Chronic Kidney Disease (CKD) patients show lipid and lipoprotein metabolism disturbances . Phosphatidylinositol and phosphatidic acid are not present in the erythrocyte membranes of CKD patients. Rheological properties of erythrocytes, such as osmotic resistance, deformability and mechanical fragility change in these patients. Many authors associate these disturbances with the lipid composition of the erythrocyte membrane . During hemodialysis total cholesterol content and the cholesterol/phospholipids ratio increase in the cytoplasmic membrane. These are the main factors responsible for the alterations of membrane fluidity that potentially impact on erythrocyte deformability and osmotic resistance .
An abnormal phospholipid metabolism was suggested to play an important role in the progression of atherosclerosis in hemodialysis patients .
A number of observational studies reported an inverse association between CVD and dietary intake or plasma concentrations of omega-3 PUFAs, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), suggesting that supplementation of ω-3 fatty acid might exert protective effects on CVD [15–19]. The protective action of ω-3 fatty acids upon the CV system is mediated by their ability to suppress inflammation and to inhibit platelet activation/adhesion, as well as by a direct effect on the myocardium . This latter effect is related to their capacity to prolong the refractory state of cardiomyocytes via an interaction with fast-acting sodium channels and the L-type calcium channels. These actions are mediated by EPA and DHA in cardiomyocyte membranes. A comparative study revealed a strong correlation between n-3 fatty acids concentration in myocardium and in erythrocytes . ESRD patients on maintenance HD are at risk for inadequate ω-3 intake because they may find foodstuffs less palatable as a result of alterations in taste; moreover, renal dietary recommendations do not encourage fish consumption due to adverse hyperphosphatemia . Therefore, malnutrition is a frequent occurrence in HD patients and may be caused by either inadequate food intake and enhanced intradialytic loss of nutrients, or by hypercatabolism due to ESRD comorbidities or associated to dialysis treatment .
Phospholipids play an essential role in cell membrane structure and function. The length and degree of phospholipids and unsaturated fatty acids are main determinants of cell membrane fluidity, transport systems, activity of membrane-bound enzymes and susceptibility to lipid peroxidation . The serum fatty acid lipid profile (especially phospholipids) reflects the fatty acid composition of cell membranes . In our study, HD patients had reduced plasma EPA, ARA, LA and Dihomo-γ-linolenic acid (DGLA), associated with high plasma triglycerids.
Christensen and Coworkers demonstrated a possible anti-arrhythmic effect of ω-3 PUFAs, as they found a positive correlation between Heart Rate Variability (HRV) and the composition in cell membrane of ω-3 PUFAs in CKD patients . Further intervention studies based on the administration of ω-3 confirmed the ω-3 PUFAs cardio-protective role [27, 28] and showed that the composition of erythrocyte EPA and DHA reflects that of the myocardium and is influenced by diet . We thus investigated erythrocyte membrane EPA and DHA as its “ω 3-index” (EPA + DHA) correlates to human myocardiocyte membrane ω 3-index.
We found a significant reduction of erythrocyte ω-3 fatty acid α-Linoleic Acid in HD patients compared to healthy controls. This reduction may be due to the conversion of ALA into EPA and possibly into DHA. The conversion of ALA into EPA is limited in humans, but may be physiologically and clinically important. Several dietary factors are thought to influence the conversion of ALA into EPA, the kind of protein consumed and the amount of dietary EPA among others . Another possible reason for lower erythrocyte ALA in HD patients is that many foods rich in ALA (such as nuts, seeds and seed oils including flaxseed oil, English walnuts, canola oil, and soybean oil) are not recommended in uremic patients because they are rich in potassium.
Furthermore, HD patients exhibited a significant decrease of erythrocyte membrane LA and ARA that reduces the cardiovascular protective effect exerted by LA, as reported by Laaksonen et al. . Arachidonic acid, a ω-6 fatty acid, is a substrate for the production of various pro-oxidant pro-inflammatory mediators and signal transduction molecules.
In previous investigations a significant increase of erythrocyte membrane fatty acids were reported in Korean ESRD patients . The reason for these discrepant data is unclear. However, differences in dietary composition, genetic factors  and different analytical methods that have been standardized only recently may be advocated.
We finally observed both plasma and erythrocyte ω6/ω3 ratios increased in HD patients compared to healthy controls; in earlier prospective studies the supplementation of ω3 fatty acid reduced membrane ω6/ω3 ratio significantly in these patients and lowered plasma ARA in healthy subjects and in patients with coronary heart disease [33, 34]. The CV protective effect of ω-3 PUFAs may be related to their anti-thrombotic, lipid-lowering and anti-inflammatory actions [35, 36].
The main limitation of our study was a correct evaluation of the real feeding habits of HD patients on “free” diet by means of a self-administered questionnaire. A significant discrepancy is patent when the mean caloric intake reported by patients is compared to their “real” caloric intake derived from BMI calculation (see Table 3, lines 1 to 3). This underestimation of the reported caloric intake may be due to a low adherence of patients to dietary prescriptions and subsequent insincere answers.