肾性贫血患者血红蛋白波动与预后关系

慢性肾脏病(CKD)患者血红蛋白波动性大于正常人。CKD患者的血红蛋白高波动性是否与死亡预后直接有关?针对这个问题，当前已经发表了大量基于观察性数据的分析结果，但结果互相矛盾。本文对已经发表的数个有代表性的观察性研究进行深入的剖析，提出血红蛋白波动与患者预后关系的独到见解。     

Hypertension,left ventricular hypertrophy and chronic kidney disease

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH.     

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??Abstract??Protein-energy malnutrition (PEM) is a common complication in peritoneal dialysis patients.The morbidity increases with the extension of the duration of dialysis.PEM seriously affect patients?? quality of life??hospitalization rate and mortality.The main factors leading to PEM are inflammation??diabetes??high peritoneal transporter and elder age of patients.The main countermeasures to prevent PEM in PD patients include nutritional support??use of amino acid peritoneal dialysis solution??improvement of micro-inflammatory state??adequate dialysis??better fluid volume control??correction of metabolic acidosis??and the protection of residual renal function.In addition??automated peritoneal dialysis (APD) has the advantage of delivering higher doses of dialysis??more exchanges??shorter dwelling time??and thus might be more effective in management of PEM in PD patients.     

Inflammatory and atherosclerotic interactions in the depleted uremic patient

Despite the improvements in dialysis technology, the cardiovascular mortality rate is still unacceptably high among dialysis patients. It is obvious that traditional risk factors, such as hypertension, chronic heart failure (CHF), dyslipidemia and diabetes mellitus, may account for a large part of the increased cardiovascular mortality rate in these patients. However, based on recent research it could be speculated that other, non-traditional risk factors might also contribute to the high cardiovascular mortality rate in dialysis patients. Chronic inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature in dialysis patients and is associated with an increased cardiovascular morbidity and mortality. Indeed, elevated levels of pro-inflammatory cytokines (such as TNF-alpha, IL-1 and IL-6) may cause malnutrition and progressive atherosclerotic cardiovascular disease by several pathogenetic mechanisms, which will be discussed in this review. Based on the strong associations observed between malnutrition, inflammation and atherosclerosis in patients with chronic renal failure (CRF) we have proposed that these features constitute a specific syndrome (MIA), which carries a high mortality rate. As elevated levels of pro-inflammatory cytokines may play a central part in the vicious circle of malnutrition, inflammation and atherosclerosis, further research is needed to investigate whether or not different anti-cytokine treatment strategies may improve survival in dialysis patients.     

Dyslipidemia in Chronic Kidney Disease: Are Statins Still Indicated in Reduction Cardiovascular Risk in Patients on Dialysis Treatment?

Background: Chronic kidney disease (CKD) is an increasingly health disease all around the world with a high burden of mortality and cardiovascular (CV) morbidity rate. Even when renal replacement therapy is reached, more than half patients die, mainly for CV causes due either to uremia‐related cardiovascular risk factors (such as anemia, hyperhomocysteinemia, mineral bone disease–CKD with hyperparathyroidism, oxidative stress, hypoalbuminemia, chronic inflammation, prothrombotic factors) or to traditional ones (age, male gender, diabetes, obesity, hypertension, smoking, insulin levels, family history, dyslipidemia). Among the latter causes dyslipidemia represents one of the major, potentially correctable risk factor. Methods and Results: Statins have demonstrated to effectively and safely reduce cholesterol levels in CKD patients. Here we will examine the effects of statins on CV risk factors in CKD patients and particularly in patients on dialysis treatment, in the light of the unfavorable results of the large trials 4D and AURORA, recently published, underlining the role of malnutrition/inflammation as confounding factor. Probably it will be that only with a real prevention, starting statins even in the early stages of CKD, as indicated by post hoc analysis of large trials, that we will reach results in reducing the mortality rate in CKD patients. In the meanwhile, all the other remediable CV risk factors have to be at the same time corrected.     

慢性肾功能不全与心血管疾病的关系

心血管疾病是造成终末期肾脏病患者死亡的主要原因,除了一般人群常见的心血管疾病危险因素(如高血压、糖尿病、高脂血症、吸烟、家族史、年龄、性别)外,目前认为慢性肾脏疾病相关危险因素如贫血、高同型半胱氨酸血症、高磷血症、低蛋白血症、微炎症状态、氧化应激等与终末期肾脏疾病患者心血管疾病的发生有关。     

C-reactive protein in end-stage renal disease: are there reasons to measure it?

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this population, inflammation (a common phenomenon in ESRD), and other non-traditional risk factors are likely to contribute. Among several inflammatory biomarkers used to assess inflammation, high-sensitivity C-reactive protein (hs-CRP) has attracted the most interest. Indeed, in the general population the consistency of prognostic data for hs-CRP and the practicality of its use have led to suggestions that CRP should be used as a clinical criterion for global cardiovascular risk prediction. As CRP is so strongly associated with vascular disease, it has been suggested that this protein is not only a marker, but also a mediator, of atherogenesis. Indeed, recent in vitro data from studies on endothelial cells, monocytes-macrophages and smooth muscle cells support a direct role for CRP in atherogenesis. In ESRD, hs-CRP has been proven to be a strong predictor of both cardiovascular and all-cause mortality, and associated with oxidative stress, vascular calcification and endothelial dysfunction. As recent studies suggest that interleukin-6 may be a somewhat better outcome predictor than hs-CRP, comparative studies are needed to evaluate which inflammation biomarker is the most cost-effective predictor of outcome in the ESRD patient population.     

Mechanisms Linking Nonalcoholic Fatty Liver Disease with Coronary Artery Disease

The most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is coronary artery disease (CAD), not chronic liver disease. Fatty liver increases cardiovascular risk by classical (dyslipidemia, hypertension, diabetes) and by less conventional mechanisms. Common pathways involved in the pathogenesis of fatty liver and CAD includes hepatic insulin resistance and sub clinical inflammation. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased FFA, which causes lipotoxicity and impairs endothelium-dependent vasodilatation, increases oxidative stress, and has a cardio toxic effect. Additional metabolic risk factors include leptin, adiponectin, pro inflammatory cytokines [such as IL-6, C-reactive protein and plasminogen activator inhibitor-1 (PAI-1)], which together lead to increased oxidative stress and endothelial dysfunction, finally promoting coronary artery disease (CAD). When classical risk factors are superimposed on fatty liver accumulation, they may further increase the new metabolic risk factors, exacerbating CAD. The clinical implication is that patients with NAFLD are at higher risk (steatohepatitis, diabetes, obesity, atherogenic dyslipidemia) and should undergo periodic cardiovascular risk assessment including the Framingham score, cardiac effort test, and measurement of intimae-media thickening of the carotids arteries. This may improve risk stratification for CAD.     

Can the progression of chronic renal failure be delayed?

Chronic renal failure does not only involve the risk for the patient of becoming dependent on hemodialysis, but also increases the risk of premature death due to cardiovascular events. In most renal diseases, progressive chronic loss of renal function develops once a critical extent of renal damage has occurred, independent of the course of the underlying renal disease. The key factors driving the progressive loss of renal function are, apart from the underlying nephrological disease, arterial hypertension and diabetes mellitus. The loss of renal function is also promoted by other factors, such as increased intake of dietary proteins, chronic inflammation, smoking, and anemia. With the help of a multimodal therapeutic concept, the progression of chronic renal failure can be delayed effectively. This approach comprises strict blood pressure control with a target blood pressure of 130/80 mmHg in patients with micro-albuminuria and of 120/75 mmHg in patients with proteinuria of >1 g/d. The preferred drugs for the treatment of hypertension are ACE inhibitors and angiotensin receptor blockers. In diabetics with renal insufficiency, target HbA1c levels below 7% are to be aimed for. Dietary protein intake should be restricted to 0.8-1 g/kg body weight/d. Additional therapeutic targets include nicotine abstinence, early treatment of renal anemia, weight reduction, and, if indicated, lipid-lowering therapy.     

Premature cardiovascular disease in chronic renal failure (CRF): A model for an advanced ageing process

Ageing leads to a decline in renal function that becomes obvious in individuals with hypertension, vascular disease, or diabetes mellitus. In the absence of such precipitating factors old age induces a reduction of renal functional reserve. It is well known that even modest declines in renal excretory function enhance the cardiovascular risk of the patient by means of myocardial remodelling, arteriosclerosis and atherosclerosis. An important non-traditional risk factor for vascular disease is chronic inflammation. Patients with renal dysfunction tend to have systemic inflammatory activation even in the absence of infection. Subclinical inflammation might be related to cellular senescence mechanisms in leukocytes that are fostered by renal insufficiency. This effect as well as enhanced oxidative stress resemble typical characteristics of both advanced ageing and renal failure. Facing these similarities, chronic renal failure might be a model that allows investigation of accelerated ageing in the vascular system.