Correlation between cathepsin D serum concentration and carotid intima-media thickness in hemodialysis patients

Aim  

Cardiovascular (CV) disease is the leading cause of death in hemodialysis (HD) patients, and approximately half of mortalities in HD patients are attributed to CV disease. Atherosclerosis is the most frequent cause of CV complications in patients with end-stage renal disease (ESRD). Based on recent studies, cathepsin D has been suggested as a potential marker of atherosclerosis, and we hypothesized that there is an association between serum concentration of cathepsin D and carotid intima-media thickness (CIMT) in hemodialysis patients.     

Serum alkaline phosphatase levels associate with elevated serum C-reactive protein in chronic kidney disease

High serum alkaline phosphatase concentrations are associated with elevated serum C-reactive protein (CRP) levels in the general population. To examine whether this association is independent of serum vitamin D levels or modified in chronic kidney disease (CKD), we determined if such associations exist using data from the National Health and Nutrition Examination Survey III of 14,420 adult participants in which 5.7% had CKD (defined as estimated glomerular filtration rate < 60 ml/min per 1.73 m2). For each doubling of serum alkaline phosphatase, the odds of elevated serum CRP (over 3 mg/l) were increased 2.73-fold in the non-chronic and 2.50-fold in the CKD sub-populations, respectively. Regression coefficients of each doubling of serum alkaline phosphatase with elevated CRP were not significantly different in between the sub-populations. Additional adjustment for the serum 25-hydroxy (OH) vitamin D level did not substantively change the results. Thus, associations of serum alkaline phosphatase with elevated CRP are independent of serum 25-OH vitamin D in the chronic and non-CKD populations. Hence, serum alkaline phosphatase might be a marker of the inflammatory milieu.     

Relationship between insulin resistance and increased carotid artery intima-media thickness in non-diabetic kidney disease patients

Objective To evaluate the relationship of insulin resistance (IR) and carotid artery intima-media thickness (CA-IMT), plaque status in non-diabetic non-dialysis chronic kidney disease (CKD) patients with different stages. Methods One hundred and seventeen non-diabetes non-dialysis CKD patients were enrolled into this cross-sectional observational study. Insulin resistance index (HOME-IR) was assessed by the homeostasis model assessment. Patients with HOME-IR≥1.73 were defined as insulin resistance. And patients with CA-IMT≥0.9 mm were defined as thickening. The blood pressure measurement, heart Doppler ultrasound, bilateral carotid artery ultrasound examination, blood biochemistry and urine protein test were performed, eGFR was calculated by EPI formula. Results The prevalence of IR was 47.01% in 117 non-diabetic non-dialysis CKD patients, and it was 35.71%, 50.00% and 54.55% in eGFR≥60ml•min-1•(1.73 m2)-1 group, 30≤eGFR＜60ml•min-1•(1.73 m2)-1 group, and eGFR＜30ml•min-1•(1.73 m2)-1 group separately. In eGFR＜30ml•min-1•(1.73 m2)-1 group, cystain C, homocysteine, parathyroid hormone, Scr, BUN, uric acid, interventricular septal thickness, left ventricular dimension, left ventricular posterior wall thickness were significantly higher than that in the other two groups (P＜0.01), while the level of hemoglobin was significantly lower (P＜0.01); then the levels of serum albumin and systolic pressure were higher than that in the eGFR≥60ml•min-1•(1.73 m2)-1 group, however, the levels of total cholesterol and low-density lipoprotein-cholesterol were lower than that in the eGFR≥60ml•min-1•(1.73 m2)-1 group. Correlation analysis showed that insulin resistance index was significantly correlated with CA-IMT (r=0.444, P=0.006）in the eGFR＜30ml•min-1•(1.73 m2)-1 group, however, there wasn’t correlation in other two groups. And although insulin resistance wasn’t correlated with soft plaque, it was significantly correlated with hard plaque (χ2=6.476, P=0.011) in the eGFR＜30ml•min-1•(1.73 m2)-1 group. The Logistic regression analysis results displayed aging increase was the independent risk factor of the CA-IMT thickening for non-diabetes non-dialysis CKD patients but not insulin resistance. Conclusions HOMA-IR is correlated with CA-IMT and hard plaque when eGFR＜30ml•min-1•(1.73 m2)-1 in non-diabetes non-dialysis CKD patients. However, the insulin resistance isn’t the independent risk factor of the CA-IMT thickening for non-diabetes non-dialysis CKD patients.     

Dyslipidemia,carotid intima-media thickness and endothelial dysfunction in children with chronic kidney disease

Background

Chronic kidney disease (CKD) predisposes to accelerated atherosclerosis that is measured by carotid artery intima-media thickness (cIMT) and brachial artery flow-mediated dilation (FMD). Information on the association of these parameters with dyslipidemia in pre-dialysis pediatric CKD is limited.

Methods

Eighty patients aged 9.9?±?3.2 years, with estimated glomerular filtration rate of 38.8?±?10.8 ml/1.73 m²/min, and 42 pediatric controls underwent cross-sectional analysis of lipid profile, cIMT, and brachial artery FMD. Significant differences in these parameters between patients and controls were analyzed using Student’s t test. Predictors of cIMT and dyslipidemia were assessed using linear and logistic regression respectively.

Results

Patients had elevated blood levels of triglyceride and of total and LDL cholesterol than controls (P?≤?0.001); 73.8 % were dyslipidemic. Mean cIMT was higher (0.421?±?0.054 mm vs 0.388?±?0.036 mm, P?=?0.001) and brachial artery FMD was reduced (10.6?±?4.9 % vs 18.9?±?4.1 %, P?<?0.0001) in patients compared with controls. On multivariate analysis, hypertension (OR 3.68, P?=?0.044) and male gender (OR 10.21, P?=?0.004) were associated with dyslipidemia; cIMT was significantly associated with LDL cholesterol (β?=?28.36, P?=?0.033).

Conclusion

Dyslipidemia was prevalent and cIMT significantly elevated in pre-dialysis pediatric CKD, indicating increased cardiovascular risk. Elevated LDL cholesterol predicted increased cIMT, strengthening the association between dyslipidemia and atherosclerosis in early CKD.

     

Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase that has been linked to endothelial dysfunction and atherosclerosis in the general population. ADMA is also elevated in end-stage renal disease and may contribute to the high cardiovascular risk in patients with chronic renal failure. A prospective cohort study was performed to investigate the relationship between plasma ADMA, C-reactive protein (CRP), and intima-media thickness (IMT) in 90 patients undergoing hemodialysis. In the baseline study, plasma ADMA was directly related to IMT both on univariate analysis (r = 0.32, P = 0.002) and on multiple regression analysis (beta = 0.23, P = 0.01). In the follow-up study (15 mo) IMT changes were significantly related to ADMA (r = 0.51, P = 0.02) and serum CRP (r = 0.53, P = 0.01) in patients with initially normal IMT. In these patients, ADMA and CRP were strongly interrelated (r = 0.64, P = 0.002), and on multiple regression analysis the interaction between ADMA and CRP emerged as the sole independent predictor of the progression of intimal lesions. Independently of other risk factors, plasma ADMA in patients on hemodialysis is significantly related to IMT. Furthermore, in patients with initially normal IMT, ADMA and CRP are interacting factors in the progression of carotid intimal lesions. These data support the hypothesis that accumulation of this endogenous inhibitor of NO synthase is an important risk factor for cardiovascular disease in chronic renal failure and suggest a possible link between ADMA and inflammation.     

2型糖尿病兼或有肾脏病者颈总动脉内中膜厚度与血清淀粉样蛋白A水平的关系

目的探讨2型糖尿病肾脏病患者颈总动脉内中膜厚度（CCA-IMT）与血清淀粉样蛋白A（SAA）水平的相关关系。方法2型糖尿病患者107例,依据尿蛋白排泄率（UAER）结果分为单纯糖尿病组（SDM组）38例：UAER〈30mg／24h;糖尿病肾脏病组（DKD组）69例：UAER≥30mg／24h。DKD组依据肾小球滤过率（GFR）水平分为2组,DKD早中期组34例：GFR〉30ml／min;DKD中晚期组35例：GFR≤30ml／min。测定血清SAA及CCA-IMT水平,进行多因素分析。结果DKD组SAA水平、CCA-IMT较SDM组高;DKD中晚期组SAA水平、CCA-IMT较SDM组、DKD早中期组升高。SAA水平与腰臀比、CAEA-IMT、三酰甘油呈正相关;年龄、SAA及UAER是影响CCA-IMT的相关因素。结论2型糖尿病肾脏病患者血清SAA明显升高,并与CCA-IMT密切相关。     

维持性血透患者颈动脉内膜中层厚度增厚及其影响因素分析

目的研究维持性血透(MHD)患者颈动脉内膜中层厚度(IMT)增厚情况并分析其可能影响因素。方法75例MHD患者为MHD组,30例健康体检者为对照组。采用高频B超检测其颈动脉IMT值,并记录各患者的临床及生化数据。MHD组按IMT值分为正常、异常和增厚3个亚组。对各组数据进行比较并对IMT的各危险因素进行相关性分析。结果MHD组患者颈动脉IMT值明显大于对照组[(1.03±0.42)比(0.63±0.11)mm,P<0.01]。IMT增厚组年龄、收缩压、血浆白蛋白、前白蛋白、胆固醇、血磷水平与IMT正常组相比,差异有统计学意义(P<0.05或P<0.01)。IMT异常组的收缩压、血磷水平明显高于IMT正常组(P<0.01)。单因素相关分析(Model1)结果显示,MHD患者颈动脉IMT与年龄(r=0.247,P=0.032)、收缩压(r=0.758,P<0.01)、血磷(r=0.604,P<0.01)呈显著正相关;与血浆白蛋白(r=-0.292,P=0.011)、前白蛋白(r=-0.681,P<0.01)呈显著负相关。经控制年龄因素后的偏相关分析(Model2)结果与Model1结果一致。多元线性回归分析结果显示高收缩压(B=0.446,P<0.01)、低前白蛋白(β=-0.336,P<0.01)和高血磷(β=0.248,P=0.01)是颈动脉IMT增厚的独立影响因素。结论MHD患者颈动脉IMT明显增厚。高收缩压、低前白蛋白及高血磷是颈动脉IMT增厚的独立危险因素并可能与MHD患者动脉粥样硬化进展相关。     

Fibroblast growth factor-23 is associated with C-reactive protein, serum phosphate and bone mineral density in chronic kidney disease

Summary  

We investigated the association between fibroblast growth factor-23 (FGF-23) and (1) the biochemical parameters implicated in chronic kidney disorder (CKD)-bone and mineral disorder (CKD-MBD) and (2) bone mineral density (BMD) in patients with CKD 1-4. C-reactive protein (CRP) and serum phosphate correlated with FGF-23. A significant association was seen between FGF-23 and BMD at the hip.     

Evaluation of association between intima-media thickness of the carotid artery and risk factors for cardiovascular disease in patients on maintenance hemodialysis

Cardiovascular disease is the most common cause of mortality and morbidity in patients with end-stage renal disease (ESRD). Atherosclerosis is a systemic disease, and carotid and coronary vessels are at comparable risk for developing pathologic changes. For this reason, increase in the thickness of the intima-media layers of carotid arteries can be a harbinger of coronary atherosclerosis and also a prognostic factor for cardiovascular accidents. In this study, we evaluated the status of carotid intima-media thickness (CIMT) in patients with ESRD on dialysis and analyzed its association with other risk factors for cardiovascular diseases. This cross-sectional study was conducted on patients referred for hemodialysis (HD) to the Taleghani Hospital (Shahid Beheshti University of Medical Sciences, Tehran, Iran) during 2007-2008. At the beginning, biochemical parameters and common cardiovascular risk factors were extracted from the patients' files, and then CIMT was measured by using B-Mode high-resolution ultrasonography, 1 cm proximal to the carotid bulb in the posterior wall. Finally, correlation between other risk factors and CIMT was made. One hundred patients with chronic and advanced renal disease were evaluated, including 46% females and 54% males. The mean age of these patients was 59.2 ± 13.1 years, with a range of 26-81 years. Correlations between CIMT and age (P = 0.023, r = 0.478), dialysis duration (P = 0.017, r = 0.435), number of cigarettes smoked (P = 0.026, r = 0.429), diastolic blood pressure (P = 0.013, r = 0.455) and fasting blood sugar (P = 0.045, r = 0.346) were significant. Risk factors for cardiovascular disease in patients on HD are of significant interest because of the high prevalence and frequency of the disease in this group of patients. However, in the present study, we were not able to find a very consistent and definite role for some risk factors in our patients. More studies are required to make clear the role of these factors in patients on HD.     

血液透析患者血8-羟基脱氧鸟苷与血管内皮功能、颈动脉内膜中层厚度的关系

目的检测血液透析(hemodialysis,HD)患者血8-羟基脱氧鸟苷(8-hydroxydeoxyguanosine,8-OHdG)、血内皮素1(endothelinm-1,ET-1)、内皮型一氧化氮合酶(endotheliat nitric oxide synthase,eNOS)水平及颈动脉内膜中层厚度,探讨氧化应激在HD患者血管内皮功能障碍、动脉粥样硬化中的作用。方法选择2014年10月至2015年4月在河北省迁安市人民医院行血液透析治疗3个月以上的非糖尿病尿毒症患者52例为HD组;另设本院体检健康者45例为对照组。采用ELISA法测定血8-OHdG浓度,放射免疫法测定血ET-1含量,硝酸酶还原法进行血eNOS活力测定。采用多普勒超声检测颈动脉内膜中层厚度(carotid intimal-medial thickness,CIMT)。结果与对照组比较,HD组患者CIMT明显增厚[(1.31±0.29)mTmrn比(0.82±0.21)rm,P0.013。HD组患者动脉硬化的发生率为78.85%。与对照组比较,HD组患者血8-OHdG水平明显升高[(38.30±9.34)ng/ml比(7.24±0.87)ng/ml,P0.01);HD组患者血ET-1水平明显升高[(138.35±31.12)pg/ml比(16.40±1.21)pg/ml,P0.01];HD组患者血eNOS水平降低[(12.67±1.66)U/ml比(14.05±1.56)U/ml,P0.013。HD组患者血8-OHdG水平与年龄、透析时间、超敏C反应蛋白(high sensitivity C-reactive protein,hs-CRP)、收缩压、舒张压、ET-1呈正相关(r=0.697、0.752、0.532、0.350、0.269、0.753,P0.05),与尿素清除指数(Kt/V)、eNOS呈负相关(r=-0.367、-0.723,P0.01)。多元线性逐步回归分析,显示血8-OHdG水平是HD患者CIMT的独立危险因素(B=0.044,P=0.001)。结论 HD患者存在明显的氧化应激状态和血管内皮功能障碍。HD患者的氧化应激参与了血管内皮功能障碍的发生。血8-OHdG水平是HD患者动脉粥样硬化的独立危险因素。     

Factors associated with serum leptin in patients with chronic kidney disease

BACKGROUND AND AIMS: Serum leptin levels are elevated in patients with kidney failure. Data on the associations of serum leptin and on the relationship of leptin with both kidney function and inflammation, are limited in patients with reduced glomerular filtration rate (GFR). We evaluated the independent associations of serum leptin in patients with reduced GFR. MATERIAL AND METHODS: Serum leptin and C-reactive protein (CRP) were measured in samples from 798 participants of the Modification of Diet in Renal Disease Study. Multivariable analysis was used to evaluate the independent effects of kidney function and CRP on leptin levels. RESULTS: Median (interquartile range) of serum leptin was 9.1 ng/ml (14.0). Female gender, higher percent body fat, higher insulin levels, older age, lower GFR and higher CRP were associated with higher serum leptin levels and explained 51% of the variability in the logarithm of serum leptin levels. After adjusting for the other variables, a 10 ml/min/1.73 m2 lower GFR was associated with 6% higher mean serum leptin levels. Percent body fat and gender, explained 45% of the variability in serum leptin levels. CONCLUSIONS: Level of kidney function and CRP are associated with serum leptin in patients with reduced GFR. However, there is a stronger association between serum leptin and indices of body fat and gender in patients in the earlier stages of chronic kidney disease. 50% of the variability remains unexplained in patients with reduced GFR.     

Relationship between carotid artery intima-media thickness and renal function in patients with diabetes mellitus

Objective To investigate the relationship between carotid artery intima-media thickness and renal function in patients with diabetes mellitus. Methods 424 patients of type 2 diabetes without dialysis were enrolled in a cross-sectional study. According to their artery intima-media thickness (IMT), the patients were divided into normal group and higher IMT group. All patients according to UAER or 24h urinary protein were divided into normal proteinuria group, micro-proteinuria group and clinical proteinuria group. The biochemical examination, eGFR, and atherosclerotic plaque of different groups were compared. Pearson or spearman correlation was used to analyze the relationship between eGFR, IMT and other parameters. Risk factors for eGFR decline were analyzed by binary logistic regression. Results Compared with normal group, patients in the higher IMT group were older [(63.3±10.2) year vs (52.5±10.6) year, P﹤0.05], and underwent longer duration of diabetes [(8.9±6.7) year vs (6.2±5.7) year, P﹤0.05]. Their level of eGFR was decreased [(75.92±28.00) ml/min vs (91.64±24.05) ml/min, P﹤0.05], while plaque incidence (71.3% vs 18.3%,χ2=112.42, P﹤0.01) and prevalence of hypertension (56.4% vs 29.6%, χ2=27.22, P﹤0.01) increased. Correlation analysis showed that IMT was positively correlated with age (r=0.503, P﹤0.01), duration of diabetes (r=0.204, P﹤0.01), 24 h urine protein (rs=0.175, P﹤0.05), plaque (rs=0.562, P﹤0.01), and hypertension (rs=0.193, P﹤0.01), but negatively correlated with eGFR (r=-0.307, P﹤0.01). Logistic regression analysis showed that age, serum uric acid, 24 h urine protein and carotid artery intima-media thickness were independent risk factors for eGFR decline [OR=1.115, 95%CI(1.053, 1.165), P﹤0.001; OR=1.008,95%CI (1.002, 1.014), P=0.006; OR=1.492, 95%CI(1.170,1.903), P=0.001; OR=1.619, 95%CI(1.121, 2.339), P=0.010]. Conclusion Carotid artery intima-media thickness is an independent risk factor for kidney function decline in patients of diabetes.     

Quotidian hemodialysis and inflammation associated with chronic kidney disease

The mortality rate of chronic dialysis patients in the United States is 24% per year per the 2006 United States Renal Data System. Although there have been marked improvements in dialysis technology, cardiovascular disease is the principal cause of mortality in end-stage renal disease patients. Inflammation and left ventricular hypertrophy both contribute to atherosclerosis. Hemodialysis 3 times a week is the most commonly used form of dialysis in the United States. The multicenter hemodialysis (HEMO) study hypothesized that an increase in dialysis dose and use of high-flux membranes would improve mortality and decrease morbidity. This study failed to show decreases in mortality. In other studies, however, there appears to be improved morbidity with more frequent dialysis including daily nocturnal hemodialysis and short-daily hemodialysis. The more frequent dialysis may have some beneficial effect on the inflammatory process that occurs in end-stage renal disease.     

慢性肾脏疾病患者颈动脉粥样斑块的相关因素分析

目的分析慢性肾脏疾病（chronickidneydisease,CKD）2～4期患者颈动脉粥样斑块发生情况及影响因素。方法收集湖北省中医院门诊及住院的142例CKD2～4期患者,根据颈动脉彩超检查结果是否有颈动脉斑块将其分为颈动脉斑块组（52例）及无颈动脉斑块组（90例）,记录患者的一般资料包括性别、年龄、体质量指数（bodymassindex,BMI）、昼夜平均收缩压（24hSBP）、昼夜平均舒张压（24hDBP）、高血压病史及糖尿病病史,检测所有患者血肌酐（SCr）以及估算肾小球滤过率（estimatedglomerularfiltrationrate,eGFR）、总胆固醇（totalcholesterol,TC）、三酰甘油（triglyceride,TG）、高密度脂蛋白胆固醇（highdensitylipoproteincholesterol,HDL-C）、低密度脂蛋白胆固醇（10wdensitylipoproteincholesterol,LDL-C）、糖化血红蛋白（glycosylatedhemoglobin,HbAlc）、超敏C反应蛋白（highsensitivec-reactiveprotein,Hs—CRP）、空腹血糖的水平,评估颈动脉斑块的发病率及其相关影响因素。结果颈动脉斑块组和无颈动脉斑块组2组问进行比较,其中年龄、HbAlc水平有显著统计学差异,eGFR、SBP、HDL-C水平、高血压、糖尿病有统计学差异,与性别、DBP、BMI及其余生化指标水平无关。以颈动脉斑块为因变量,将年龄、HbAlC、HDL-C、eGFR、糖尿病及高血压5项因素进行Logistic相关性分析,结果显示年龄与颈动脉斑块有统计学差异。结论本研究中,HbAlc、HDL-C、糖尿病、高血压、CKD及收缩压是颈动脉斑块发生的危险因素,高龄患者发生颈动脉斑块的可能性更大。     

Carotid intima media thickness is independently associated with urinary sodium excretion in patients with chronic kidney disease

Abstract

Atherosclerosis-induced premature vascular diseases are the leading cause of mortality among patients with chronic kidney disease (CKD). The pathogenetic mechanism of atherosclerosis in patients with CKD has not been fully explained. Experimental studies have demonstrated that high dietary sodium intake not only increases circulatory volume and blood pressure, but also facilitates development of atherosclerosis by reducing production-bioavailability of nitric oxide due to oxidative stress and accordingly by enhancing endothelial and arterial stiffness. In this study, we investigated the relationship between sodium consumption and carotid artery intima-media thickness, which is the indicator of atherosclerosis, by determining daily urinary sodium excretion, which is a reliable indicator of sodium consumption, in our patient group. Our patient group included 193 patients with stage 2–4 non-diabetic CKD and without a history of atherosclerotic disease. We determined that 77% of our patients have been consuming more than 2 g of sodium per day, which is the upper limit of sodium consumption recommended for patients with CKD. We determined a positive linear correlation between carotid artery intima-media thickness and patient age (p?<?0.001), C-reactive protein (p?<?0.001), urinary sodium excretion (p?<?0.001), body mass index (p?=?0.002), systolic blood pressure (p?=?0.002), hemoglobin (p?=?0.030), triglycerides (p?=?0.043), and diastolic blood pressure (p?=?0.049). We also found a negative linear correlation between carotid artery intima-media thickness and glomerular filtration rate (p?=?0.008). We found that urinary sodium excretion is the determinant of intima-media thickness even if all factors associated with intima-media thickness are adjusted, and that intima-media thickness increases by 0.031 (0.004–0.059) mm per 2 g increase in daily sodium excretion, independent from overall factors (p?=?0.025). Our results reveal a relation between urinary sodium excretion and carotid artery intima-media thickness and suggest that excessive sodium consumption predisposes development of atherosclerosis in patients with CKD.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in peritoneal dialysis patients

Background and aim   Carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation percentage (FMD%) are two commonly used parameters for detecting subclinical atherosclerosis. However, studies investigating the relationship between CIMT and brachial artery FMD% in different populations have produced conflicting results. The aim of this study was to determine the relationship between CIMT and brachial artery FMD% in patients on peritoneal dialysis (PD) Methods   Fifty-two PD patients without known cardiovascular disease and 30 age-gender matched controls were included in the study. Endothelial function was determined using ultrasonography (US) to measure the FMD of the brachial artery, and this parameter was expressed as the percentage change from the baseline diameter of the brachial artery (FMD%). We also measured CIMT by US and analysed the relationship between CIMT and brachial FMD%. Results   The CIMT was significantly higher in patients than in the control group (0.84 ± 0.08 vs. 0.75 ± 0.06 mm, P < 0.01), whereas brachial artery FMD% was lower in patients than in the controls (8.2 ± 5.0 vs. 11.7 ± 5.5%, P < 0.01). There was no significant correlation between CIMT and FMD% (r = −0.004, P = 0.94). Conclusion  Although PD patients are known to be characterized by an impaired flow-mediated vasodilatation of brachial artery and increased in CIMT, we did not find a significant correlation between FMD% and CIMT in our PD patient cohort. One possible explanation for our results is that each method measures a different aspect and stage of atherosclerosis.