Koulouridis E, Tzilianos M, Katsarou A, Costimba I, Klonou E, Panagiotaki E, Georgalidis C, Krokida A, Delaportas N, Lachanas A, Karaliotas G, Kaliolia I
Nephrology Department, General Hospital of Corfu, Greece.
Int Urol Nephrol. 2001;33(2):207-15. doi: 10.1023/a:1015254315839.
Mild to moderate hyperhomocysteinemia is very common among patients undergoing haemodialysis. There is sufficient evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular and or atheromatous disease in end stage renal failure patients. Vitamin supplementation such as vitamin B6, B12 or folate has been proposed to correct this metabolic disturbance and it is to be proved if this intervention benefit these patients, but there is no agreement whether oral folate supplementation is capable to normalize homocysteine levels in end stage renal failure patients.
In 53 patients, undergoing haemodialysis, homocysteine levels (Hcy), folate, vitamin B12, ferritin and C-reactive protein (CRP) were estimated before and after dialysis, without folate supplementation. Thirty voluntary blood donors were used as controls to compare homocysteine levels. After four weeks of oral folate supplementation (10 mg/24 hours) the levels of homocysteine, serum folate and intra-erythrocyte folate were estimated again. Eighteen months later the survival rate of our patients was recorded and analyzed in relation to Hcy and CRP levels.
The results showed that haemodialysis patients exhibited, almost, fourfold higher homocysteine levels than controls (27.39 +/- 11.54 vs 7.38 +/- 3.5, t = -8.2, p = 0.000000). Folate levels, vitamin B12 and CRP increase significantly after haemodialysis where as homocysteine levels decrease (Hcy1 vs. Hcy2: z = 2.08, p = 0.03). Fourteen (14) patients suffered from coronary heart disease (CHD) and they exhibited the higher levels of homocysteine (Hcy1 vs. CHD: z = -3.4, p = 0.0006). All estimations performed revealed a negative correlation between homocysteine levels and plasma or intra-erythrocyte folate. No other variable exhibited any significant influence upon homocysteine levels. After folate supplementation homocysteine levels in the whole number of patients were unchanged (Hcy(before) vs. Hcy(after): 27.39 +/- 11.54 vs. 26.95 +/- 8.22, z = 0.3, p = 0.7, NS). When patients with homocysteine levels higher than 24 micromol/L were selected, a significant decrease was observed (34.77 +/- 9.32 vs. 30.0 +/- 8.05, z = 2.09, p = 0.02). Forty-two patients were treated with erythropoietin for their anemia and we found a positive correlation between C-reactive protein levels and rhu-Epo dose (CRP vs. Epo: r = 0.45, p = 0.002). Homocysteine levels did not exhibit any significant influence upon short-term survival (U = -0.37, p = 0.3, NS) where as CRP levels exhibit a significant influence upon short-term survival (U = 2.15, p = 0.005).
Homocysteine levels in haemodialysis patients are fourfold higher than healthy controls. Folate, vitamin B12 and CRP increases significantly after dialysis. Patients with coronary heart disease exhibit the highest levels of homocysteine. The homocysteine levels are inversely related with the folate levels. The exogenous folate supplementation increase the serum folate levels but decreases homocysteine only in patients with higher than mild hyperhomocysteinemia. Hcy doesn't exert any significant effect upon the short-term survival of the haemodialysis patients but CRP level is a god predictor of the short-term survival of these patients.
轻至中度高同型半胱氨酸血症在接受血液透析的患者中非常常见。有充分证据表明，高同型半胱氨酸血症是终末期肾衰竭患者发生心血管疾病和/或动脉粥样硬化疾病的独立危险因素。有人提出补充维生素，如维生素B6、B12或叶酸来纠正这种代谢紊乱，这种干预是否对这些患者有益还有待证实，但对于口服叶酸补充剂能否使终末期肾衰竭患者的同型半胱氨酸水平正常化，目前尚无定论。
对53例接受血液透析的患者在未补充叶酸的情况下，分别于透析前后测定同型半胱氨酸水平（Hcy）、叶酸、维生素B12、铁蛋白和C反应蛋白（CRP）。选取30名自愿献血者作为对照，比较同型半胱氨酸水平。在口服叶酸补充剂（10mg/24小时）四周后，再次测定同型半胱氨酸、血清叶酸和红细胞内叶酸水平。18个月后，记录并分析患者的生存率与Hcy和CRP水平的关系。
结果显示，血液透析患者的同型半胱氨酸水平几乎是对照组的四倍（27.39±11.54 vs 7.38±3.5，t=-8.2，p=0.000000）。血液透析后叶酸水平、维生素B12和CRP显著升高，而同型半胱氨酸水平降低（Hcy1 vs. Hcy2：z=2.08，p=0.03）。14名患者患有冠心病（CHD），他们的同型半胱氨酸水平较高（Hcy1 vs. CHD：z=-3.4，p=0.0006）。所有测定结果均显示同型半胱氨酸水平与血浆或红细胞内叶酸呈负相关。没有其他变量对同型半胱氨酸水平有任何显著影响。补充叶酸后，所有患者的同型半胱氨酸水平未发生变化（Hcy（治疗前）vs. Hcy（治疗后）：27.39±11.54 vs. 26.95±8.22，z=0.3，p=0.7，无显著性差异）。当选择同型半胱氨酸水平高于24μmol/L的患者时，观察到同型半胱氨酸水平显著下降（34.77±9.32 vs. 30.0±8.05，z=2.09，p=0.02）。42名患者因贫血接受促红细胞生成素治疗，我们发现C反应蛋白水平与重组促红细胞生成素剂量呈正相关（CRP vs. Epo：r=0.45，p=0.002）。同型半胱氨酸水平对短期生存没有显著影响（U=-0.37，p=0.3，无显著性差异），而CRP水平对短期生存有显著影响（U=2.15，p=0.005）。
血液透析患者的同型半胱氨酸水平比健康对照组高四倍。透析后叶酸、维生素B12和CRP显著升高。冠心病患者的同型半胱氨酸水平最高。同型半胱氨酸水平与叶酸水平呈负相关。外源性叶酸补充剂可提高血清叶酸水平，但仅在高于轻度高同型半胱氨酸血症的患者中降低同型半胱氨酸水平。Hcy对血液透析患者的短期生存没有显著影响，但CRP水平是这些患者短期生存的良好预测指标。
