Cardiovascular disease (CVD) is the most common cause of death in CKD patients receiving dialysis. Contributing significantly to the high cardiovascular mortality rate are disturbances in lipid metabolism, especially hypertriglyceridemia.
Nevertheless, the mechanism behind the pathophysiologic disorder is incompletely understood. Currently, the most prevalent etiology for CKD is diabetes mellitus, and patients with both disorders are at great risk of death due to CVD. Thus, designing effective interventions directed at lipid metabolism is key to improving mortality rates in this population.
It has been well documented that CKD patients have dyslipoproteinemia. In fact, the qualitative characteristics of dyslipoproteinemia found in the early stages of CKD are the same as those seen in later, more advanced stages.
The abnormalities are more accurately observed in serum apolipoprotein measurements than in lipid profiles. Lee et al reported alterations in lipid metabolism in patients with CKD stage 3 and higher (Kidney Int. 2002;61:209-218). Specific metabolic changes were characterized by increases in plasma total cholesterol; triglycerides; very- low-density lipoprotein cholesterol (VLDL); LDL; and lipoproteins B, C-III, E, and C-III-HP (apoprotein C-III bound to apoprotein B-containing lipoproteins).
This altered lipid metabolism may be the result of many variables, such as insulin resistance, hypertension, diabetes, and obesity. However, teasing out the risk/benefit ratio of obesity and lipid concentrations is difficult in dialysis patients, who are subject to reverse epidemiology.
Current epidemiologic data indicate that low serum cholesterol and low BMI are independent risk factors for death in these patients. Thus, even though CVD is the leading cause of death, the traditional medical model of using pharmacotherapy to reduce cholesterol and triglyceride concentrations to very low levels may not be appropriate in patients with end-stage renal disease.
Alternative treatments, such as the use of omega-3 fatty-acid supplementation, may be warranted as a first-line intervention for dyslipidemia. Omega-3 fatty acids are thought to reduce the incidence of CVD through their ability to suppress inflammation and inhibit platelet activation and by direct action on the myocardium (J Ren Nutr. 2009;19:267-274).
Two specific components of omega-3 fatty acids are thought to be important in CVD prevention: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA exert their mediating effects on the cardiomyocytes through interaction with sodium channels.
Evidence of benefit
Recent studies have demonstrated some significant effects of omega-3 supplementation on cardiovascular parameters in hemodialysis (HD) patients. Bowden et al compared fish oil (omega-3 fatty-acid source containing 160 mg EPA and 100 mg DHA) with corn oil (omega-6 fatty-acid source) supplementation in HD patients over six months (J Ren Nutr. 2009;19:259-266).
The results showed that although LDL levels increased in both groups, the increase in the corn-oil group was greater. Moreover, LDL particle number decreased significantly in the fish-oil group but increased in the corn-oil group. In addition, HDL concentrations rose significantly in the fish-oil group and declined in the corn-oil group. These findings provide promising evidence for the effective use of fish oil to lower the risk of CVD in HD patients.
In a larger randomized clinical trial, Svensson et al. compared omega-3 polyunsaturated fatty-acid supplementation (45% EPA and 37.5% DHA) with a control supplement (olive oil) in 206 HD patients over three months (Nephrol Dial Transplant. 2008;23:2918-2924). According to the data, the omega-3 treatment group had significantly lower serum triglycerides; however, the investigators observed no effect on total cholesterol, HDL, LDL, lipoprotein(a), or apoprotein B concentrations.
Similar to the previous studies, Vernaglione et al compared omega-3 supplementation (2 g/day) with olive oil (2 g/day) for four consecutive months in 24 HD patients (J Nephrol. 2008;21:99-105). At the end of the study period, systolic, diastolic, and mean BP were significantly lower with the omega-3 intervention. However, there were no differences in lipid concentrations.
Although the results of these studies are inconsistent, they do indicate that the inexpensive and relatively safe intervention of using omega-3 fatty acids may be effective in lowering the risk of CVD in HD patients. The mechanism appears to involve modulation of such risk factors as LDL particles, triglycerides, and BP while increasing HDL, a protective factor in HD patients.
Dr. Steiber is Coordinator of the Dietetic Internship/Master’s Degree Program at Case Western Reserve University in Cleveland.