Bayés Beatriu, Pastor M Cruz, Bonal Jordi, Juncà Jordi, Hernandez José M, Riutort Nadal, Foraster Andreu, Romero Ramón
Nephrology Department, University Hospital Germans Trias i Pujol, Badalona, Universidad Autonoma de Barcelona, Barcelona, Spain.
Nephrol Dial Transplant. 2003 Jan;18(1):106-12. doi: 10.1093/ndt/18.1.106.
Cardiovascular disease (CVD) is common in haemodialysis patients with chronic renal insufficiency and is the leading cause of death. The accelerated state of atherosclerosis found in these patients is due to a combination of different mechanisms. Recent studies confirm that inflammation plays an important role in the development of atherosclerosis. However, the role of hyperhomocysteinaemia and the immune response to oxidation of low-density lipoproteins (LDL) remains unclear and studies show contradictory results. The objective of this study was to determine whether there is a relationship between inflammation, hyperhomocysteinaemia and oxidative stress and whether these CVD risk factors are predictors of mortality in haemodialysis patients.
A prospective follow-up study was carried out in 94 stable, chronic haemodialysis patients for 24 months (July 1999-July 2001). All the patients were given folic acid and vitamin B complex supplements. Homocysteine was determined by fluorescence polarization immunoassay. C-reactive protein (CRP) levels were determined by chemiluminescent enzyme-labelled immunometric assay. Plasma copper oxidized anti-LDL (oxLDL) antibodies were measured by ELISA using native LDL and oxLDL as antigens.
Thirty-two patients died during the study and 59.3% of the deaths could be attributed to CVD (eight to acute myocardial infarction and 11 to non-coronary vascular disease). The patients had slight hyperhomocysteinaemia (25.8 +/- 7.82 micromol/l), evidence of inflammation (CRP 5.16 mg/l (0.35-88.7)) and oxidative stress (oxLDL antibodies = 162 +/- 77 optical density at 495 nm x 1000). Age (P < 0.01), CRP (P = 0.03) and the oxLDL antibody titre (P < 0.01) were predictive of mortality. The patients who died from heart disease showed higher oxLDL antibody titres (P = 0.03). No correlation was found between homocysteine, CRP and the oxLDL antibody titre, or between serum homocysteine levels and the different causes of mortality.
These results suggest that lipid peroxidation and inflammation, but not hyperhomocysteinaemia, are the main risk factors for mortality in haemodialysis patients receiving vitamin supplements. As the study was carried out in a relatively limited number of patients, our findings need to be confirmed in a larger patient population.
心血管疾病（CVD）在慢性肾功能不全的血液透析患者中很常见，是主要死因。这些患者中发现的动脉粥样硬化加速状态是多种不同机制共同作用的结果。近期研究证实炎症在动脉粥样硬化发展中起重要作用。然而，高同型半胱氨酸血症以及对低密度脂蛋白（LDL）氧化的免疫反应的作用仍不明确，研究结果相互矛盾。本研究的目的是确定炎症、高同型半胱氨酸血症与氧化应激之间是否存在关联，以及这些心血管疾病风险因素是否为血液透析患者死亡率的预测指标。
对94例稳定的慢性血液透析患者进行了为期24个月（1999年7月至2001年7月）的前瞻性随访研究。所有患者均补充叶酸和复合维生素B。采用荧光偏振免疫分析法测定同型半胱氨酸。采用化学发光酶标记免疫分析法测定C反应蛋白（CRP）水平。以天然LDL和氧化LDL为抗原，采用ELISA法测定血浆铜氧化抗LDL（oxLDL）抗体。
研究期间32例患者死亡，59.3%的死亡可归因于心血管疾病（8例死于急性心肌梗死，11例死于非冠状动脉血管疾病）。患者存在轻度高同型半胱氨酸血症（25.8±7.82μmol/L）、炎症证据（CRP为5.16mg/L（0.35 - 88.7））和氧化应激（oxLDL抗体 = 162±77光密度值（495nm×1000））。年龄（P < 0.01）、CRP（P = 0.03）和oxLDL抗体滴度（P < 0.01）可预测死亡率。死于心脏病的患者oxLDL抗体滴度更高（P = 0.03）。未发现同型半胱氨酸、CRP与oxLDL抗体滴度之间存在相关性，血清同型半胱氨酸水平与不同死亡原因之间也无相关性。
这些结果表明，脂质过氧化和炎症而非高同型半胱氨酸血症是接受维生素补充的血液透析患者死亡的主要风险因素。由于本研究纳入的患者数量相对有限我们的研究结果需要在更大规模的患者群体中得到证实。
