Chronic inflammation in peritoneal dialysis: the search for the holy grail?

Mortality and morbidity in chronic kidney disease (CKD) patients are unacceptably high. The annual mortality rate due to cardiovascular disease (CVD) is approximately 9%, which, for the middle-aged person, is at least 10- to 20-fold higher than for the general population. Classic risk factors for CVD are highly prevalent in CKD patients, but they cannot fully account for the excessive rate of CVD in this population. Instead, it has become increasingly clear that nontraditional risk factors, such as systemic inflammation, may play a key role in the development of atherosclerosis. It is well established that inflammatory markers are very powerful predictors of high CVD morbidity and mortality not only in the general population, but particularly in CKD patients. Signs of a sustained low-grade inflammation, such as increased levels of C-reactive protein (CRP), are present in the majority of stage 5 CKD patients, even in patients in clinically stable condition, and they are also commonly observed after the initiation of dialysis therapy. Dialysis therapy--hemodialysis as well as peritoneal dialysis (PD)--may itself contribute to systemic inflammation. Local intraperitoneal inflammation can also occur in patients treated with PD. These local effects may result in a low-grade inflammation, caused by the bioincompatibility of conventional glucose-based dialysis fluids, to intense inflammation associated with peritonitis. Given these circumstances, it is reasonable to hypothesize that strategies aiming to reduce inflammation are potentially important and novel, and could serve to reduce CVD, thereby lowering morbidity and mortality in patients with CKD. In this review we provide information supporting the hypothesis that systemic inflammation is tightly linked to the most common complications of CKD patients, in particular those on PD, and that local inflammation in PD may contribute to various related complications. The aims of this review are to discuss the reasons that make inflammation an attractive target for intervention in CKD, the particular aspects of the inflammation-CVD axis during PD treatment that are likely involved, and possible means for the detection and management of chronic inflammation in PD patients.     

Chronic kidney disease and cardiovascular disease: a case presentation.

This is the third in a series of three articles examining cardiovascular disease (CVD) in the patient with chronic kidney disease (CKD). CVD is a leading cause of morbidity and mortality in patients with CKD, including those in the early stages. Early diagnosis of CKD and recognition of both traditional and nontraditional renal-related CVD risk factors are vital in improving outcomes for this population. Care of the patient with CKD should center on reduction of both types of risk factors for CVD. The ANNA Nephrology Nursing Standards of Practice and Guidelines for Care provide the basis for planning and providing care for patients with CKD and for reducing the risk of CVD in this patient population.     

Obesity and chronic kidney disease

Obesity and overweight are now characterized as epidemics. It is shown that body overweight is associated with functional and structural changes in the kidneys. The results of epidemiological studies indicate that obesity can be the risk factor of chronic kidney disease (CKD) irrespective of the presence or absence of diabetes, arterial hypertension and other comorbidities. Manifestations of renal pathology in obese persons include microalbuminuria and proteinuria, hyperfiltration or impaired renal function. Glomerulomegaly and focal segmental glomerulosclerosis are the most typical structural signs of obesity-related nephropathy. More evidence is accumulated on the link between CKD in obesity and abnormalities in adypokine secretion (hyperleptinemia, lack of adiponectin), activation of rennin-angiotensin system, chronic inflammation, endothelial dysfunction, lipid accumulation, impaired renal hemodynamics and diminished nephron number related to body mass. A decrease of body weight following lifestyle modification or bariatric surgery leads to reduction in albuminuria and eliminates hyperfiltration in obese subjects. Thus, prevention and treatment of obesity may reduce CKD incidence in general population.     

CKD非透析患者CVD的发生情况及影响因素分析

目的研究慢性肾脏病（CKD）非透析患心血管疾病（CVD）的发生情况及危险因素。方法分析695例cKD非透析患者基础资料、实验室指标、心脏彩色超声指标及其与既往CVD病史之间的关系,研究CKD非透析患者CVD的发生情况,探讨与其相关的危险因素。结果695例患者中226例（32．5％）有CVD既往史,Logistic回归分析显示,年龄、GFR、SBP、DBP、颈总动脉内径、颈总动脉IMT及分叉部IMT是cKD非透析患者CVD的独立危险因素。结论cKD非透析患者CVD的发生率较正常人显著升高,年龄、高血压、脂质代谢紊乱、微炎症状态、贫血、低蛋白血症、钙磷代谢紊乱等因素与CKD患者CVD的发生、发展密切相关。     

Cardiovascular Screening and Early Detection of Heart Disease in Adults With Chronic Kidney Disease

Cardiovascular disease (CVD) and chronic kidney disease (CKD) are among the most common disease states that nurse practitioners encounter in various health care settings. In many cases, patients with CVD and CKD have overlapping risk factors and underlying medical conditions. CVD is one of the most common causes of death in patients with CKD, and therefore, appropriate recognition and screening are important for preventing disease progression and complications. Nurse practitioners can become familiar with various risk factors, screen patients, and provide nonpharmacologic and pharmacologic measures for CVD in CKD patients.     

Chronic kidney disease (CKD) as an independent risk factor for cardiovascular disease (CVD)

Chronic kidney disease (CKD) has been shown to be an independent risk factor for cardiovascular disease (CVD) in a number of recent epidemiological studies. There are possible explanations for the independent association of CKD with CVD. Reduced renal function is associated with a high prevalence of traditional CVD risk factors, such as hypertension, diabetes, dyslipidemia, and left ventricular hypertrophy. In addition, reduced renal function may be associated with increased levels of nontraditional risk factors, such as inflammation and oxidative stress. Subjects with CKD should be considered a high-risk population for CVD and be recommended for more intensive preventive management of CVD, including active detection and strict treatment of CVD risk factors.     

Cardiovascular disease in chronic kidney disease: untying the Gordian knot

Chronic kidney disease (CKD) affects around 10–13% of the general population, with only a small proportion in end stage renal disease (ESRD), either on dialysis or awaiting renal transplantation. It is well documented that CKD patients have an extremely high risk of developing cardiovascular disease (CVD) compared with the general population, so much so that in the early stages of CKD patients are more likely to develop CVD than they are to progress to ESRD. Various pathophysiological pathways and explanations have been advanced and suggested to account for this, including endothelial dysfunction, dyslipidaemia, inflammation, left ventricular hypertrophy and cardiac autonomic dysfunction. In this review, we try to understand and further explore the link between CKD and CVD, as well as offering interventional advice where available, while exposing the current lack of RCT‐based research and trial evidence in this area. We also suggest pragmatic Interim measures we could take while we wait for definitive RCTs.     

Extra-skeletal effects of vitamin D deficiency in chronic kidney disease

Cardiovascular diseases (CVD) and infectious diseases represent the two most important causes of death in patients with chronic kidney disease (CKD). The traditional risk factors of CVD do not appear to account sufficiently for the increased risk of CVD in patients with CKD, and vitamin D deficiency appears to be an important non-traditional, and potentially modifiable, CVD risk factor in this patient population. 25-Hydroxyvitamin D (25(OH)D) is converted to its biologically active form, 1,25-dihydroxyvitamin D (1,25(OH)(2)D), by the enzyme 1α-hydroxylase in the kidneys. The recent discovery that many extrarenal tissues also possess both the 1α-hydroxylase enzyme and the vitamin D receptors has provided new insights into the important physiologic autocrine and paracrine roles of vitamin D in various tissues and organs that are mainly dependent on the availability of 25(OH)D from the circulating plasma. Accordingly, the present review focuses on the rapidly expanding body of clinical and experimental evidence that supports a strong association between 25(OH)D deficiency/insufficiency and the risk of adverse CVD outcomes and infectious diseases as well as on the non-calcemic autocrine and paracrine actions of vitamin D both in the general population and in patients with CKD.     

成纤维细胞生长因子23可预测慢性肾脏病中晚期患者冠状动脉钙化的发生及不良预后

目的探讨成纤维细胞生长因子23（fibroblast growth factor-23,FGF23）与慢性肾脏病（chronic kidney disease,CKD）患者冠状动脉钙化发生和预后的关系。方法入选2010年4月-12月上海交通大学医学院附属仁济医院肾脏科CKD非透析（CKD 3-5期）、腹膜透析和血液透析患者共150例,分析FGF23浓度与冠脉钙化的关系。并对这些患者进行为期（35±3）个月的随访,记录心血管和死亡事件。结果 CKD中晚期患者血清FGF23水平显著高于健康对照组（P〈0.01）。血清FGF23水平与冠脉钙化分数（CaS）之间呈显著正相关（r=0.177,P〈0.05）。Logistic回归分析显示年龄、透析龄和FGF23水平是CKD中晚期患者发生冠脉钙化的独立危险因素。Kaplan-Meier生存曲线提示FGF23水平较高的患者CVD发生率（P〈0.01）及全因死亡率（P〈0.05）显著高于FGF23水平较低的患者。Cox回归分析显示FGF23≥675.8pg/ml和冠脉明显钙化（冠脉CaS〉400）是患者发生CVD的独立危险因素。而FGF23水平和冠脉明显钙化（冠脉CaS〉400）是患者全因死亡的独立危险因素。结论 CKD中晚期患者的血清FGF23水平较普通人群显著增高,FGF23与CKD中晚期患者的冠脉钙化发生及不良预后可能相关。     

Utility of established cardiovascular disease risk score models for the 10-year prediction of disease outcomes in women

Cardiovascular disease (CVD) is a major cause of mortality globally. In absolute numbers, more women die from CVD than men do. CVD mortality risk differs between genders, reflecting the different distribution of modifiable risk factors and severity of CVD outcomes. This study reviews six established risk score models and their applicability to the female population. These models are assessed against two criteria: discrimination and calibration. Sensitivity, specificity and positive- and negative-predictive values are also examined. The risk score models are found to be limited in applicability, requiring recalibration beyond their study population. Relevant risk factors to predict CVD mortality for women, such as measures of obesity, physical activity, alcohol consumption, use of antihypertensive medication, chronic kidney disease and coronary artery calcium are generally not incorporated in these models.     

Overview of peritoneal dialysis in Latin America.

Latin America is a heterogeneous region comprised of 20 countries, former colonies of European countries, in which Latin-derived languages are spoken. According to the Latin American Society of Nephrology and Hypertension/Sociedad Latino Americana de Nefrologia e Hipertensión (SLANH), the acceptance rate for renal replacement therapy is 103 new patients per million population. In Latin America, hemodialysis is the predominant form of replacement therapy for end-stage renal disease; however, some countries employ peritoneal dialysis (PD) in 30% or more patients. In particular, Mexico is the country with the largest PD utilization in the world, and furthermore, it is estimated that approximately 25% of the world's PD population may be found Latin America. Data concerning clinical practice and long-term outcome of PD in Latin America are scarce, although regional registries are increasing in number and quality. In this review article, we present an overview of the situation of PD in several countries of Latin America, based on the registry of the SLANH, national registries, and personal communication with PD experts from different countries.     

Statins for treatment of dyslipidemia in chronic kidney disease.

Dyslipidemia is a potent cardiovascular (CV) risk factor in the general population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high-density lipoprotein (HDL-C) are well-established CV risk factors, but more precise determinants of risk include increased apoprotein B (ApoB), lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C, VLDL-C; "remnant particles"), and small dense LDL particles. Lipoprotein metabolism is altered in association with declining glomerular filtration rate such that patients with non dialysis-dependent chronic kidney disease (CKD) have lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C, and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are prevalent in hemodialysis (HD) patients, who often manifest proatherogenic changes in LDL-C in the absence of increased levels. Patients treated with peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to HD patients due to stimulation of hepatic lipoprotein synthesis by glucose absorption from dialysate, increased insulin levels, and selective protein loss in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent CKD population, total cholesterol is directly associated with increased mortality after controlling for the presence of malnutrition-inflammation. Treatment with statins reduces CV mortality in the general population by approximately one third, irrespective of baseline LDL-C or prior CV events. Statins have similar, if not greater, efficacy in altering the lipid profile in patients with dialysis-dependent CKD (HD and PD) compared to those with normal renal function, and are well tolerated in CKD patients at moderate doses (相似文献   

Insulin and insulin resistance: impact on blood pressure and cardiovascular disease

Cardiovascular disease is a major cause of mortality in individuals with diabetes. Many factors, including hypertension, contribute to the high prevalence of CVD in this population. Hypertension occurs approximately twice as frequently in patients with diabetes compared with patients without diabetes. Conversely, recent data suggest that hypertensive persons are more likely to develop diabetes than normotensive persons. In addition, up to 75% of CVD in patients with diabetes may be attributed to hypertension, leading to recommendations for more aggressive blood pressure control (ie, < 130/85 mm Hg) in persons with coexistent diabetes and hypertension. Increasing obesity further contributes to both diabetes and hypertension and significantly increases CVD morbidity and mortality. Other important risk factors for CVD in these patients include atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, coagulation abnormalities, and diabetic cardiomyopathy. The current knowledge regarding these risk factors has been reviewed, placing special emphasis on the metabolic syndrome, hypertension, microalbuminuria, and the role of obesity in these disorders. Although not discussed in detail, it is acknowledged that both hygienic measures (weight loss and aerobic exercise) and treatment strategies that include aspirin, statins, INS sensitizers, and antihypertensive agents that reduce renin-angiotensin-aldosterone system activity have been shown to reduce inflammation, coagulation abnormalities, endothelial function, proteinuria, and in some cases reduce CVD and renal disease progression. Additional therapeutic agents are currently being developed specifically to improve INS sensitivity and other CVD risk factors that are components of the cardiometabolic syndrome.     

Elevated serum levels of S-adenosylhomocysteine, but not homocysteine, are associated with cardiovascular disease in stage 5 chronic kidney disease patients

OBJECTIVE: The putative role of sulfur amino acids such as homocysteine (tHcy) as cardiovascular risk factors is controversial in chronic kidney disease (CKD). Although, S-adenosylhomocysteine (SAH) levels have been linked to CVD in non-renal populations, such relationship has not been evaluated in CKD. DESIGN: Serum concentrations of S-adenosylmethionine (SAM), SAH and total homocysteine (tHcy) were determined by HPLC in 124 CKD stage 5 patients (GFR range 1-11 m/min) and 47 control subjects, and related to renal function, presence of CVD, inflammation and protein-energy wasting (PEW). RESULTS: The levels of SAM and SAH were higher in CKD patients than in controls. Both SAM (rho=-0.19; P<0.05) and SAH (rho=-0.37, P<0.001) were inversely related to GFR. The concentrations of SAH were significantly higher (P<0.001) in patients with CVD than in non-CVD patients, (683 (201-3057) vs 485 (259-2620) nmol/L; median (range)) as opposed to tHcy levels, which were lower in CVD patients. While SAH was not associated with the presence of inflammation or PEW, it was a significant contributor (OR; 4.9 (CI 1.8-12.8), P<0.001) to CVD in a multinomial logistic regression model (pseudo r(2)=0.31). CONCLUSION: Concentrations of serum SAH and SAM in CKD stage 5 patients are associated with renal function, but not with inflammation or PEW. Among the investigated sulfur amino acids, only SAH was independently associated with the presence of clinical signs of CVD. These findings suggest that while tHcy might be influenced by a number of confounding uremic factors, SAH levels may better reflect the putative increased cardiovascular risk of sulfur amino acid alterations in CKD patients.     

Childhood obesity and risk of cardiovascular disease: a review of the science

Childhood obesity has been connected to hyperlipidemia, diabetes, hypertension, and atherosclerosis (Klish, 1998). Both genetic and environmental influences play a role in the development of obesity. Prevention of obesity in childhood is the best chance of instituting lifestyle change for the reduction of cardiovascular morbidity and mortality. Children at high risk for obesity-related cardiovascular disease (CVD) should receive family-based individualized treatment. Nurse practitioners practicing in the primary care setting are in an ideal position to address children and families with regard to lifestyle modification of diet and exercise.     

Cardiovascular disease and the kidney. Tracking a killer in chronic kidney disease

The interlinking of CVD with CKD is undeniable. CVD accounts for more than 50% of all morbidity and mortality in patients with kidney disease who have undergone renal replacement therapy, and CVD is also prevalent in patients with mild and moderately severe kidney disease. To help address the elevated risks of these patients, primary care physicians need to maintain vigilance in (1) identifying patients who have CKD and (2) implementing strategies for reducing the prevalence of CVD in this population. It is essential that patients be screened for relatively mild kidney disease by measurement of serum creatinine and urine microalbumin and by calculation of the glomerular filtration rate in mL/min/1.73 m2 using equations based on serum creatinine. Rigorous assessment of conventional risk factors, including dyslipidemia, hypertension, and diabetes, is also necessary to prevent the poor outcomes currently observed in persons with CKD. Routine use of ACE inhibitors and aspirin is encouraged in all patients with CKD, and strict glycemic and blood pressure control is recommended for optimal outcomes. In addition, patients should be screened and treated for risk factors particularly associated with kidney disease and CVD morbidity and mortality, including anemia, hyperphosphatemia, and hyperparathyroidism. Finally, physicians should be careful to avoid therapeutic nihilism in patients with kidney disease; those at highest risk of CVD are likely to receive the greatest benefit from cardiovascular therapies.     

Clinical epidemiology of cardiovascular disease in chronic kidney disease

Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The clinical epidemiology of CVD in CKD is challenging due to a prior lack of standardized definitions of CKD, inconsistent measures of renal function, and possible alternative effects of 'traditional' CVD risk factors in patients with CKD. These challenges add to the complexity of the role of renal impairment as the cause or the consequence of cardiovascular disease. The goal of this review is to summarize the current evidence on: (1) the incidence and prevalence of CVD in chronic renal insufficiency and in ESRD, (2) risk factors for CVD in CKD, (3) the outcomes of patients with renal failure with CVD, and (4) CKD as a risk factor for CVD. The epidemiological associations implicating the huge burden of CVD throughout all stages of CKD highlight the need to better understand and implement adequate screening, and diagnostic and treatment strategies.     

慢性肾脏病合并结核感染诊治进展

慢性肾脏病（Chronic kidney disease ,CKD）和结核病是危及人类健康的慢性疾病,慢性肾脏病患者感染结核的风险增加,与CKD的进展有关,且肺外结核发生率高,临床症状不典型,结核相关筛查实验阳性率低,CKD患者抗结核药物副作用较普通人群高且严重,预后更差,早期诊断及及时治疗对改善预后有重要意义。     

Baseline assessment. Report of a company wide risk factor survey

CVD accounts for the highest rates of morbidity and mortality among the general population. Unhealthy lifestyle practices are largely responsible for this occurrence. Risk factor prevalence of smoking, uncontrolled high blood pressure, and high serum cholesterol levels contribute to the likelihood of developing CVD. Two or more of these risk factors can place individuals at higher risk of developing CVD. Completing a heart health survey of risk factor prevalence among a working population will give occupational health professionals a basis on which to set goals and objectives for effective CVD intervention programs.     

Should eGFR and albuminuria be added to the Framingham risk score? Chronic kidney disease and cardiovascular disease risk prediction

Presence of chronic kidney disease (CKD) defined as decreased glomerular filtration rate (GFR) and/or increased urine albumin excretion is associated with heightened risk of cardiovascular disease (CVD) and all-cause as well as CVD mortality. Although CKD is strongly linked with CVD, it remains undetermined whether this strong association is simply due to shared CVD risk factors or unique traits consequential to CKD. The probability of future CVD events can be estimated with reasonable accuracy using the Framingham equation which was derived from the Framingham study, a community-based cohort of 5,209 white adults aged 30-62 years who were first examined in 1948. Efforts to capture excess CVD risk associated with CKD have been evaluated by adding estimated GFR, cystatin C, serum creatinine and measures of urinary albumin excretion to the Framingham equation which is based on traditional cardiovascular risk factors. Although decreased GFR and increased urine albumin excretion are consistently associated with cardiovascular outcomes, the addition of these factors to the Framingham equation has not been shown to substantially improve overall CVD risk prediction in populations not enriched with CKD. Moreover, the Framingham equation itself underpredicts cardiovascular events among adults with stage 3 and 4 CKD without clinical CVD. Given the poor performance of the Framingham equation in adults with CKD, future studies should explore risk equations which include traditional CVD risk factors and the unique comorbidities associated with CKD for prediction of cardiovascular events in adults with CKD.