Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients

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.