Mediterranean diet improves dyslipidemia and biomarkers in chronic renal failure patients

Abstract

Dyslipidemia, oxidative stress (OS) and inflammation increase the risk of cardiovascular disease in chronic renal failure (CRF) patients. The aim of this study was to evaluate the effect of nutritional advice on dyslipidemia and biomarkers in CRF patients. 40 CRF patients with dyslipidemia, hypertriglyceridemia and/or hypercholesterolemia were randomly assigned to either the control or the intervention group. The intervention group received nutritional advice adapted to a Mediterranean diet (MD). Patients were assessed at baseline (T0) and after 30 (T1), 60 (T2) and 90 (T3) days for dietary intake and biomarkers. In the intervention group compared to the control group, TG concentrations were decreased by 26% at T3 (p < 0.05), TC concentrations were diminished by 14% at T2 and by 35% at T3 (p < 0.05). A decrease in LDL-C was noted at T2 and T3 (p < 0.05). The TC/HDL-C ratio was diminished at T1, T2 and T3 (p < 0.05). The apo A-I/apo B ratio was elevated at T3 (p < 0.05). HDL-C, apo A-I, apo B concentrations and the TC/LDL-C ratio were similar in the both groups at T1, T2 and T3. Creatinine, urea, glomerular filtration rate (GFR), urate, iron and bilirubin values remained unchanged in both groups. Haemoglobin concentrations were elevated at T1 (p < 0.05). Increased albumin values were observed at T2 (p < 0.05). CRP concentrations were decreased by 29% at T1 (p < 0.05) and 40% (p < 0.01) at T3. Fibrinogen (p < 0.01) concentrations were decreased at T3. In the intervention group compared to control group (p < 0.01), TBARS values were decreased by 16% at T2 and 21% at T3 (p < 0.05). In this study, we demonstrate that the nutritional management of CRF patients before dialysis based on the MD improves food consumption, reduces dyslipidemia and protects against lipid peroxidation and inflammation, allowing patients to enter dialysis with an acceptable nutritional and cardiovascular state.

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Introduction

Recent advances in the pathophysiology of chronic renal failure (CRF) have highlighted the importance of dietary management of this disease. Indeed, despite continuous progress in the delivery of renal replacement therapy (RRT), new symptoms have appeared. Among them, undernutrition and cardiovascular diseases (CVD) hold a prominent place.

The increased prevalence of both CVD morbidity and mortality is evident at all ages among patients with CRF. Both traditional risk factors, including diabetes, dyslipidemia and hypertension, and non-traditional risk factors associated with CRF, including inflammation, oxidant stress and malnutrition, may further increase CVD risk.^1–3

Dyslipidemia enhances lipid peroxidation and activates free radical reactions.² Hypertriglyceridemia, hypercholesterolemia and elevated levels of low-density lipoprotein-cholesterol (LDL-C) are identified as key factors for CVD risk in CRF patients. Observational and epidemiological data have suggested the potential predictive role of C-reactive protein (CRP) in coronary heart disease.^4–6

Beneficial outcomes can be strengthened through dietary interventions. Nutritional intervention plays a major role in preserving the overall well-being of CRF patients. In preparation for RRT, dietary monitoring aims to reduce cardiovascular risk factors, prevent malnutrition and slow the progression of renal disease,^1–3 all of which can contribute to positive outcomes for patients. There are several potential advantages to prescribing a carefully designed low-protein diet (0.75 g kg⁻¹ BW d⁻¹) for the treatment of CRF patients.⁷ Low-protein diets reduce the generation of nitrogenous wastes and inorganic ions, which cause many of the clinical and metabolic characteristics of uremia. Moreover, low-protein diets can diminish the effects of hyperphosphatemia, metabolic acidosis, hyperkalemia and other electrolyte disorders that are the consequence of renal function loss.⁷

During the past decade, a large body of evidence has related the adherence to a Mediterranean diet (MD) to a decrease in all the causes of mortality, as well as the incidence of coronary heart diseases.⁸ An MD has long been recommended for its antiatherosclerotic properties.⁹ Among the effects of an MD diet, the suppression of lipoprotein peroxidation¹⁰ and the normalization of endothelial function are observed.^11,12 Such diets do not need to be restricted in total lipid intake as long as there is no excess of energy intake over expenditure and vegetable oils are emphasized as the main source of lipids, which are low in saturated fats and partially hydrogenated oils.¹³ The traditional MD includes the high consumption of olive oil, legumes, unrefined cereals and cereal products (whole grain bread, pasta and brown rice), fruits and vegetables, the moderate to high consumption of fish and dairy products (cheese and yogurt), the low consumption of meat and meat products, and moderate wine consumption.^14,15 The ratio of monounsaturated (MUFA) to saturated fats is much higher in the MD than in other places of the world, including northern Europe and North America.^14,15

The aim of this study is to evaluate the effect of appropriate nutritional advice based on the MD, on feeding, dyslipidemia and biomarkers in dyslipidemic CRF patients. We hypothesize that nutritional management based on a healthy and varied diet will enhance food intake and reduce cardiovascular risk through an adjustment of dyslipidemia and biomarker abnormalities, suggesting that an MD diet may have a preventive role against CVD.

Subjects and methods

Subjects

A prospective randomized trial study was carried out from January to April 2008 in the hospital of Oran (west of Algeria). Undialyzed patients were included on the basis that they had a moderate CRF with a glomerular filtration rate (GFR) of 60–89 mL min⁻¹ and dyslipidemia (triacylglycerols > 1.7 mmol L⁻¹) and/or total cholesterol > 5 mmol L⁻¹). Subjects were excluded on the basis that they had diabetic nephropathy, thyroid disease, and the use of anti-inflammatory drugs or antioxidants and vitamins. Creatinine clearance was estimated from serum creatinine using the Cockroft and Gault formula [GFR = (140-age) × BW × 1.23/creatinine]. In women, this value was multiplied by 0.85.¹⁶ From the 80 patients screened, 40 patients (M/F, 22/18) aged 61 ± 14 years were recruited for the study. CRF in patients was caused by chronic glomerulonephritis (n = 22), vascular nephropathy (n = 8), cystic kidney disease (n = 3) and unknown (n = 7). The demographic and medical characteristics of the population studied are presented in Table 1. Patients consented to participate in the study and were randomized into two groups: the intervention group, which underwent nutritional intervention (n = 20), and the control group (n = 20), which did not receive modified nutritional advice.

Table 1 Clinical characteristics of the patients^a

	CRF patients	Control group	Intervention group
a Data are expressed as mean ± standard error. BMI: body mass index (weight kg/height m^2); SBP: systolic blood pressure; DBP: diastolic blood pressure.
Patients (n)	40	20	20
Age/years	61 ± 14	59 ± 12	60 ± 10
Weight/kg	74 ± 15	73 ± 11	76 ± 14
BMI	26.2 ± 5.6	25.1 ± 4.2	26.9 ± 3.9
Sex ratio (M/F)	22/18	10/10	11/9
Smokers (%)	32	29	30
Employed (%)	50	45	38
SBP/mm Hg	125 ± 10	135 ± 8	128 ± 11
DBP/mmHg	84 ± 1	80 ± 2	83 ± 2
Glucose/g L^−1	0.90 ± 0.06	0.86 ± 0.01	0.95 ± 0.02
Triacylglycerols/mmol L^−1	3.8 ± 0.1	3.2 ± 0.3	3.8 ± 0.1
Total cholesterol/mmol L^−1	6.1 ± 0.7	6.5 ± 0.4	6.1 ± 0.7

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Nutritional intervention

All patients received nutritional advice based on the NKF K/DOQI (National Kidney Foundation—Kidney Disease Outcomes Quality Initiative) guidelines⁷ (energy intake of 0.12 MJ kg⁻¹ BW d⁻¹, protein intake 0.75 g kg⁻¹ BW d⁻¹, lipid intake 35% and carbohydrates 55% of total energy intake). In the intervention group, dietary recommendations were modified and adapted to a MD, with increased intake of MUFA, PUFA and fibers. To achieve this objective, the subjects were asked to consume olive oil and nuts for seasonings, whole grains (50 g of bread at each meal, 250 g of cereal or starch once a day), fruits (once a day), vegetables (200 g twice daily) and fish (twice a week). A list of foods rich in salt, potassium and phosphorus was provided. In addition, patients received advice about the cooking methods best suited for adherence to a MD.

To control the recommendation monitoring, nutritional surveys were carried out at baseline and at 30 (T1), 60 (T2) and 90 (T3) days after the beginning of nutritional intervention.

All patients received intervention instructions at the Nephrology ward of the University Hospital of Oran. The purpose of this study was explained to the subjects, and the investigation was carried out with their consent. The experimental protocol was approved by the Committee for Research on Human Subjects of Oran.

Dietary survey methods

The food consumption survey used the method of “recall and record”, repeated every 4 days. Patients were interviewed by trained interviewers using an adapted and structured questionnaire. Each subject was asked to recall everything they had eaten or drunk during the 24 h preceding the interview. The day was chronologically organized into breakfast, lunch and dinner. The meals were structured by entry, principal dish, accompaniments, bread and drinks. The interview was organized with specific questions about the ingredients and methods of preparation, and the additions usually served with a meal, such as butter, milk in coffee and mayonnaise. Subjects were also asked to list the names and quantity of consumed food that was not spontaneously reported. Serving sizes were estimated by the use of the food portion model handbook. Dimensions of dishes, utensils and foods were measured, and the portion sizes were estimated accurately. The consumed foods were converted into various nutrients using the software GENI.¹⁷

Assays

In all patients’, blood samples were drawn after a 12 h overnight fast by antecubital venipuncture at the beginning (T0), 30 (T1), 60 (T2) and 90 (T3) days after initiating nutritional intervention. Samples were collected and subjected to low speed centrifugation at 3000 × g at 5 °C for 15 min. They were then preserved with 0.1% Na₂ EDTA and 0.02% sodium azide.

Triacylglycerols (TG) and total cholesterol (TC) were determined by colorimetric methods (BioMérieux Kits, France). Urea and creatinine were analyzed by colorimetric methods (Kits Biocon). Serum high-density lipoprotein-cholesterol (HDL-C) was determined enzymatically using a CHOD-PAP kit after precipitation of the chylomicrons, very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) with phosphotungstic acid and Mg²⁺ (BioMérieux Kits, SA-France). Serum LDL-C was determined enzymatically using a CHOD-PAP kit after precipitation of LDL. Serum apolipoproteins (apo) A-I and B were measured by the immunoturbidimetric method (Human kit, Allemagne). Serum lipid peroxidation was estimated by measuring the concentrations of thiobarbituric acid reactive substances (TBARS) according to the method of Quintanilha et al.,¹⁸ using tetramethoxypropane (Prolabo) as a precursor of malondialdehyde. C-Reactive Protein (CRP) was measured by the immunoturbidimetric method (Fumouze, France). Colorimetric methods were used for the determination of albumin, urate (Kits Boehringer, Mannheim, Germany), iron and bilirubin (Biolabo kits, France). Fibrinogen levels were measured using automatic nephelometry.

Statistical analysis

Values are presented as mean and standard error. Data normality and distribution of the variables were tested by the Kolmogorov-Smirnov test. The difference between the means from the different groups was checked by ANOVA adjusted for multiple comparisons. Differences between groups at the same time point were analyzed using Mann Whitney's test, whereas differences within groups at different time points were analyzed using Wilcoxson's test. Levels of p < 0.05 were considered significant. Linear regression analysis was used to determine correlation coefficients between food intake, dyslipidemia and biomarker values. The calculations were performed using STATISTICA 6.0 (for Windows, StatSoft Inc. software, Tulsa, OK, USA).

Results

Food intake composition

A significant increase in total energy intake (TEI) (Table 2) was noted in the intervention group compared to the control group at T2 and T3 (p < 0.05). These intakes were also increased compared to T0 (p < 0.05). An unbalanced energy distribution was noted at T0. Expressed as a percentage of TEI, protein, carbohydrate and lipid intakes represented, respectively, 8, 65 and 27% at T0. Similar protein intakes were noted at T1, T2 and T3 in the intervention group compared to the control group. Carbohydrate intake was increased at T3 in the intervention group compared to control group and to T0 (p < 0.05). Lipid intake was increased at T2 and T3 in the intervention group compared to control group and to the baseline value T0 (p < 0.05).

Table 2 Food intake composition^a

	Baseline	Control group			Intervention group			DR
	T0	T1	T2	T3	T1	T2	T3
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. DR: dietary recommendations. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05.
TEI/MJ	6.8 ± 0.3	6.0 ± 1.5	6.1 ± 0.3^c	6.1 ± 0.2^c	7.5 ± 0.6	7.9 ± 0.4^d	7.6 ± 0.1^d	8
Proteins/MJ	0.6 ± 0.02	0.60 ± 0.1	0.6 ± 0.01	0.6 ± 0.04	0.6 ± 0.07	0.7 ± 0.09	0.7 ± 0.07	0.8
% of TEI	8	9	9	9	9	9	10	10
Carbohydrates/MJ	4.1 ± 0.1	4.2 ± 2.1	3.9 ± 0.2	3.3 ± 0.1^c	4.5 ± 0.2	4.3 ± 0.1	4.4 ± 0.1^d	4.4
% of TEI	65	70	63	64	60	56^b	55^b	55
Lipids/MJ	1.8 ± 0.1	1.3 ± 0.6	1.9 ± 0.2^c	1.9 ± 0.2	2.4 ± 0.2	2.7 ± 0.2^d	2.6 ± 0.3^d	2.8
% of TEI	27	21	28	27	32	35^d	35^d	35

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An improvement in animal protein intake (Table 3) was noted only at T3 in the intervention group compared to the controls and to T0 (p < 0.05). In parallel, the consumption of vegetable protein decreased at T1 and T3 compared to the controls (p < 0.05). An increase in sugar intake was noted at T2 and T3 (p < 0.05) in the intervention group compared to the control group. Starch consumption decreased at T3 in the intervention group compared to the control group and to T0 (p < 0.05). Fiber and cholesterol intakes were in accordance with nutritional requirements. PUFA and SFA intakes were, respectively, lowered and increased at T1, T2 and T3 in the intervention group compared to the control group (p < 0.05). An increase in MUFA intake was noted at T2 and T3 (p < 0.05). In the intervention group, a decrease was noted in PUFA intake at T1, T2 and T3 compared to T0 (p < 0.05).

Table 3 Qualitative food intake^a

	Baseline	Control group			Intervention group			DR
	T0	T1	T2	T3	T1	T2	T3
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. DR: dietary recommendations. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05.
Animal (%)	38	41	55	69	58^c	52	57^d	60
Vegetable (%)	62	59	45	31	42^b	48^c	43^d	40
Sugar (%)	18	20	19	21	25	30^b	29^b	40
Starch (%)	82	80	81	79	75	70^c	61^d	60
Fiber/g	36	35	30	29	35	34	33	30
PUFA (%)	30	35	32	30	25^d	26^d	23^d	25
MUFA (%)	37	36	35	33	38	44^b	49^d	50
SFA (%)	33	29	23	37	37^b	30^b	28^b	25
Cholesterol/mg	180	190	175	225	230	225	228	<300

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At T3, the qualitative distribution of nutrients had a tendency to be closer to the recommended diet. In the intervention group compared to the control group (Table 4), a high consumption of cooked vegetables, fruit, bread, cereals, rice, pasta, milk and dairy products was noted at T3 in the intervention group compared to the control group (p < 0.05). However, a significant decrease was noted in fat intake at T3 (p < 0.01) in the intervention group compared to the control group and to T0 (p < 0.05).

Table 4 The intake of food groups^a

Food group	Baseline	Control group			Intervention group			DR
	T0	T1	T2	T3	T1	T2	T3
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. DR: dietary recommendations. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05.
Cooked vegetables and fruit	255 ± 66	230 ± 15	238 ± 72	238 ± 65	262 ± 85	393 ± 108	462 ± 99^d	500
Bread, cereals, rice and pasta	278 ± 55	270 ± 95	267 ± 56	298 ± 15	302 ± 26	326 ± 89	411 ± 85^b	400
Milk and dairy products	85 ± 9	95 ± 14^c	99 ± 28^c	95 ± 12	121 ± 14^c	137 ± 14^c	160 ± 35^d	180
Meat, poultry and fish	35 ± 12	32 ± 4.0	39 ± 23	45 ± 10	40 ± 0.64^b	48 ± 14	70 ± 25	50
Raw vegetables and fruits	125 ± 26	130 ± 75	139 ± 13	167 ± 62	138 ± 15	198 ± 10^d	255 ± 92	50
Fat	80 ± 12	85 ± 12	79 ± 32	95 ± 15	77 ± 25	45 ± 33	55 ± 0.75^c	60
Sweet products	95 ± 18	87 ± 13	79 ± 8.6	89 ± 8	78 ± 22	69 ± 8.6	59 ± 16	60

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Lipids and apolipoproteins

A decrease by 26% in TG concentration was noted at T3 (Table 5) in the intervention group compared to the control group, and by 9% compared to T0 (p < 0.05). The TC concentration was diminished by 14% at T2 and by 35% at T3 (p < 0.05) in the intervention group compared to the control group. At T3, values of TC were lower than at T0 (p < 0.05). A decrease in LDL-C was noted at T2 and T3 (p < 0.05) in the intervention group compared to the control group. These values were lower at T3 compared to T0 (p < 0.01). The TC/HDL-C ratio was diminished at T1, T2 and T3 in the intervention group compared to the control group (p < 0.05) and to T0. The apo A-I/apo B ratio was elevated at T3 in the intervention group compared to the control group and to T0 (p < 0.05). HDL-C, apo A-I and apo B concentrations, and the TC/LDL-C ratio, were similar in both groups at T1, T2 and T3.

Table 5 Baseline levels and the effect of 3 months of nutritional intervention on serum lipids^a

	Baseline	Control group			Intervention group
	T0	T1	T2	T3	T1	T2	T3
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05. e p < 0.01.
TG/mmol L^−1	3.2 ± 0.3	2.8 ± 0. 6	3.0 ± 0.1	3.9 ± 0.1	3.4 ± 0.4	3.1 ± 0.8	2.9 ± 0.1^d
TC/mmol L^−1	6.5 ± 0.4	5.3 ± 1.0	6.3 ± 1.0	5.4 ± 0.4	6.1 ± 0.02	5.4 ± 0.9^b	4.1 ± 0.5^d
HDL-C/mmol L^−1	2.1 ± 0.5	2.7 ± 0.2	2.5 ± 0.2	3.0 ± 0.2	2.5 ± 0.2	2.5 ± 0.4	2.8 ± 0.6
LDL-C/mmol L^−1	3.5 ± 1.0	3.3 ± 0.2	3.6 ± 0.2	3.0 ± 0.2	3.6 ± 0.2	2.8 ± 0.1^b	2.0 ± 0.02^b^,^e
Apo AI/g L^−1	0.9 ± 0.2	1.2 ± 0.6	1.3 ± 0.6	1.3 ± 0.5	1.3 ± 0.1	1.1 ± 0.1	1.2 ± 0.1
Apo B/g L^−1	0.9 ± 0.1	1.0 ± 0.2	1.0 ± 0.3	1.0 ± 0.1	1.1 ± 0.1	1.1 ± 0.3	1.0 ± 0.1
TC/HDL-C	2.9 ± 0.1	2.6 ± 0.1	2.8 ± 0.2	2.7 ± 0.4	2.1 ± 0.2^d	1.8 ± 0.1^d	1.7 ± 0.2^b^,^e
TC/LDL-C	2.1 ± 0.2	2.6 ± 0.8	2.3 ± 0.1	2.3 ± 0.4	2.8 ± 0.9	3.2 ± 0.1^d	2.1 ± 0.5
Apo AI/Apo B	0.8 ± 0.1	1.5 ± 0.5	0.9 ± 0.1	1.1 ± 0.2	1.6 ± 0.4	0.8 ± 0.4	1.8 ± 0.1^d

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Renal function and biomarkers

Creatinine, urea, GFR, urate, iron and bilirubin values remained unchanged in both groups (Table 6). Haemoglobin concentrations were elevated at T1 in the intervention group compared to the control group and to T0 (p < 0.05). Increased albumin values were observed at T2 (p < 0.05) in the intervention group compared to T0. CRP concentrations decreased by 29% at T1 (p < 0.05) and by 40% at T3 (p < 0.01) in the intervention group compared to the control group. A decrease in the CRP level was noted in the intervention group at T3 compared to T0 (p < 0.05). Fibrinogen concentrations decreased at T3 (p < 0.01) in the intervention group compared to the control group (p < 0.01) and to T0 (p < 0.05). TBARS values decreased by 16% at T2 and by 21% at T3 in the intervention group compared to the control group. These values were lower compared to T0 (p < 0.05).

Table 6 Baseline levels and the effect of 3 months of nutritional intervention on renal function and serum biomarkers^a

	Baseline	Control group			Intervention group
	T0	T1	T2	T3	T1	T2	T3
a T0: the beginning of nutritional intervention; T1, T2 and T3: 30, 60 and 90 days after initiating nutritional intervention. Data are presented as mean ± standard error. b Significant difference between groups at the same time point (Mann Whitney's test). c Significant difference in relation to the baseline (Wilcoxon's test). d p < 0.05. e p < 0.01.
Creatinine/μmol mL^−1	189.0 ± 70.0	150.0 ± 49.0	169.0 ± 49.0	110.0 ± 33.0	151.0 ± 57.0	170.0 ± 56.0	109.0 ± 47.0
Urea/mmol L^−1	14.2 ± 4.8	12.0 ± 5.0	12.0 ± 2.1	11.8 ± 4.4	11.0 ± 4.8	11.5 ± 3.0	12.1 ± 3.4
GRF/mL L^−1	75.0 ± 15.0	69.0 ± 9.0	72.0 ± 6.0	75.0 ± 8.0	70.0 ± 10.0	72.0 ± 6.0	77.0 ± 0.9
Urate/mmol L^−1	0.4 ± 0.1	0.4 ± 0.1	0.4 ± 0.1	0.6 ± 0.2	0.6 ± 0.1	0.5 ± 0.1	0.6 ± 0.1
Iron/μmol L^−1	33.0 ± 17.7	38.1 ± 15.0	35.0 ± 0.1	37.2 ± 0.8	36.0 ± 0.1	34.6 ± 0.1	35.1 ± 0.3
Bilirubin/μmol L^−1	6.2 ± 2.6	5.6 ± 2.1	7.0 ± 0.1	8.1 ± 0. 7	7.3 ± 0.1	6.8 ± 1.3	7.6 ± 0.1
Haemoglobin/g dL^−1	12.1 ± 0.1	10.0 ± 0.1^c	12.9 ± 0.1	14.1 ± 2.2	13.5 ± 0.1^d	13.9 ± 1.1	13.9 ± 5.0
Albumin/g L^−1	32.2 ± 5.0	30.4 ± 6.0	35.0 ± 2.1	38.0 ± 10.0	38.0 ± 6.3	42.2 ± 5.0^c	44.1 ± 5.2
CRP/mg L^−1	6.5 ± 0.9	7.0 ± 0.2	7.8 ± 0.8	7.0 ± 0.1	6.4 ± 0.1^b	5.8 ± 1.0	4.2 ± 0.2^e
Fibrinogen/g L^−1	3.5 ± 0.7	3.0 ± 0.7	3.2 ± 1.9	3.4 ± 0.9	2.9 ± 0.5	2.9 ± 1.5	2.0 ± 0.1^e
TBARS/μmol L^−1	8.4 ± 0.5	9.5 ± 0.2	8.0 ± 0.7	7.8 ± 0.3	7.9 ± 1.5	6.7 ± 0.3^d	6.3 ± 0.01^d

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Correlation analyses

In the intervention group, inverse relationships were noted between MUFA intake and TC concentration (r = −0.59, p < 0.01) and LDL-C (r = −0.55, p < 0.01). TBARS and CRP concentrations were negatively correlated with cooked, vegetables and fruit intakes (r = −0.60, p < 0.01).

Discussion

This study was undertaken in order to evaluate the effect of nutritional advice based on the principles of an MD on dyslipidemia and serum biomarkers in undialyzed CRF patients. During follow-up, food intake and serum biomarkers were assessed at baseline, 30, 60 and 90 days after initiating intervention. A favorable effect on renal function, represented by a stable GFR, was observed. Recent findings have shown that greater adherence to an MD is independently associated with reduced urea and creatinine, and increased creatinine clearance rates, among healthy men and women.¹⁹ Similarly, we showed in a recent study that renal function was not altered by three-month balanced diet intervention.²⁰ This investigation showed that in CRF patients with moderate dyslipidemia, the monitoring of nutritional intake lead to a decrease in TG, TC and LDL-C after 90 days of intervention. Some recent studies have highlighted the beneficial role of an MD on lowering hypertriglyceridemia.^19,21,22 In the ATTICA study, the authors established that biochemical and clinical markers were affected favorably by such a diet.^19,21,22 Moreover, it has been shown that whole-grain intake is inversely correlated with triacylglycerol concentration.²³ In our previous work carried out on haemodialysis patients, hypertriglyceridemia was found to be moderate as compared to its prevalence in developed countries. This could be due to the diet consumed by our population, which was characterized by a high intake of vegetable proteins, complex carbohydrates, fiber and MUFAs.^24–26 A negative correlation was noted between MUFA intake and TC in the intervention group. Olive oil, as the major source of MUFAs, exerts an antioxidant action and suppresses the release of arachidonic acid from the lipid constituents of cell membranes.⁹ The results of our study confirmed that significant changes in serum lipids could be induced by modest dietary modifications. In this study, we used serum TBARS as a marker of OS, and CRP as an inflammation marker. TBARS levels were diminished after 3 months of initiating dietary intervention. Serum lipids were protected against OS by dietary components such as polyphenols and MUFA. The finding that the TBARS concentration was inversely related to cooked vegetable and fruit intake suggests that the key role in protecting lipids against peroxidation is played by some factor(s) present in the diet other than oleic acid. Such an effect may be achieved by polyphenols contained, for example, in cold-pressed olive oil, fruit and vegetable.

It has been shown that there is an association between elevated CRP levels and the risk of cardiovascular events and peripheral vascular disease that is independent of traditional risk factors.^4–6 In our study, the CRP level was greater than 5 mg L⁻¹ at the beginning of the study and then was modified by the diet. Elevated serum CRP levels are correlated with increased risk of death due to stroke.⁴ With levels of CRP above 5.5 mg L⁻¹, the risk is 1.67-times higher than that at levels below 2.1 mg L⁻¹; moreover, this is independent of other risk factors.⁴ In our patients, CRP concentrations were inversely associated with cooked vegetables, fruit and fish; fish being the best source of omega-3 fatty acids. Indeed, in our patients, sardines were the most frequently consumed fish (twice a week). A strong inverse relationship was found between fish consumption and levels of inflammatory markers related to CV.²² Similarly, it has been demonstrated that a greater adherence to a traditional MD is independently associated with a reduction in CRP and fibrinogen levels.²¹ The association between elevated plasma fibrinogen and coronary risk may also partly reflect an ongoing inflammatory process.²⁷ However, the exact association between these proinflammatory markers and diet was not clear. Therefore, because fish consumption has been associated with decreased concentrations of these proinflammatory markers, it can be suggested that regular fish intake may suppress inflammation and have beneficial effects on human health. Recently, we also showed that omega-3 fatty acid supplementation (2.1 g day⁻¹) was inversely associated with hypertriglyceridemia and CRP in CRF patients eating a balanced diet.²⁰ Zampelas et al. (2005)²² suggested that the benefit is more pronounced if omega-3 fatty acids are consumed in the form of fish rather than in the form of a supplement.

In conclusion, the nutritional management of CRF patients before dialysis based on an MD improves food consumption, reduces dyslipidemia and protects against lipid peroxidation and inflammation, allowing patients to enter dialysis with an acceptable nutritional and cardiovascular state.

Acknowledgements

This work was supported by the National Agency of Health Research (ANDRS no 02/15/01/01/084).

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