα in patients with advanced CKD.     

血浆五聚素3水平与血液透析患者心血管疾病的相关性

目的 探讨血液透析患者血浆五聚素3（PTX3）水平与心血管疾病（CVD）的关系。 方法 选取稳定的维持性血液透析(MHD)3个月以上的患者为对象,以体检健康人为对照组。用ELISA法测定血浆PTX3。用Spearman相关和线性回归分析PTX3与其他指标的相关性。用二分类Logistic回归方法分析PTX3与CVD的关系。用受试者工作特征（ROC）曲线分析PTX3及高敏C反应蛋白（hsCRP）与CVD的相关性。 结果 共98例MHD患者入选,其血浆PTX3水平显著高于对照组[1.87（1.34~2.50） μg/L比1.11（0.86~1.51） μg/L,P < 0.01];单次血液透析后血浆PTX3水平显著高于透析前[2.18（1.80~3.14） μg/L比1.87（1.34~2.50） μg/L,P < 0.01]。并发CVD患者血浆PTX3水平显著高于非CVD患者[2.18（1.48~2.74） μg/L比1.76（1.25~2.26） μg/L,P < 0.05]。二分类Logistic回归分析显示PTX3水平升高对并发CVD的优势比为3.15 [95%CI（1.17~8.50）,P < 0.05]。针对CVD的ROC曲线分析显示,当hsCRP>3 mg/L时,PTX3的曲线下面积为0.655±0.083（P < 0.05）;而hsCRP的曲线下面积为0.562±0.083（P ＞ 0.05）。Spearman相关分析显示,血浆PTX3与体质量指数（ρ = -0.248,P < 0.05）、前白蛋白（ρ = -0.218,P < 0.05）、总胆固醇（ρ = -0.265,P < 0.01）、三酰甘油（ρ = -0.246, P < 0.05）、低密度脂蛋白胆固醇（ρ = -0.254,P < 0.05）、血红蛋白（ρ = -0.212,P < 0.05）呈负相关;与每周红细胞生成素剂量（ρ = 0.184,P < 0.01）、肌钙蛋白T（ρ = 0.287,P < 0.01）、 颈动脉内膜中层厚度（ρ = 0.294,P < 0.05）呈正相关。 结论 MHD患者血浆PTX3水平显著升高。血液透析过程可诱发PTX3升高。血浆PTX3与MHD患者CVD独立相关,可作为血液透析患者CVD危险因素标志物。     

Plasma Pentraxin 3 is Associated with Cardiovascular Disease in Hemodialysis Patients

Abstract

This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.     

血浆五聚素3与慢性肾脏病非透析患者心血管疾病的相关性

目的探讨血浆五聚素3（pentraxin3,PTX3）水平与慢性肾脏病（CKD）非透析患者心血管疾病（cardio vascular disease,CVD）的关系。方法选择CKD3～5期非透析患者90例分为CKD非CVD组（A组,58例）和CKD合并CVD组（B组,32例）;另选健康正常者15名为健康对照组。收集CKD患者临床资料、相关生化指标。用放免法测定PTX3、超敏C反应蛋白（hs—CRP）及彩超测定颈动脉内膜中层厚度（IMT）。采用ROC曲线分析PTX3、hs—CRP与CVD的相关性。相关性分析采用Pearson相关分析法。结果①A、B组PTX3、hS-cRP等炎症介质均明显高于健康对照组（P〈0．05）。②B组PTX3、hs—CRP均明显高于A组（P〈0．05）。③针对CⅧ的ROC曲线分析显示,PTX3与CKD患者的CVD关系更为密切,PTX3曲线下面积为0．860（P〈0．01）,当检测的截点为6．73μg／L时,其敏感性为75％,特异性为89．7N;hs—CRP曲线下面积为0．622（P〈0．05）,当检测的截点为11．23mg／L时,其敏感性为62．5％,特异性为55．2％。④A、B组IMT均明显高于健康对照组（P〈0．05）。B组比A组IMT呈逐渐增厚趋势,但无统计学意义（P〉0．05）。IMT与PTX3呈正相关（r=0．372,P〈0．05）。结论CKD患者体内都存在炎症状态,PTX3、hs—CRP均高于健康人。与CRP相比,PTX3与CKD患者的CVD关系更为密切。它可作为CKD患者CVD的危险因素观察指标之一。     

慢性肾脏病患者血清1,25（OH）2D水平与蛋白尿及尿炎症细胞因子相关性研究

目的：探讨慢性肾脏病（CKD）1～4期患者血清1,25（OH）2D水平与蛋白尿、尿炎症细胞因子的关系。方法：对我科115例CKD1～4期患者及20例健康对照者进行血清1,25（OH）2D、血CRP,尿TGF-β1、MCP-1、TNF、IL-6,24h尿蛋白定量检测;分析血清1,25（OH）2D水平与以上指标相关性。结果：（1）CKD组患者血清1,25（OH）2D水平低于对照组（P〈0.05）;血CRP,尿MCP-1、TGF-β1、IL-6、TNF水平,24h尿蛋白定量高于对照组（P〈0.05）。（2）与GFR≥60ml·min^-1·1.73m^-2患者比较：GFR〈44ml·min^-1·1.73m^-2患者CRP,尿MCP-1、TGF-β1、IL-6、TNF水平、24h尿蛋白定量升高（P〈0.05）;血清1,25（OH）2D水平降低（P〈0.05）;而GFR45～59ml·min^-1·1.73m^-2患者与GFR≥60ml·min^-1·1.73m^-2患者比较,两组间差异无统计学意义（P〉0.05）;（3）单因素相关分析显示CKD患者血清1,25（OH）2D与年龄（r=-0.442）、收缩压（r=-0.464）、舒张压（r=-0.399）、GFR（r=0.902）、Scr（r=-0.430）、PTH（r=-0.341）、UA（r=0.237）、24h尿蛋白定量（r=-0.372）及尿TGF-β1（r=-0.894）、MCP-1（r=-0867）、TNF（r=-0.899）、IL-6（r=-0.934）水平相关（P〈0.05）。多元回归分析显示血清1,25（OH）2D与GFR呈正相关;与24h尿蛋白定量,尿MCP-1、IL-6,血Scr、PTH呈负相关。结论：CKD1～4期患者存在1,25（OH）2D水平降低,并与蛋白尿及尿炎症细胞因子水平密切相关。     

血浆五聚素3水平在血液透析患者外周动脉疾病中的意义

目的 通过检测血液透析（血透）患者血浆五聚素3（PTX3）水平和踝臂指数（ABI）,探讨PTX3在血透患者外周动脉疾病（PAD）发生发展中的可能作用。 方法 选取接受规律性血透3个月以上患者。根据ABI将血透患者分为PAD组（ABI＜0.9）和非PAD组（ABI≥0.9）。收集血透患者临床资料、相关生化指标和炎性反应指标。选取体检健康人为对照组。用ELISA方法测定各组血浆PTX3水平。用Logistic回归方法分析PAD与PTX3及其它因素间的关系。 结果 本中心116例血透患者入选。PAD的发生率为18.1%（21/116）。血透患者血浆PTX3水平显著高于对照组[（2.90±1.03） μg/L比（1.70±0.85） μg/L,P ＜ 0.01];PAD组血浆PTX3水平显著高于非PAD组[（5.55±2.63） μg/L比（2.32±1.29） μg/L,P ＜ 0.01]。单变量分析显示ABI 与PTX3水平（r = -0.548,P ＜ 0.01）、超敏C反应蛋白（hsCRP）水平（r = -0.495,P ＜ 0.01）均呈负相关。PAD的ROC曲线分析显示,PTX3曲线下面积为0.901（P ＜ 0.01）,当以4.06 μg/L为检测截点时,其敏感性和特异性分别为81.0%和91.5%;hsCRP曲线下面积为0.640（P ＜ 0.05）,当检测的截点为3.33 mg/L时,其敏感性和特异性分别为57.1%和56.8%。Logistic回归分析显示,PTX3血浆浓度上升对PAD的优势比（OR）值为9.755 （95%CI：2.359～19.354,P = 0.001）。 结论 本中心规律性血透患者PAD发生率为18.1％。血透患者血浆PTX3水平显著高于健康对照组。PAD与血浆PTX3水平升高相关。PTX3作为诊断PAD的参考指标,其特异性和敏感性均优于hsCRP。     

慢性肾脏病住院患者白蛋白尿与心血管疾病相关性研究

目的：研究慢性肾脏病（CKD）住院患者白蛋白尿与心血管疾病（CVD）的相关性,探讨白蛋白尿对非糖尿病CKD患者CVD的预测价值。方法：回顾性分析1245例非糖尿病CKD患者的一般情况、生化指标、心电图、胸部X线、心超及CVD的危险因素。结果：（1）1245例患者中CKD1、2、3、4、5期分别为304例（24.4%）、281例（22.6%）、372例（29.9%）、157例（12.6%）、131例（10.5%）;CKD1～5各期有蛋白尿者分别为208例（68.8%）、194例（69%）、269例（72.3%）、117例（74.5%）、106例（80.9%）。（2）与CKD1期患者相比,CKD2～5期患者年龄、SBP、DBP、Scr、UA明显升高,eGFR、Hb、Alb明显降低（P〈0.05）;CKD3期患者TG、LDL升高,HDL降低（P〈0.05）;CKD4、5期患者TC、LDL、HDL降低;TG升高（P〈0.05）。（3）与CKD同期非白蛋白尿组相比,白蛋白尿组CKD1～5期患者Scr、UA明显升高,Alb明显降低（P〈0.05）;CKD2～5期患者SBP、DBP明显升高,eGFR、Hb明显降低（P〈0.05）;CKD4、5期患者TC、HDL降低,TG、LDL升高（P〈0.05）。（4）CKD患者CVD发病率从CKD1～CKD5期逐步升高（P〈0.05）,白蛋白尿患者CVD发病率以及胸部X片、心电图、心超异常阳性率升高更加明显（P〈0.05）。（5）Logistic回归分析显示CVD与年龄、SBP、UA、TG、白蛋白尿呈现正相关,与GFR、Hb呈现负相关（P〈0.05）。结论：非糖尿病CKD患者CVD发病率随CKD进展而增高,与白蛋白尿密切相关,白蛋白尿是CVD患者心血管疾病危险标志。     

The association of serum inflammatory biomarkers with chronic kidney disease in hypertensive patients

A positive association between inflammation and chronic kidney disease (CKD) has been reported but the impact of hypertension on this relation remains unclear. The aim of this study is to investigate the association of various inflammation markers with risk of CKD in hypertensive patients. 387 hypertensive patients (mean age 55.5 years) were recruited. Serum matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1(TIMP-1), high-sensitivity C-reactive protein (hsCRP) and osteopontin (OPN) were measured by ELISA. CKD was diagnosed either as evidence of kidney damage, including microalbuminuria, or by low glomerular filtration rate (GFR) (<60?mL/min/1.73?m²), which was estimated using the Modification of Diet in Renal Disease (MDRD) abbreviated equation. Compared with the reference groups (eGFR?≥?60?mL/min/1.73?m²), the serum levels of TIMP-1, OPN, hsCRP were significantly higher, and the MMP-9/TIMP-1 ratio was lower in the risk group (eGFR?2). Multiple logistic regression analysis showed that TIMP-1, MMP-9/TIMP-1 ratio, OPN and hsCRP were associated with low GFR separately after adjustment, whereas MMP-9/TIMP-1 ratio, OPN and hsCRP were associated with microalbuminuria. The significant association of MMP-9/TIMP-1 ratio and OPN with low GFR and microalbuminuria persisted after additional adjustment for other studied inflammatory biomarkers. Our data suggest that inflammation is strongly and independently associated with renal damage in hypertensive patients. MMP-9/TIMP-1 ratio and OPN may serve as novel risk factors and therapeutic targets for the treatment of CKD in hypertensive patients.     

MCP-1 and soluble TWEAK levels are independently associated with coronary artery disease severity in patients with chronic kidney disease

Abstract

Purpose: Patients diagnosed with chronic kidney disease (CKD) have a greater rate of cardiovascular mortality when compared with the general population. The soluble form of TNF-like weak inducer of apoptosis (TWEAK) and monocyte chemoattractan protein 1 (MCP-1) play important roles in cellular proliferation, migration and apoptosis. The current study aimed to analyze whether soluble TWEAK (sTWEAK) and MCP-1 levels are associated with the severity of coronary arterial disease (CAD) in CKD patients. Methods: Ninety-seven patients diagnosed with CKD stages 2–3 according to their estimated glomerular filtration rate and the presence of kidney injury were included in the study. Plasma sTWEAK and MCP-1 concentrations were determined using commercially available ELISA kits. Coronary angiographies were performed through femoral artery access using the Judkins technique. Results: Correlation analysis of sTWEAK and Gensini scores showed significant association (p?<?0.01, r²?=?0.287). Also significant correlation has been found in MCP-1 levels and Gensini scores (p?<?0.01, r²?=?0.414). When patients were divided into two groups with a limit of 17 according to their Gensini score, sTWEAK levels indicated a statistically significant difference (p?<?0.01). Conclusions: Our findings support a relationship between sTWEAK and MCP-1 levels and CAD in CKD stages 2–3 patients.     

Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases

Proteinuria (albuminuria) reflects dysfunction of the glomerular permeability barrier in which inflammatory cytokines play a key role. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses potent anti-inflammatory and immunomudulatory effects. This study evaluated the effectiveness of PTX to reduce proteinuria and inflammatory mediators in patients with proteinuric primary glomerular diseases. Seventeen patients with primary glomerular diseases, a persistent spot proteinuria exceeding 1.5 g/g creatinine (Cr) and a glomerular filtration rate between 24 and 115 ml/min/1.73 m(2) were treated with PTX 400 mg twice daily for 6 months. Before and after the treatment, serum Cr, plasma renin activity and aldosterone concentrations, plasma and urinary tumor necrosis factor (TNF)-alpha, interleukin-1beta and monocyte chemoattractant protein (MCP)-1, as well as urinary protein and Cr were measured. PTX significantly reduced urinary protein excretion, along with an increase of serum albumin. A significant correlation existed between the basal urinary protein/Cr and the basal urinary MCP-1/Cr ratios. PTX lowered the urinary MCP-1/Cr ratio, and the percent reduction of urinary protein/Cr ratio correlated directly with the precent decrease of urinary MCP-1/Cr ratio after PTX treatment. There was no significant change in blood pressure, renal function, biochemical parameters, plasma renin activity and aldosterone concentrations, or plasma TNF-alpha and MCP-1 levels during the study. In conclusion, administration of PTX 800 mg per day is safe and effective for reducing proteinuria in patients with proteinuric primary glomerular diseases. This beneficial effect occurs in close association with a reduction of urinary MCP-1 excretion.     

Plasma pentraxin 3 is associated with cardiovascular disease in hemodialysis patients

This cross-sectional study evaluates the associations of Pentraxin 3 (PTX3) and cardiovascular disease (CVD) in hemodialysis (HD) patients. Plasma was obtained from 98 maintenance HD patients before and after a session of HD and 50 age-matched healthy subjects. We measured plasma PTX3 levels by enzyme-linked immunosorbent assay. Our results showed that plasma PTX3 levels were significantly higher in HD patients compared with controls (1.87 vs. 1.11 ng/mL, p < 0.001), and increased acutely after a single HD session (post-HD 2.18 ng/mL vs. pre-HD 1.87 ng/mL, p < 0.001). Patients with CVD had higher plasma PTX3 levels than those without CVD (2.18 vs. 1.76 ng/mL, p < 0.05). Plasma PTX3 levels correlated positively with cardiac troponin T (ρ = 0.287, p = 0.007) and carotid artery intima-media thickness (ρ = 0.294, p = 0.043). High plasma PTX3 (>1.87 ng/mL) level was positively and independently associated with CVD (OR = 3.15, p = 0.024). Receiver operator characteristics analysis showed the correlation between PTX3 and CVD more closely than high sensitivity C-reactive protein (hs-CRP) in patients whose hs-CRP were higher than 3 mg/L. The area under the curve for PTX3 and hs-CRP was 0.655 (p = 0.047) and 0.562 (p = 0.458), respectively. Moreover, plasma PTX3 levels correlated negatively with body mass index, hemoglobin, pre-albumin, total cholesterol, triglyceride, and low-density lipoprotein. These data support the main conclusions: PTX3 levels are markedly elevated in HD patients; HD procedure itself induces PTX3 elevation; plasma PTX3 is associated with CVD in maintenance HD patients.     

Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease.

BACKGROUND: Pentraxins are mediators of inflammation as well as markers of the acute-phase reaction. While elevation of C-reactive protein (CRP) in patients with renal failure and its association with cardiovascular disease is well described, there are no data on pentraxin 3 (PTX3) in this population. METHODS: Plasma was obtained from 44 chronic haemodialysis (HD) patients, 35 peritoneal dialysis (PD) patients, 39 patients with chronic renal failure (CRF) not on dialysis therapy and 14 age-matched normal subjects. PTX3 production in whole blood was also investigated in samples taken before and during HD. RESULTS: PTX3 plasma levels were significantly higher in HD patients (5.8 +/- 0.6 ng/ml) compared with the other three groups. There were no significant differences between PD patients (1.5 +/- 0.4 ng/ml), CRF patients (1.5 +/- 0.4 ng/ml) and normal subjects (0.76 +/- 0.2 ng/ml). In dialysis patients, PTX3 levels correlated significantly with time on renal replacement therapy (RRT) and with weekly erythropoietin dose. PTX3 levels were significantly higher in patients with coronary artery disease and peripheral artery disease compared with those without. During a single HD session, PTX3 production was higher in whole blood samples taken after 3 h HD compared with samples taken before HD. CONCLUSIONS: PTX3 levels are markedly elevated in HD patients. The increase in PTX3 production in whole blood after HD indicates that the HD procedure itself contributes to elevated PTX3 levels in HD patients. The association between PTX3 and cardiovascular morbidity suggests a possible connection of PTX3 with atherosclerosis and cardiovascular disease in HD patients.     

Intraindividual Interleukin-6 Variations on the Cardiovascular Prognosis of Patients with Chronic Renal Disease

In chronic kidney disease (CKD) patients on dialysis, plasma interleukin (IL)-6 levels predict mortality better than other markers. Impact of intraindividual changes of inflammatory markers on cardiovascular (CV) events in CKD patients is unknown. The aim of this study is to demonstrate the relation between CV outcomes and variations of C-reactive protein (CRP), IL-6, IL-1β, and tumor necrosis factor (TNF)-α in CKD. Ninety patients (mean age: 68.5 ± 12.8 years) at different stages (1–4) of CKD were evaluated. Serum CRP, IL-6, IL-1β, and TNF-α were measured basally and after taking statins or angiotensin II receptor blockers. Three patterns were defined for each marker (baseline, mean of two measurements, and variation of the marker: increase or decrease after 6 months). During follow-up (mean time: 72.7 ± 19.8 months), 14 patients died, 11 were included on dialysis program, and 29 suffered a CV event. Patients with persistently elevated IL-6 values had higher risk to develop CV events [OR = 1.21 (1.11–1.32), p = 0.001]. Mean of two measurements of IL-6 was a better predictor for events than a single measurement of IL-6, CRP, TNF-α, and IL-1β. A mean of two determinations of plasma IL-6 greater than 6 pg/mL and previous peripheral vascular disease was related to an increased risk for CV events [2.34 (1.05–5.22), p = 0.037 and 2.95 (1.27–6.93), p = 0.011, respectively] in an adjusted Cox regression model. IL-6 is a better inflammatory marker than CRP, TNF-α, and IL1β at predicting CV events in CKD nondialysis patients. Mean of two measurements is better than simple determinations at predicting CV outcome.     

Possible new role of monocyte chemoattractant protein-1 in hemodialysis patients with cardiovascular disease

AIMS: Reactive oxygen species have been implicated in increased vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP-1) levels in vascular cells, which may promote atherosclerosis progression. METHODS: We studied the association between pre-dialysis plasma levels of VEGF and MCP-1 in 45 hemodialysis (HD) patients with and without cardiovascular disease (CVD) in conditions of increased oxidative stress (SOX). RESULTS: Compared to the controls, HD patients, especially those with CVD, showed a significant increase in plasma concentrations of Cu/Zn superoxide dismutase (Cu/Zn SOD), C-reactive protein (CRP), MCP-1 and VEGF. The levels of CRP, MCP-1 and VEGF were more increased in patients with CVD than in patients without CVD (all p < 0.01). VEGF strongly and positively correlated with MCP-1 only in HD patients with CVD. Additionally, both VEGF and MCP-1 were associated with Cu/Zn SOD in the whole HD group. CONCLUSION: For the first time our data indicate a correlation between VEGF and MCP-1 levels in HD patients with CVD in conditions of increased SOX. This interaction may reflect the new role of MCP-1 as an arteriogenic factor in HD patients with CVD.     

慢性肾脏病患者血清游离脂肪酸与心脏结构和功能的关系

目的：研究慢性肾脏病（CKD）患者不同时期血清游离脂肪酸（FFA）和高敏C反应蛋白（hs-CRP）水平的变化及与心脏结构和功能的关系。方法：对188例CKD患者（非透析治疗130例,血液透析58例）的临床及实验室资料作回顾性研究,应用酶比色法检测血清FFA、免疫比浊法检测hs-CRP,并应用心脏超声心动图测定患者的心脏结构和功能,分析FFA水平的变化与心脏结构和功能的关系。结果：CKD患者无论透析与否,FFA水平较健康对照组显著升高[（492.63±143.59）vs（302.65±142.18）μmol/L,P〈0.01],hs-CRP水平较健康对照组显著升高[（8.11±3.85）vs（4.63±1.34）mg/L,P〈0.01],在非透析CKD患者中,随着肾功能的逐渐减退,血FFA和hs-CRP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HD组FFA和hs-CRP水平较非透析CKD各组更高（P〈0.05）;直线相关分析显示,血FFA水平与hs-CRP、左心室心肌重量指数（LVMI）、心脏功能综合指数（Tei指数）、TG呈正相关（P〈0.05,P〈0.01）,与LVEF、GFR呈负相关（P〈0.05）;多因素逐步回归分析显示,FFA、hs-CRP和年龄是CKD患者心脏结构和功能异常的危险因素。结论：大约50%CKD患者FFA水平明显升高,且与hs-CRP及心脏结构和功能异常相关,提示高游离脂肪酸血症是CKD患者并发心血管疾病的危险因素之一。     

慢性肾脏病非透析患者脑钠素与动脉粥样硬化及心功能的关系

目的 研究脑钠素（BNP）与慢性肾脏病（CKD）非透析患者动脉粥样硬化及心功能不全的关系。 方法 采用双抗夹心免疫荧光法检测203例CKD非透析患者与16例高血压患者对照组全血BNP水平，分析其与颈动脉超声结果、心脏彩超结果及既往心血管疾病史的关系。 结果 CKD非透析患者BNP水平与对照组相比显著升高[M（范围）：54.40(15.10～ 173.00) ng/L比9.35(7.35～15.00) ng/L，P < 0.01]。Spearman相关分析显示CKD患者BNP与颈动脉内膜中层厚度（IMT）、左室心肌重量指数（LVMI）等呈正相关。存在颈动脉斑块、左室肥厚或既往发生过心血管事件的患者血BNP水平显著增高。多元回归分析显示LVMI、既往心血管事件均是影响BNP水平的独立因素。 结论 CKD非透析患者BNP水平和动脉粥样硬化性疾病、左室肥厚及心功能不全相关，提示BNP水平可作为一项评价CKD非透析患者心功能及动脉粥样硬化的敏感生物学指标。     

Chronic kidney disease stages 3–5 and cardiovascular disease in the veterans affairs population

Aim  Cardiovascular complications are common in patients with chronic kidney disease in the general population. The study aims to investigate the prevalence and prognosis of CKD stages 3–5 in the veterans affairs (VA) population, which is sicker with more co-morbid conditions. Methods  In this case-controlled study of 6,432 men the associations of risk factors with CKD and its risk of mortality were estimated using, primarily, logistic regression analysis. Results  The 1,045 (16.2%) patients with CKD stages 3–5 were older (72 ± 10 vs. 59 ± 13 years, P < 0.0001) with more hypertension (53.6 vs. 39.6%, P < 0.0001), diabetes (24.9 vs. 19.8%, P < 0.0002), and CVD (35.3 vs. 17.8%, P < 0.0001) at baseline. Age ≥65 years (odds ratio [95% CI]) (4.95 [4.22–5.82]), hypertension (1.56 [1.34–1.79]), diabetes mellitus (1.21 [1.03–1.43]), CVD (1.71 [1.47–2.00]), and White not Hispanic (1.57 [1.32–1.85]) were independently associated with CKD. The prevalence of CVD at baseline increased with decreasing renal function. Old age (1.98 [1.66–2.35]), CKD (1.94 [1.61–2.33], CVD (1.46 [1.23–1.74]) and tobacco use (1.91 [1.05–3.47]) were independently associated with the 750 (11.7%) deaths. Conclusion  Among veterans, traditional cardiovascular risk factors, CVD, and CKD are highly prevalent. CKD is associated with increased risk of baseline CVD and follow-up mortality.     

Association of Preventive Health Care with Atherosclerotic Heart Disease and Mortality in CKD

Chronic kidney disease (CKD, stages 1 to 4) affects approximately 13.1% of United States adults and leads to ESRD, cardiovascular disease, and premature death. Here, we assessed adherence to a subset of Kidney Disease Outcomes Quality Initiative preventive health care guidelines and identified associations between adherence and incident atherosclerotic heart disease (ASHD). Using the Medicare 5% data set, 1999 to 2005 (about 1.2 million patients per year), we created 3-yr rolling cohorts. We classified CKD and diabetes during year 1, assessed preventive care during year 2, and evaluated ASHD outcomes during year 3. We defined preventive care by the receipt of laboratory measurements (serum creatinine, lipids, calcium and phosphorus, parathyroid hormone, and, for patients with diabetes, hemoglobin A1c), influenza vaccination, and by at least one outpatient visit to a nephrologist. Among patients with CKD, 80% received ≥2 serum creatinine tests during the year, and only 11% received parathyroid hormone testing. Cumulative incidence of the combined ASHD outcome was 25% and 11% for patients with and without prevalent cardiovascular disease, respectively. Except for serum creatinine testing, preventive care associated with lower ASHD rates in the subsequent year, ranging from 10% lower for those who received influenza vaccinations and ≥2 A1c tests, to 43% lower for calcium-phosphorus assessment. Receiving ≥2 serum creatinine tests associated with a 13% higher rate of ASHD. A higher number of preventive measures associated with lower rates of ASHD. In summary, these data support an association between preventive measures and reduced cardiovascular morbidity and mortality.Chronic kidney disease (CKD, stages 1 to 4) is estimated to affect 13.1% (12.0% to 14.1%) of the adult noninstitutionalized civilian United States population, or 26.3 million adults according to the 2000 census.¹ The prevalence rate increased approximately 30% between the early 1990s and the early 2000s.¹ In 2002, the Kidney Disease Outcomes Quality Initiative (KDQOI) Clinical Practice Guidelines committee, organized by the National Kidney Foundation (NKF), noted that the three primary adverse consequences of CKD are kidney failure, cardiovascular disease (CVD), and premature death.² The committee further noted that CVD is common, treatable, and potentially preventable in CKD patients, and that CKD appears to be a risk factor for CVD.² In 1998, the NKF Task Force on Cardiovascular Disease in Chronic Renal Disease recommended that CKD patients be considered in the highest risk group for CVD events.³Two recent studies demonstrate increasing incidence of cardiovascular events⁴ and increasing prevalence of cardiovascular risk factors⁵ with decreasing GFR. An analysis of secondary cardiovascular events following myocardial infarction demonstrates increasing probability of subsequent cardiovascular events with decreasing GFR.⁶ United States Renal Data System (USRDS) analyses demonstrate hospitalization rates for congestive heart failure (CHF), ischemic heart disease, and arrhythmias two to seven times higher for Medicare patients with CKD than for those without CKD,⁷ and that CKD patients with no prior evidence of CVD were 60% more likely to develop CVD during the subsequent year than non-CKD patients.^8,9The USRDS notes that CKD patients are three to five times more likely to die than to reach ESRD¹⁰ and that nearly half of CKD patient deaths occur out of the hospital, presumably sudden cardiac death.⁸ A recent meta-analysis found that the relative risk of all-cause mortality comparing CKD to non-CKD patients ranged from 0.94 to 5.00 in all cohorts analyzed and was significantly more than 1.0 in 93% of the cohorts; it also found an increasing risk of all-cause mortality with decreasing GFR.¹¹The Healthy People 2010 initiative of the Centers for Disease Control and Prevention includes objectives intended to preserve renal function and slow CKD progression through early detection and intervention.¹² The NKF has published numerous clinical practice guidelines addressing ESRD and CKD,^2,13–15 with the goals of identifying CKD early, slowing its progression, and reducing associated morbidity and mortality.Our objectives were to assess adherence to KDOQI recommendations for CKD care and subsequent associations between preventive care and incident atherosclerotic heart disease (ASHD) in the general Medicare population with evidence of CKD. Preventive care measures assessed include monitoring of serum creatinine, lipids, calcium-phosphorus, parathyroid hormone (PTH), glycated hemoglobin (A1c) in diabetic patients; influenza vaccinations; and outpatient nephrologist office visits. Subsequent ASHD outcomes studied include acute ischemic heart disease events, angina pectoris, cardiac arrest, coronary revascularization procedures, and all-cause death. Data were from the 5% Medicare 1999 to 2005 random sample limited data set standard analytic files.     

Malnutrition and inflammation are associated with impaired pulmonary function in patients with chronic kidney disease.

BACKGROUND: Inflammation and malnutrition are common findings in patients with chronic kidney disease (CKD). We hypothesized that in inflamed and malnourished patients, respiratory and peripheral muscle dysfunction may have significant consequences on pulmonary function. The aim of this study was to investigate possible associations between pulmonary function and inflammation and malnutrition in patients with CKD. METHODS: We studied 109 patients (63% males; 53+/-12 years) at the initiation of dialysis treatment (GFR 7.5+/-2.5 ml/min). Pulmonary function tests [forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and peak expiratory flow (PEF)] were performed and the percentages of predicted values were calculated (%FEV(1), %FVC and %PEF). Systemic inflammation, assessed by high-sensitivity C-reactive protein (hsCRP) and nutritional status assessed by subjective global assessment (SGA), lean body mass (LBM) (estimated with dual energy X-ray absorptiometry) and hand-grip strength (HGS), were evaluated at the same time. RESULTS: Significant negative correlations were found between hsCRP and the percent predicted values for all pulmonary function tests [%FEV(1) (Rho = -0.45), %FVC (Rho = -0.43) and %PEF (Rho = -0.38)], respectively. Malnourished patients defined as SGA >or=2 had lower %FEV(1) (64+/-19 vs 82+/-23%; P<0.001) and %FVC (67+/-18 vs 83+/-21%; P<0.001) than well nourished patients. Significant correlations were observed between HGS and %FVC (Rho = 0.38; P <0.001), %FEV(1) (Rho = 0.37; P<0.001) and %PEF (Rho = 0.22; P<0.05) and between LBM and %PEF (Rho = 0.20; P<0.05). Multivariate Cox analysis showed that cardiovascular disease and low %FVC were associated with poor survival. CONCLUSIONS: Impaired pulmonary function is associated with malnutrition and inflammation, and predicts mortality in CKD patients. This may reflect an impact of malnutrition and inflammation on respiratory muscle performance, leading to pulmonary dysfunction, which could influence the clinical outcome.     

维持性血液透析患者内瘘血流量与炎性反应状态的关系及对心血管病的影响

目的 探讨维持性血液透析(MHD)患者内瘘血流量与炎性反应状态的关系及其对心血管病(CVD)的影响.方法 30例以自体动静脉内瘘(AVF)为透析通路的MHD患者(MHD组)及12例健康体检者(对照组)入选本研究.Transonic HD 02透析监测仪监测内瘘血流量(Qa)和心输出量(C0).MHD组在监测Qa前取透前血标本,对照组标本来自我院健康体检人群.用免疫透射比浊法检测高敏C反应蛋白(hsCRP);用流式细胞仪的液相蛋白定量技术检测炎性因子白细胞介素(IL)2、IL-6、IL-10、肿瘤坏死因子(TNF).随访时间19个月,记录发病情况.结果 两组年龄及性别差异无统计学意义.MHD组透前IL-6、IL-10、TNF、hsCRP均显著高于对照组[2.38( 1.86 ～4.69)比1.14(0.27～1.18) ng/L,P＜0.01;1.47(1.19～2.10)比1.04 (0.00～1.23) ng/L,P＜0.01;1.33(1.05～1.56)比0.54(0.00～1.24) ng/L,P＜0.05;4.90( 1.58～7.45)比1.50( 0.63～1.90) mg/L,P=0.01].随访期间,6例(20.0％)患者至少发生1次心血管病.发生心血管病者Qa、IL-6、hsCRP均显著高于未发病者[(1120±192)比(893±189) ml/min,P＜0.05;4.86 (2.96～7.85)比2.20 (1.80～3.10) ng/L,P＜0.01;11.75(3.83～31.53)比4.45(1.05～6.68) mg/L,P＜0.05].二元Logistic回归分析显示,IL-6为CVD的独立危险因素(HR=1.943,95％CI:1.110～3.402,P=0.02).Spearman相关分析及线性回归分析显示,Qa与IL-6呈正相关(β=0.492,P＜0.01).路径分析结果显示,Qa通过IL-6对CVD有间接的显著影响.结论 IL-6是CVD发生的独立危险因素.Qa与IL-6呈正相关.Qa可通过影响MHD患者IL-6水平参与了CVD的发生.