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。     

Glomerular endothelial dysfunction in chronic kidney disease

A dysfunctioning glomerular endothelium was demonstrated in chronic kidney disease (CKD) patients by means of in vitro endothelial cell cytotoxicity test and of in vivo intrarenal hemodynamic study. An enhanced endothelial cell cytotoxicity in CKD patients was 26.5 +/- 12% as compared to 0.4 +/- 1% of control. An altered intrarenal hemodynamics revealed 1) a reduction in renal plasma flow, 190 +/- 67 mL/min/1.73 m2 versus control 595 +/- 45 mL/min/1.73 m2, and in peritubular capillary flow, 149 +/- 55 mL/min/1.73 m2 versus control 479 +/- 46 mL/min/1.73 m2, 2) an elevated intraglomerular hydrostatic pressure, 55 +/- 2 mmHg versus control 51 mmHg, elevated afferent arteriolar resistance, 13184 dyne x s x cm(-5) versus control 2443 +/- 154 dyne x s x cm(5), and elevated efferent arteriolar resistance, 13591 +/- 7591 dyne x s x cm(-5) versus control 3062 +/- 177 dyne x s x cm(-5). Both enhanced endothelial cell cytotoxicity and altered intrarenal hemodynamics reflect glomerular endothelial dysfunction which is likely responsible for the renal disease progression in CKD.     

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.     

Hyperlipidemia, oxidative stress, and intima media thickness in children with chronic kidney disease

Background

The roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis.

Methods

Fifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS).

Results

Children with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, μmol/L]: CRF 1.50?±?0.26, RT 1.55?±?0.40, cHD 1.77?±?0.34, CG 0.97?±?0.33, p?<?0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120?±?21, CRF 84?±?25, RT 93?±?12, cHD 119?±?37, p?<?0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS.

Conclusions

Early atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase.     

Serum visfatin concentration and endothelial dysfunction in chronic kidney disease.

BACKGROUND: Endothelial dysfunction (ED) is common in patients with moderate to advanced chronic kidney disease (CKD). Recently, visfatin, a protein with insulin-mimetic properties, was shown to be associated with sVCAM-1. Thus, we hypothesised that visfatin may be a marker of ED in CKD. METHODS: We studied 406 patients with different stages of non-diabetic CKD (50% males, 46 +/- 12 years), testing the relationship between flow-mediated dilatation (FMD), assessed by high resolution brachial ultrasonography, and plasma adiponectin and visfatin concentrations. Eighty healthy volunteers (50% males, 46 +/- 11 years) served as matched controls. RESULTS: Compared to healthy controls, ED was observed in all stages of CKD (Stages 1-5) and correlated strongly with the reduction in estimated glomerular filtration rate (eGFR). Whereas visfatin concentrations were found to be increased in all but CKD stages 1 and 2, adiponectin levels were found to be increased in all patients but CKD stage 1. Visfatin and adiponectin levels were strongly correlated with eGFR (rho = -0.62 and rho = -0.72, respectively, P < 0.001 for both). FMD levels were negatively correlated with both visfatin and adiponectin levels (rho = -0.53 and, rho = -0.57, respectively, P < 0.001 for both). In a multiple regression model, eGFR levels (Beta = 0.74, P < 0.001), visfatin (Beta = -0.15, P < 0.001), age (Beta = 0.06, P < 0.01), adiponectin (Beta = 0.09, P < 0.05), HOMA-IR (Beta = 0.07, P < 0.05) and hsCRP (Beta = -0.08, P < 0.05) were all found to be significantly related to FMD. CONCLUSIONS: We conclude that the circulating levels of visfatin and adiponectin are associated with ED in all stages of CKD, independently of inflammation and insulin resistance.     

Chronic periodontitis in hemodialysis patients with chronic kidney disease is associated with elevated serum C-reactive protein concentration and greater intima-media thickness of the carotid artery

BACKGROUND: An increasing number of papers have documented the contribution of chronic periodontitis (P) to the pathogenesis of cardiovascular disease. The aim of this study was to answer the question whether there is an association between periodontal inflammation and atherosclerotic processes in hemodialysis patients with chronic kidney disease (CKD). METHODS: Forty-four hemodialysis patients with CKD were considered. Advanced chronic periodontitis was found in 17, whereas 27 patients had no or moderate chronic periodontitis. In all patients examined, serum C-reactive protein (CRP), TNF-alfa and IL-6 concentrations, as well as intima-media thickness (IMT) of the carotid artery, were assessed. RESULTS: Patients with CKD and advanced periodontitis were characterized by a significantly higher serum CRP concentration (13.2 +/- 11.4 vs. 10.4 +/- 14.4; p<0.05) and IMT (0.742 +/- 0.028 vs. 0.656 +/- 0.019, p<0.05) than CKD patients without periodontitis. In the univariate analysis, a significant correlation between CRP and number of atherosclerotic plaques was revealed; however, it was not confirmed as an independent relationship in the multiple regression analysis. CONCLUSIONS: Inflammation of the periodontal tissue in patients with CKD is associated with increased serum CRP concentration and greater IMT. It is possible that periodontitis may induce a systemic process that may exacerbate atherosclerosis.     

Carotid intima media thickness, oxidative stress, and inflammation in children with chronic kidney disease

Objective

We evaluated the association between inflammation and oxidative stress with carotid intima media thickness (cIMT) and elasticity increment module (E_inc) in pediatric patients with chronic kidney disease (CKD).

Methods

This analytical, cross-sectional study assessed 134 children aged 6–17 years with CKD. Anthropometric measurements and biochemistry of intact parathyroid hormone (iPTH), high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-1β, reduced glutathione (GSH), malondialdehyde, nitric oxide, and homocysteine were recorded. Bilateral carotid ultrasound (US) was taken. Patients were compared with controls for cIMT and E_inc using?≥?75  percentile (PC).

Results

Mean cIMT was 0.528?±?0.089 mm; E_inc was 0.174?±?0.121 kPa × 10³; cIMT negatively correlated with phosphorus (r ?0.19, p?=?0.028) and the calcium × phosphorus (Ca × P) product (r ?0.26, p?=?0.002), and positively with iPTH (r 0.19,p?=?0.024). After adjusting for potential confounders, hemodialysis (HD) (β?=?0.111, p?=?<0.001), automated peritoneal dialysis (APD) (β?=?0.064, p?=?0.026), and Ca x P product (β?=??0.002, p?=?0.015) predicted cIMT (R ²?=?0.296). In patients on dialysis, HD (β?=?0.068, p?=?0.010), low-density lipoprotein cholesterol (LDL-C) (β?=?0.001, p?=?0.048), and GSH (β?=??0.0001, p?=?0.041) independently predicted cIMT (R ²?=?0.204); HD, hypoalbuminemia, and high iPTH increased the risk of increased cIMT. In dialysis, E_inc was inversely associated with GSH, and in predialysis, Ca × P correlated with/predicted E_inc (β?=?0.001, p?=?0.009).

Conclusions

cIMT and E_inc strongly associate with several biochemical parameters and GSH but not with other oxidative stress or inflammation markers.     

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease

Purpose

Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients.

Materials and methods

Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied.

Results

There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (β = ? 0.548, P < 0.001) and lower levels of 25(OH)D (β = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001).

Conclusions

Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

     

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.     

Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease

Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD and LVH. We randomly assigned 67 subjects to allopurinol at 300 mg/d or placebo for 9 months; 53 patients completed the study. We measured left ventricular mass index (LVMI) with cardiac magnetic resonance imaging (MRI), assessed endothelial function by flow-mediated dilation (FMD) of the brachial artery, and evaluated central arterial stiffness by pulse-wave analysis. Allopurinol significantly reduced LVH (P=0.036), improved endothelial function (P=0.009), and improved the central augmentation index (P=0.015). This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD. Because LVH and endothelial dysfunction associate with prognosis, these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH.     

Sexual dysfunction in men and women with chronic kidney disease and end-stage kidney disease

Sexual dysfunction is a common finding in both men and women with chronic kidney failure. Common disturbances include erectile dysfunction in men, menstrual abnormalities in women, and decreased libido and fertility in both sexes. These abnormalities are primarily organic in nature and are related to uremia as well as the other comorbid conditions that frequently occur in the chronic kidney failure patient. Fatigue and psychosocial factors related to the presence of a chronic disease are also contributory factors. Disturbances in the hypothalamic-pituitary-gonadal axis can be detected before the need for dialysis but continue to worsen once dialytic therapy is initiated. Impaired gonadal function is prominent in uremic men, whereas the disturbances in the hypothalamic-pituitary axis are more subtle. By contrast, central disturbances are more prominent in uremic women. Therapy is initially directed toward optimizing the delivery of dialysis, correcting anemia with recombinant erythropoietin, and controlling the degree of secondary hyperparathyroidism with vitamin D. For many practicing nephrologists, sildenafil has become the first line therapy in the treatment of impotence. In the hypogonadal man whose only complaint is decreased libido, testosterone may be of benefit. Regular gynecologic follow-up is required in uremic women to guard against potential complications of unopposed estrogen effect. Uremic women should be advised against pregnancy while on dialysis. Successful transplantation is the most effective means of restoring normal sexual function in both men and women with chronic kidney failure.     

Cardiovascular disease in children with chronic kidney disease

More than a decade ago, cardiovascular disease (CVD) was recognized as a major cause of death in children with advanced CKD. This observation has sparked the publication of multiple studies assessing cardiovascular risk, mechanisms of disease, and early markers of CVD in this population. Similar to adults, children with CKD have an extremely high prevalence of traditional and uremia-related CVD risk factors. Early markers of cardiomyopathy, such as left ventricular hypertrophy and dysfunction, and early markers of atherosclerosis, such as increased carotid artery intima-media thickness, carotid arterial wall stiffness, and coronary artery calcification, are frequently present in these children, especially those on maintenance dialysis. As a population without preexisting symptomatic cardiac disease, children with CKD potentially receive significant benefit from aggressive attempts to prevent and treat CVD. Early CKD, before needing dialysis, is the optimal time to both identify modifiable risk factors and intervene in an effort to avert future CVD. Slowing the progression of CKD, avoiding long-term dialysis and, if possible, conducting preemptive transplantation may represent the best strategies to decrease the risk of premature cardiac disease and death in children with CKD.     

Cardiovascular disease in children with chronic kidney disease

In children with end-stage renal disease (ESRD), cardiovascular disease (CVD) mortality has not changed for the past 3 decades. Cardiac disease remains the second most common cause of death. Recent data demonstrate a high incidence and prevalence of traditional and chronic kidney disease (CKD)-related CVD risk factors in children. Early markers of cardiomyopathy, such as left ventricular hypertrophy (LVH) and left ventricular dysfunction (LV dysfunction), and early markers of atherosclerosis, such as increased carotid artery intima-media thickness (IMT) and carotid arterial wall stiffness, are frequently found in this patient population. Early identification of modifiable risk factors and treatment of asymptomatic CVD might lead to decrease of cardiovascular morbidity and mortality in young adults who developed CKD during childhood.     

Hypertension in children with chronic kidney disease

Hypertension occurs commonly in children with chronic kidney disease (CKD) and undoubtedly contributes to the progression of disease. This review summarizes the role of hypertension in the progression of CKD in children and highlights the central role played by the renin-angiotensin system in this relentless process. Strategies for reno-protection are discussed, and treatment recommendations are made for control of hypertension in this patient population.     

Immunizations in children with chronic kidney disease

Children with chronic kidney disease (CKD) are at increased risk for vaccine-preventable diseases. These patients may have a reduced response to and/or reduced duration of antibody after immunization and therefore monitoring of antibody levels or titers is indicated for some vaccines. In addition, pediatric CKD patients require immunizations not routinely provided to healthy children. Unfortunately, studies in pediatric CKD patients, including those on dialysis and awaiting kidney transplantation, have demonstrated sub-optimal immunization rates. In order to minimize the risk for vaccine-preventable disease in pediatric CKD patients, it is imperative that all who care for these patients remain abreast of the recommended childhood immunization schedule, as well as alterations to this schedule required for children with CKD, including end-stage kidney disease. This article reviews recent changes to the recommended childhood immunization schedule and alterations and additions to this schedule recommended for children with CKD. Where available, data on antibody response to immunizations in children with CKD are presented.     

Anemia in children with chronic kidney disease

Anemia in children with chronic kidney disease (CKD) is common secondary to inadequate erythropoietin production, iron deficiency, blood loss, inflammation, secondary hyperparathyroidism, uremic toxins, and nutritional deficiencies. Anemia has a variety of deleterious consequences, including associations with increased mortality and left ventricular hypertrophy. Recombinant human erythropoietin is effective in treating anemia in children with CKD, and recent studies show that darbepoetin alpha is an attractive alternative because it requires less frequent injections. Iron deficiency is a major cause of anemia that is resistant to erythropoietin or darbepoetin alpha. Although oral iron is effective in some patients, many children, especially those receiving hemodialysis, require intravenous iron to replenish their iron stores. Both acute dosing and chronic dosing of intravenous iron are effective in pediatric patients.