Kaysen George A, Eiserich Jason P
Division of Nephrology, Department of Medicine University of California Davis, Davis, CA 95616, USA.
J Am Soc Nephrol. 2004 Mar;15(3):538-48. doi: 10.1097/01.asn.0000111744.00916.e6.
Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.
心血管疾病在慢性肾脏病（CKD）患者中很常见。随着肾功能衰竭，许多患者会逐渐营养不良，白蛋白、前白蛋白和转铁蛋白水平降低就是证明。营养不良的患者C反应蛋白（CRP）、白细胞介素-6（IL-6）水平升高，到终末期时还会伴有心血管疾病。许多导致CKD的疾病，如糖尿病和高血压，也与心血管疾病有关。因此，在CKD早期，肾衰竭本身直接导致炎症-营养不良-动脉粥样硬化模式的直接作用尚未完全确立。然而，进行性肾衰竭的某些方面会导致血浆成分以及内皮结构和功能的变化，从而有利于血管损伤。随着肾功能衰竭，肝脏载脂蛋白A-I合成减少，高密度脂蛋白（HDL）水平下降。HDL是一种重要的抗氧化剂，可保护内皮免受细胞因子的影响。炎症会导致HDL出现进一步的结构和功能异常。载脂蛋白C III（apo C III）是脂蛋白脂肪酶的竞争性抑制剂，在CKD中会升高。由于包含极低密度脂蛋白（VLDL）和乳糜微粒残粒的中间密度脂蛋白（IDL）积累，血清甘油三酯水平升高。这些会阻碍血管舒张，并与心血管疾病有关。肾素-血管紧张素轴的激活是许多肾脏疾病以及对肾实质丧失的适应性反应的一个组成部分。血管紧张素II（AngII）激活NADPH氧化酶，导致超氧阴离子生成，一氧化氮（NO）可用性降低，进一步损害血管功能。超氧化物歧化产生的过氧化氢（H₂O₂）会刺激血管细胞增殖和肥大。白细胞衍生的髓过氧化物酶在炎症血管系统中起“NO氧化酶”的作用，导致NO生物利用度降低和血管反应性受损。脂蛋白组成和结构的变化以及AngII介导的内皮功能改变会放大后续炎症事件的影响。
