Plasma Fatty Acid Composition in Continuous Ambulatory Peritoneal Dialysis Patients: An Increased Omega-6/Omega-3 Ratio and Deficiency of Essential Fatty Acids

Abstract

Patients with end-stage renal disease, including those treated with peritoneal dialysis, have a high risk for death, particularly from cardiovascular causes. Plasma fatty acid (FA) composition is used as an indicator of disease risk, because its alteration has been related to metabolic disease and cardiovascular disease. For this purpose, we have measured plasma FA composition in continuous ambulatory peritoneal dialysis (CAPD) patients and compared them with those of healthy subjects. This study was performed on 51 (21 M, 30 F) CAPD patients at least 6 months under dialysis, aged 20–75 years (mean 47.81 ± 11.8 years) and 45 (25 M, 20 F) healthy control subjects aged 20–60 years (mean 38.62 ± 12.9 years). Plasma 10-cis-pentadecanoic acid, 10-cis-heptadecanoic acid, heneicosanoic acid, tricosanoic acid, nervonic acid, saturated fatty acid, and monounsaturated FA levels and delta 9 desaturase activity were significantly higher whereas linoleic acid, linolenic acid, 11,14-eicosedienoic acid, arachidonic acid, docosahexaenoic acid, and omega-3 FA levels were significantly lower in the CAPD group than those in the healthy group. Our results show that there are FA abnormalities and especially a depletion in essential FA levels and a high level of omega-6/omega-3 ratio in CAPD patients, the underlying mechanism of which is not known and needs to be investigated. Therefore, we believe that essential FA supplementation should be encouraged for CAPD patients.     

Plasma and Erythrocyte Phospholipid Fatty Acids Composition in Serbian Hemodialyzed Patients

Dyslipidemia is one of the possible risk factors for advanced atherosclerosis in patients with chronic renal failure. Abnormal phospholipid metabolism may play an important role in the progression of atherosclerosis in patients with renal failure. The aim of this study was to determine specific characteristics of plasma and erythrocyte phospholipid content and fatty acid composition in 37 patients with chronic renal failure on hemodialysis (HD). The results were compared with the characteristics of healthy subjects. Briefly, plasma triglyceride (p < 0.001), total cholesterol (p < 0.05), and total phospholipids (p < 0.01) levels were significantly higher and HDL-cholesterol level significantly lower (p < 0.01) in HD patients. Plasma phosphatidylcholine and phosphatidylethanolamine concentration were significantly higher (p < 0.001) in HD patients. The plasma phospholipid fatty acids composition indicated significantly (p < 0.01) higher level of oleic (18:1 n-9) and lower levels of eicopentaenoic (20:5 n-3 EPA) and docosahexaenoic (22:6 n-3 DHA) acids (p < 0.05). However, in HD patients, the relative concentration of plasma phospholipid n-6 polyunsaturated fatty acid (PUFA) was significantly lower (p < 0.05). The fatty acid composition of erythrocyte phospholipid in HD patients was modified with EPA and DHA levels significantly lowered (p < 0.05). Our results demonstrate an abnormal phospholipid metabolism and deficiency of n‐3 PUFA in plasma and erythrocyte phospholipids in hemodialyzed patients.     

Effect of Hemodialysis on the Content of Fatty Acids in Monolayers of Erythrocyte Membranes in Patients with Chronic Renal Failure

Lipid metabolism disorders are found in patients with chronic renal failure (CRF). Changes in the content of fatty acids of the phospholipid fraction of erythrocyte membranes can lead to changes in the rheological properties. The objective of our study was to assess the effect of hemodialysis on the composition of fatty acids in two fractions of phospholipids: sphingomyelin (SPH, representative of the external monolayer) and phosphatidylethanolamine (PE, representative of the internal monolayer). Venous blood was drawn from patient with CRF before and after the HD procedure. Lipids from the erythrocyte stroma were extracted using the Rose and Oklander method and then were separated into phospholipid fractions using thin-layer chromatography (TLC). PE and SPH fractions were extracted, and the fatty acid profile was determined using gas chromatography (Perkin Elmer 8400; RTx 2330 column; length: 105 m). In the phospholipid fractions tested, a high content of saturated FA with a medium carbon chain (C 16:0 to C 18:2) and a long carbon chain such as C 24:0, C 24:1; C 22:6; and C 26:0 was found. The HD procedure affected the FA profile in the fractions tested. The proportion of saturated and unsaturated long-chain FA (above 18 C) increased in PE. However, the content of medium-chain FA C 16:0 to C 18:1 decreased. A significant decrease in the content of the majority of long-chain FA could be noted in SPH. The ratio of unsaturated (U) to saturated (S) fatty acids in the SPH fraction increased. Hemodialysis has a significant effect on the content of fatty acids in the PE and SPH fractions of erythrocyte membranes in patients with CRF.     

Effects of Low Molecular Weight Heparin on the Frequencies of Intradialytic Arrhythmias in Hemodialysis Patients

Arrhythmia is known to cause sudden death in hemodialysis patients. Heparin administration releases lipoprotein lipase from the capillary endothelial cell surface, resulting in an increase in the plasma levels of free fatty acids; higher levels of free fatty acids may affect the occurrence of arrhythmias. This study assessed whether the occurrence of arrhythmias during hemodialysis could be suppressed by replacing unfractionated heparin with low molecular weight heparin. Ten dialysis patients who had supraventricular premature contraction and/or ventricular premature contraction were monitored by the Holter electrocardiograph system during hemodialysis. To investigate the effect of each form of heparin on plasma lipid metabolism, the lipoprotein lipase and lipid levels before and during hemodialysis were measured. The occurrence of arrhythmias was significantly suppressed in hemodialysis using low molecular weight heparin, as compared with hemodialysis using unfractionated heparin. Lower lipoprotein lipase and free fatty acids levels were also observed in hemodialysis using low molecular weight heparin. The authors concluded that hemodialysis using low molecular weight heparin instead of unfractionated heparin could be effective in protecting hemodialysis patients with arrhythmias against arrhythmia-related cardiac events.     

糖尿病肾病患者D-二聚体和脂蛋白(a)的变化及其相关性研究

目的:观察血浆D-二聚体(D-dimer,DD)和血清脂蛋白(a)[Lp(a)]在糖尿病肾病(DN)中的变化并 探讨两者之间的关系。方法:根据尿白蛋白排泄率(UAER)将126例2型糖尿病(DM)患者分为单纯糖尿病组(SDM 组)、早期糖尿病肾病组(EDN组)和临床糖尿病肾病组(CDN组),45名健康者作为对照组,分别测定各组血浆DD和 血清Lp(a)的水平。结果:DD、Lp(a)水平SDM组与对照组比较无统计学差异(P>0.05),但EDN和CDN组显著高 于SDM组和对照组(P<0.01),CDN组显著高于EDN组(P<0.01)。DD和Lp(a)分别与UAER呈显著正相关(r= 0.523,0.426,P<0.01)。结论:DN患者血浆DD和血清Lp(a)水平随着UAER的增加而升高,两者之间关系密切,可 能与DN的进展有关。     

Lipoprotein (a) in patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis

Lipoprotein (a) concentrations and apoprotein (a) isoforms weremeasured in 99 haemodialysis and 79 peritoneal dialysis patientsand compared with a normal population. Peritoneal dialysis patientsdemonstrated a threefold and haemodialysis a twofold increasein median Lp(a) values compared to controls (P0.001). The peritonealdialysis group had significantly more patients with Lp(a) valuesgreater than 30 mg/dl compared to controls, (53% versus 22%P0.001). In addition both patient groups demonstrated significanthypertriglyceridaemia (P0.001), reduction in HDL (P0.001) andelevation of the cholesterol/HDL ratio (P0.001) compared withcontrols. Peritoneal dialysis patients also demonstrated significanthypercholesterolaemia (P0.003). Lipoprotein (a) concentrations are considerably elevated inpatients on maintenance dialysis and this occurs in additionto the typical lipoprotein disturbances. This elevation mayincrease vascular risk, particularly in the peritoneal dialysisgroup who also have hypercholesterolaemia and reduced HDL.     

Lipids and lipoprotein(a) as risk factors for vascular disease in patients on renal replacement therapy

A large cohort of patients on renal replacement therapy werescreened for the presence of symptomatic arterial disease affectingthe coronary, cerebral or peripheral circulations. Ninety-twoof 325 patients were found to have vascular disease. Those withvascular disease had significantly higher median lipoprotein(a)[Lp(a)] levels than those without (38.4 vs 14.2 mg/dl, P<0.001),with a preponderance of Lp(a) levels greater than 30 mg/dl (58%vs 25% P<0.001). Apolipoprotein(a) [apo(a)] isoform distributionwas similar between the groups, but those with vascular diseasehad higher Lp(a) levels in the S2, S3/S4 and S4 isoform types.Comparison of 76 matched pairs of patients confirmed elevatedLp(a) levels in those with vascular disease. These patientsalso had significantly higher total cholesterol (6.66 vs 6.02mmol/l) and low-density lipoprotein cholesterol (4.49 vs 3.86mmol/l). Only Lp(a) was independently associated with vasculardisease (P=0.02). Elevated Lp(a) levels are significantly associatedwith the presence of vascular disease in patients on renal replacementtherapy and may constitute another risk factor for the developmentof such disease in these patients.     

Impact of Supplementing Preoperative Intravenous Omega 3 Fatty Acids in Fish Oil on Immunomodulation in Elderly Patients Undergoing Hip Surgery

The aim of this study was to evaluate the immunomodulatory effects of supplementing intravenous omega-3 fatty acids in fish oil (IVFO) in elderly patients undergoing hip surgery. This was a single centre, randomized, controlled, comparative, phase IV study in elderly patients undergoing hip surgery. The subjects, within the age range of 50–90 years, were assigned randomly to the group receiving intravenous omega-3 fatty acids in fish oil (IVFO, Omegaven®) or the control group not receiving intravenous fish oil (n = 20 in each group). IL-6, IL-8, IL-10, and HS-CRP levels were the inflammatory markers assessed in this study. The within-group comparison was done by paired t-test and between-group comparison by unpaired t-test. At day 4, IL-6 values in the IVFO group decreased as compared to day 0. At day 4, IL-8 mean values increased for both IVFO and control groups. This increase was highly significant in the control group (P = 0.0182). IL 10 values decreased at day 4 and increased at day 8 in the IVFO group. Increase in HS-CRP levels was nonsignificant at day 4 in the IVFO group (P = 0.60) and significant at day 8 for the control group (P = 0.0084) as compared to day 0. Various biochemical parameters including albumin, protein, SGOT, SGPT, blood glucose, and urea values generated evidence regarding the safety profile of IVFO. This study suggests a role for IVFO in the short-term suppression of inflammatory mediators for patients undergoing hip surgery. However, further, larger trials may be needed to establish its definitive role in this patient population.     

Relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function.

BACKGROUND: Plasma lipoprotein (a) [Lp(a)] has been shown to be a risk factor for atherosclerosis in numerous studies. However, the catabolism of this lipoprotein is not very clear. We and others have shown that Lp(a) is excreted into urine in the form of fragments. Lp(a) has also been shown to exist in a low-density non-lipoprotein (LDL)-bound form. Since Lp(a) is increased in all forms of kidney disease with reduced excretory kidney function and decreased excretion of apo(a) fragments could be partially responsible for this increase, we investigated the relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function. METHODS: Plasma Lp(a), non-LDL-bound apo(a) and urinary apo(a) fragments were measured in 55 kidney disease patients (28 males and 27 females) and matched controls. RESULTS: Plasma Lp(a) and non-LDL-bound apo(a) were increased in patients, whereas urinary apo(a) was decreased, especially in patients with a creatinine clearance < 70 ml/min. There was a significant correlation between plasma Lp(a) and non-LDL-bound apo(a) in patients and controls. CONCLUSION: We conclude that decreased urinary apo(a) excretion could be one possible mechanism of increased plasma Lp(a) and non-LDL-bound apo(a) in patients with decreased kidney function.     

Lipoprotein (a) levels in those with high molecular weight apo (a) isoforms may remain low in a significant proportion of patients with end-stage renal disease.

BACKGROUND: Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. METHODS: A total of 239 patients at end-stage renal failure (ESRF) were studied prior to the initiation of dialysis. Blood was taken for Lp (a) levels and apo (a) isoforms. Clinical vascular disease (CVD) was assessed on the basis of clinical history and Rose questionnaire. The control group for Lp (a) levels consisted of 228 healthy volunteers. RESULTS: Despite a higher median Lp (a) level in those with HMW isoforms, 30% of patients had Lp (a) levels <10 mg/dl. Overall, 49% patients were identified as having CVD. Diabetes, smoking history and Lp (a) levels were significantly associated with CVD in logistic regression analysis, although when patients with low molecular weight (LMW) and HMW isoforms were analysed separately, Lp (a) levels were not significantly associated with CVD in those with LMW isoforms. The rates of CVD in those with HMW isoform and low Lp (a) levels were significantly lower than those with HMW isoforms and elevated Lp (a) levels, 34 vs 57% (P < 0.01). CONCLUSIONS: Although median Lp (a) levels in those patients at ESRF with HMW isoforms are higher than controls, in a third of such patients Lp (a) levels remain relatively low. These patients have lower rates of CVD than those with high levels of Lp (a).     

Reversal of severe parenteral nutrition-associated liver disease in an infant with short bowel syndrome using parenteral fish oil (Omega-3 fatty acids)

Total parenteral nutrition is an important adjunct in the care of neonates with surgical disorders. Cholestasis is at present the most worrisome complication of this technique; it is difficult to treat and may progress to eventual cirrhosis and liver failure. This article reviews the pertinent clinical and nutritional data in a surgical patient with short bowel syndrome who developed parenteral nutrition-associated liver disease successfully treated with fish-oil based lipids.     

Comparison of 4 % Icodextrin and Omega 3 Fatty Acids in Prevention of Peritoneal Adhesions

Postoperative peritoneal adhesions are major concerns in abdominal surgery. In this experimental study, the effects of 4 % icodextrin and omega-3 fatty acids (ω-3 FA) on prevention of postoperative peritoneal adhesions were evaluated. Twenty-four Wistar albino rats were divided into three groups. After laparotomy, serosal abrasion was carried out by cecal brushing. Intraperitoneally 3 cm³ 0.9 % NaCl, 3 cm³ 4 % icodextrin, and 200 mg/kg ω-3 FAs for each group were applied, and then the abdomen was closed. All subjects sacrificed 10 days postoperatively. Macroscopic and histopathological cellular reactions as a function of giant cell, lymphocyte/plasmocyte, neutrophil, histiocyte, intracellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) were assessed and hydroxyproline levels were measured in all three groups and compared using Kruskal–Wallis and ANOVA tests when appropriate. Macroscopically, both ω-3 FAs and 4 % icodextrin reduced adhesion formation but the difference was not statistically significant (P = 0.253). Histopathological examination revealed that there was no statistical significance in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM-1, and PECAM-1 scores; however, both ω-3 FAs and 4 % icodextrin were found to be prone to reduce fibrosis (P = 0.047), whereas in the ω-3 FA group, histiocytic reaction was significantly increased (P = 0.001), and hydroxyproline levels were significantly lower than other groups (P = 0.044). In this study, ω-3 FAs were found to be superior to 4 % icodextrin with the lower hydroxyproline level and greater histiocytic reaction. Considering these results, ω-3 FAs can be a promising agent in the prevention of adhesion formation.     

Low–Density Lipoprotein Apheresis in the Treatment of Two Patients with Coronary Heart Disease and Extremely Elevated Lipoprotein (a) Levels

Abstract: Hyperlipidemia and elevated lipoprotein (a) (Lp[a]) levels have been linked to the development and progression of premature atherosclerosis. Our study concerned 2 white male patients (aged 36 and 42 years) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations that were resistant to diet regimens and lipid–lowering drugs. The patients were treated with low–density lipoprotein (LDL) apheresis for 59 months (Liposorber system, Kaneka, Japan) and 19 months (immunoadsorption system, special Lp(a) columns; Lipopak; Pocard, Russia), respectively. The concentration of Lp(a) decreased on average by 50%, total cholesterol by 27%, LDL cholesterol by 41%, triglycerides by 43%, and fibrinogen by 16%. High–density lipoprotein (HDL) cholesterol increased by approximately 4%. Before treatment with LDL apheresis, each patient had suffered 3 myocardial infarctions, and had had 4 and 6 coronary angiographies with 2 and 4 percutaneous transluminal angioplasties (PTCAs), respectively. Since treatment with LDL apheresis, no myocardial infarctions or cardiac complaints were observed. In the course of treatment, both patients reported an increased performance. Available data suggest that LDL apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being extremely elevated Lp(a) concentrations.     

氟伐他汀对糖尿病肾病中脂蛋白(a)水平的影响

目的：探讨氟伐他汀对糖尿病肾病中脂蛋白（a)水平的影响及其肾脏保护作用。方法：分别以糖尿病大鼠模型和2型糖尿病肾病患为研究对象，观察氟伐他汀治疗6周后血浆中脂蛋白（a)水平，组织型纤溶酶原激活物及其抑制剂活性，大鼠肾脏病理学改变。结果：与对照组比较，氟伐他汀治疗6周后糖尿病肾病患和大鼠体内脂蛋白（a)，尿白蛋白水平均降低，患纤溶酶原激活物抑制剂活性下降，纤溶酶原激活物活性上升，大鼠肾脏组织光镜及电镜下病变明显减轻。结论：氟伐他汀能下调脂蛋白（a)，减轻肾脏肥大，具有肾脏保护作用。     

Serum lipoprotein (a) concentration in patients with chronic renal failure receiving haemodialysis: influence of apolipoprotein (a) genetic polymorphism

Serum lipoprotein(a) (Lp(a)) was measured in 101 men with end-stagechronic renal failure (CRF) receiving haemodialysis and in 101age-matched male controls. Apolipoprotein(a) genetic polymorphismwas determined by immunoblotting in 100 patients and in 92 controls.Patients with CRF on haemodialysis had significantly greaterserum Lp(a) than controls. Apolipoprotein(a) phenotype frequenciesin patients with CRF did not differ from those of the controlgroup. Both patients and controls with phenotype S2 had greaterserum Lp(a) than those with phenotype S4. It should be emphasizedthat serum Lp(a) was significantly greater in patients on haemodialysisthan controls, both for those with phenotype S2 and those withS4. Increased serum Lp(a) together with other lipoprotein abnormalitiesin patients with CRF on haemodialysis imply an increased cardiovascularrisk. Genetic polymorphism clearly influences serum Lp(a) bothin controls and patients. In the latter group CRF itself, dialysis,or both, also play a role in increasing Lp(a).     

The Impact of Pre-Dialytic Endurance Training on Nutritional Status and Quality of Life in Stable Hemodialysis Patients (Sawada Study)

Background. Protein-energy malnutrition and decreased quality of life (QOL) are common in hemodialysis (HD) patients. Although several studies have proved that regular exercise has beneficial effects, few control studies have shown the effects of exercise training on the nutritional status and QOL in HD patients. Methods. Fifty-five HD patients were recruited, and 22 of them were trained to exercise on an ergometer prior to dialysis three times a week for one year. Serum albumin levels, creatinine generation rate (CGR), and the Short Form 36 were assessed as outcome measures. Results. The serum albumin levels and CGR increased in the training group compared with baseline. The QOL scores also increased in half of the physical health and mental health dimensions in the training group. Conclusion. These observations suggest that low-dose, long-term pre-dialytic endurance training might reverse the poor clinical outcome by improving the nutritional status and QOL in HD patients.     

Effects of Thoracic Epidural Analgesia on Cardiovascular Function and Plasma Concentration of Free Fatty Acids and Catecholamines in the Dog

Increased plasma levels of free fatty acids (FFA), leading to increases in the myocardial oxygen demand, are seen after, for example, surgical stress, traumas and myocardial infarction. The present study was undertaken to investigate the cardiovascular effects of thoracic epidural analgesia (TEA) and the effect of TEA on the plasma concentration of FFA and catecholamines. In 10 sodium-pentobarbital-anaesthetized dogs the local anaesthetic agent bupivacaine was injected into the thoracic epidural space via a surgically introduced catheter. TEA markedly reduced heart rate, mean aortic blood pressure, left ventricular systolic blood pressure and dP/dtmax. TEA reduced the plasma concentration of FFA. The FFA-lowering effect was greatest when the FFA values were high. The effect of TEA on the plasma concentration of noradrenaline and adrenaline was inconsistent and seemed to be of minor importance for the haemodynamic and FFA effects of TEA. The study indicates that TEA, by its haemodynamic and FFA-lowering effects, may reduce myocardial oxygen demand.