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Clinical Nephrology, Vol. 64 – No.

2/2005 (103-112)

Cardiovascular risk factors in severe chronic
renal failure: the role of dietary treatment
F. Bergesio1, G. Monzani2, A. Guasparini3, R. Ciuti4, M. Gallucci5, C. Cristofano6,
E. Castrignano7, A. Cupisti8, G. Barsotti8, R. Marcucci9, R. Abbate9, S. Bandini1,
Original M. Gallo1, P.L. Tosi2 and M. Salvadori1
©2005 Dustri-Verlag Dr. K. Feistle
ISSN 0301-0430
1Department of Nephrology, Dialysis and Transplantation, Azienda Ospedale

Careggi, Florence, 2Renal Unit Ospedale di Torregalli, Azienda Sanitaria Firenze,
Florence, 3Dietary Service, 4Clinical Chemistry, Azienda Ospedale Careggi,
Florence, 5Renal Unit Ospedale di Galatina, Azienda Ospedale Galatina,
6Renal Unit Ospedale di Manduria, Azienda Ospedale Manduria,
7Renal Unit Ospedale di Campi salentina, Azienda Ospedale di Campi Salentina,
8Nephrology Unit, Department of Internal Medicine, University of Pisa,
9Thrombosis Center, University of Florence, Florence, Italy

Cardiovascular risk factors in patients with end-stage renal disease

Key words Abstract. Background: Lipoprotein ab- < 0.05) were also observed in these patients.
cardiovascular risk fac- normalities and increased oxidized LDL Concentrations of vitamin E and A were not
tors – chronic renal fail- (OxLDL) are often observed in uremia and different between the two groups while vita-
ure – C-reactive protein are reported to play a central role in the devel- min B12 and folic acid resulted markedly in-
(CRP) – low-protein diet opment of cardiovascular disease (CVD). creased in patients on VSD. OxLDL signifi-
– vegan diet – oxidative Vegan diet, known for its better lipoprotein cantly correlated with total and LDL choles-
stress – Lp(a) – homo- profile and antioxidant vitamins content, terol, triglycerides and Apo B in CD but not in
cysteine – LDL choles- could protect against CVD. Aim of this study VSD patients. Patients on CD also showed a
terol – oxidized LDL
was to investigate the influence of vegan diet significant correlation between urea and CRP.
supplemented with essential amino acids After a multivariate analysis, only urea (p <
(EAA) and ketoanalogues (VSD) on both tra- 0.001) and OxLDL (p < 0.006) were associ-
ditional and non-traditional cardiovascular ated to a risk of CRP > 0.3 mg/dl. Conclu-
risk factors (CVRF). Methods: Twenty-nine sions: These results indicate a better lipopro-
patients (18 M, 11 F) aged 55 years (range tein profile in patients on vegan diet including
29 – 79 years) with advanced chronic renal non-traditional CVRF. In particular, these pa-
failure (median sCr: 5.6 mg/dl) on very low tients show a reduced oxidative stress with a
protein vegetarian diet (0.3 g/kg/day) supple- reduced acute-phase response (CRP) as com-
mented with a mixture of EAA and ketoacids pared to patients on conventional diet. We hy-
(VSD) and 31 patients (20 M, 11 F) aged 65 pothesize that urea, significantly lower in pa-
years (range 29 – 82 years) on conventional tients on VSD, may account, possibly to-
low-protein diet (CD: 0.6 g/kg/day) with a gether with the reduction of other protein
similar renal function (median sCr: 5.2 breakdown products, for the decreased
mg/dl), were investigated for lipids and apo- acute-phase response observed in these pa-
lipoprotein parameters (traditional CVRF) as tients. Our findings suggest that low-protein
well as for oxidative stress (oxidized LDL, diets, and vegan in particular, may exert a
antibodies against OxLDL and thiobarbituric beneficial effect on the development of car-
acid-reactive substances (TBARS)), total diovascular disease in patients with end-stage
homocysteine (tHcy), lipoprotein(a) (Lp(a)), renal disease (ESRD).
albumin and c-reactive protein (CRP) (non-
traditional CVRF) including vitamins A, E,
B12 and folic acid. Results: Compared to pa-
tients on CD, those on VSD showed increased Introduction
June 1, 2004;
HDL cholesterol levels (p < 0.005) with a re-
accepted in revised form
December 6, 2004
duction of LDL cholesterol (p < 0.01) and an Patients with chronic renal disease show a
increase of apoA1/ apoB ratio (p < 0.02). high prevalence of morbidity and mortality
Correspondence to Among non-traditional CVRF, a mild but sig-
for atherosclerotic cardiovascular disease
Dr. F. Bergesio nificant reduction of OxLDL (p < 0.05) with
lower TBARS concentrations (p < 0.01) and a (CVD] [Foley et al. 1998]. Among risk fac-
Via del Pino, 50137
Firenze, Italy significant reduction of total homocysteine (p tors for CVD, hyperlipidemia has been indi- < 0.002), Lp(a) (p < 0.002) and CRP levels (p cated to play a major role in the development

the atherosclerotic process and in predicting versely. 2002]. 1992. Patients ent cardiovascular risk factors both in general population and in uremics [Moustapha et al. Patients with . Maggi et al. tes mellitus. Besides lipids peroxida. Rauma and Mykkanen 2000]. Monzani. Guasparini et al. auto. ther levels of OxLDL or OxLDLAb in pa- tients with renal failure [Bergesio et al. 2000. above factors in uremia. diabe- [McCarthy 1999. cross-sectional study. protein profile including Lp(a). male patients with chronic uremia [Barsotti et matory reaction within the arterial wall whose al. (CD) were considered for this observational cated by a more favorable BMI. 1998. in a recent prospective ulation and in uremia [Ridker and Haughie study where they found an inverse associa. 2002. circulating OxLDL were found The aim of our study is to investigate the to be elevated in patients affected by CVD influence of vegan-supplemented diet (VSD) suggesting they might represent a possible versus conventional low-protein diet (CD) on risk marker for the disease [Toshima et al. on immunosuppressive or steroid therapy tamin status (vitamins C. total homocysteine. namely oxidized low-density lipo. 2001. to improve serum total cholesterol and glucose gering event in this process [Witztum 1994]. Ritter and Richter 1995. gathered about the role of acute-phase pro- workers to be an independent predictor of the teins. 1984]. rocyte membranes has been pointed out in stance. alcohol abuse. and b-carotene). et al. 1997]. malignancy or contribute to maintain a higher antioxidant vi. plemented diet (VSD) or conventional diet ficial effect in the general population as indi. To date. a better lipid and apolipo- mation [Kaplan and Aviram 1999]. However. (vegan-supplemented diet (VSD)) was found protein (OxLDL). nal failure and to reduce triglyceride levels in attractant for monocytes inducing an inflam. few and conflicting results risk factors (CVRF) in patients with ad- have been available concerning the role of ei. Yeun et al. Shojiet et al. Patients on lipid-lowering thus preventing lipid peroxidation [Hostmark treatment entered the study after a wash-out et al. Up to now. More recently. no data are tion between autoantibodies against OxLDL available about the influence of diet on the and mortality from CVD [Shoji et al. 1981. 1989]. Ciardella et al. final event is the atherosclerotic plaque for. obesity (BMI > 30). protein profile and a lower blood pressure Patients with nephrotic syndrome. traditional and non-traditional cardiovascular 2000]. vegan diet was reported to exert a bene. namely C-reactive protein (CRP). much evidence has been cross-sectional study by Salonen and co. a better lipo. tre and a reduced lipid peroxidation of eryth- rence of LDL oxidation in vivo like. OxLDLAb ti- much evidence was produced for the occur. In addition. levels unless the diet is supplemented with vi- Yla-Herttuala et al. Materials and methods tion. 2000]. 1988. 1993. 1992]. and progression of carotid atherosclerosis in reduced albumin levels in the development of Finnish men [Salonen et al. endocrine or Rouse et al.5 mg/dl) either on vegan-sup- CVD. for in. 1988] and anti-OxLDL auto. with moderate to severe renal failure (serum According to the risk of development creatinine > 3. 1994]. Peuchant et al. tolerance in diabetic patients with chronic re- Indeed. antibodies against malondialdehydelysine. patients well as in the circulation of both rabbit and on vegan diet are reported to show increased man [Salonen et al.Bergesio. Mezzano et al. supplemented with EAA and ketoanalogues oxidation. OxLDL would act as a chemo. it would also liver diseases. they were suggested to exert a protec. In addition. lipoprotein a and C-reactive protein would all act as independ. would represent the trig. modified LDL (MDA-LDL) were found in a In the past years. Accordingly. vanced chronic renal failure. Accordingly very low protein vegan diet Attman and Alaupovich 1991]. Stable chronic renal failure outpatients 1998]. 2000]. period of at least eight weeks. Con. the demonstration of oxidized LDL patients on such a dietary regimen [Bergesio [Avogaro et al. Lipid per. 104 of atherosclerotic disease [Chan et al. were excluded. E. tamin B12 and B6 [Bissoli et al. cardiovascular mortality both in general pop- tive role by Shoji et al. 2001. 1986]. antibodies (OxLDLAb) in the arterial wall as Concerning homocysteine levels.

* normalized protein intake.3 g/kg/day) supplemented with a mixture Ethics Committee of the Florence Hospital. Calcium car. last six months were excluded as well. Conventional 6 – 120 months). mented with calcium carbonate. the possibility to switch to the (0. after a nutritional interview (20 – 29) (21 – 29) with a dietician and a clinical evaluation by a nPi* (g/kg/day) 0.5 : 1). Patients followed Table 1.6 p < 0.2 p < 0. assayed for determination of both traditional bonate and iron were administered when nec. A normalized protein catabolic rate (nPCR) of 0.001 nephrologist. C-reactive day and vitamin B6 between 2 – 250 mg ac. triglycerides (TG). Shire.5) (3. 29 31 protein restriction (0.000 g Patients were on this diet for a median time of for 5 min and the plasma analyzed for thio- 15 months (range 6 – 93 months).001 Dietary protein intake was estimated by (32 – 150) (56 – 147) calculation of protein catabolic rate (PCR) using Maroni’s formula [Maroni et al. acid ratio of 3. iron and folic creatinine and albumin were analyzed using a . of essential amino acids and ketoacids (ALFA KAPPA. proteins (8 – 10%).5/1). albumin. EDTA (1 mg/ml) were centrifuged at 3.5 – 10.6) (0. Methods scription was 30 – 35 Kcal/kg/day supplied by carbohydrates (63 – 67%). supplemented low protein p All centers participating in the study fol- diet diet lowed a similar dietetic approach consisting at first in prescribing patients a conventional Patient No. apolipo- B12 content ranged between 4 – 500 mg per proteins A1 and B.4 – 0. and non-traditional CVRF. overnight fast and then stored at –20 °C until rated fatty acid ratio of 2. protein. barbituric acid-reactive substances. All patients were supplemented with a were allowed to coagulate and the serum ana- mixture of B group vitamins in which vitamin lyzed for creatinine. Urea (mg/dl) 74 103 p < 0.9 g/kg/day was as- sumed as the upper limits of tolerance for pa- overt metabolic acidosis or weight loss in the tients respectively on VSD and CD (Table 1). Italy) at the dosage of one tablet per 5 – 8 kg/day VSD.4 – 10. Folic acid was not usually supplied.5) bolic control of the uremic syndrome. Cardiovascular risk factors in patients with end-stage renal disease 105 acid according to the need.9) vegan diet in order to obtain a better meta- sCr (mg/dl) 6. and 11 females aged 55 years (range 29 – 79 All selected patients gave their informed years) on very low protein vegetarian diet consent. lipids.6 g protein/kg/day). The study was approved by the local (0. fats (28 – 32% with an unsaturated/satu. compliant and motivated patients BMI (kg/m2) 25 24 were offered. males and 11 females aged 65 years (range 29 – 82 years) on conventional low-protein (0.6 g/kg/day) diet (CD).5 Gender (M/F) 18/11 20/11 mg/dl). On Age (years) 55 65 (29 – 79) (29 – 82) deterioration of renal function (sCr > 3. Energy pre.3 – 0. factors drates (55 – 60%). high-density lipoprotein cholesterol (HDL-C). fats (30 – 35% with unsaturated/saturated fatty Total cholesterol (TC). 1985]. LDL- The other group included 31 patients: 20 oxidized antigen and total homocysteine.02 (3. proteins (3 – Blood samples were collected after an 5%). vitamins A and E and antibodies cording to different commercially available against OxLDL. mentioned limits) were excluded from the One group included 29 patients: 18 males study. Characteristics of patients.5 5. Energy supply was Traditional cardiovascular risk 30 – 35 Kcal/kg/day. 5 ml of blood containing tablets.35 0. Firenze. supplied by carbohy. The diet was supple.6 g/kg/day and of 0. Patients with bad compliance to dietary Sixty patients on either of the two dietary prescriptions (mean value of the last three- treatments for at least six months were finally monthly determinations of nPCR over afore- selected to participate in the study. the diet for a median time of 30 months (range Vegan. according to Maroni’s formula. lipoprotein(a). 10 ml of blood essary.

Amer- ican Diagnostica Inc. Results 4E6 with the Mercodia oxidized LDL Elisa Kit (Mercodia. the absorbance of the organic phase was determined at 535 nm against blank [Richards 1992]. USA). IL. All data are reported as median values metry (Dade-Behring. LDL cholesterol (LDL- C) was calculated using the Friedewald for- mula. DE. New York. method using Cu(II)-oxidized LDL coated Concerning the traditional CVRF. USA) performed on ies raised against Lp(a). within range. Monzani. sex and BMI distribution were simi- al.3 mg/dl cardiovascular risk. Guasparini et al. risk factors Spearman’s rank correlation coefficient was employed for analysis of the relationship Albumin and C-reactive protein (CRP) between two variables. found in the group on vegan diet who also .Bergesio. Odds ratios for CRP > 0. 106 trophotometrically the reaction of serum with thiobarbituric acid mixed with 1% of tri- chloroacetic acid after heating for 30 min at 100 °C. serum Autoantibodies against oxidized LDL creatinine levels were slightly but signifi- (OxLDLAb) were determined by an ELISA cantly higher in VSD group (p = 0. Lipoprotein (a) was measured by an ELISA kit (Imubind Lp(a) ELISA Kit.02). The competitive immunoassay utilizes two tracers 57 °C for Figure 1. pa- onto microtiter strip as antigen (oLAB kit. Sweden) [Holvoet et Age.05 was consid- Analyzer (Abbott. The non-parametric Mann- Whitney U-test for unpaired data was used to compare each parameter between the two Non-traditional cardiovascular groups of patients. Newark. ered statistically significant. Vitamin B12 and folates were analyzed si- multaneously using a radioassay kit (ICN Pharmaceuticals Simul TRAC-SNB RIA. IL. on CD. Statistics Apolipoproteins A1 and B (Apo A1 and Apo B) were assayed by immunonephelo. DE. The chromogen was extracted with n-butanol. NY. USA) on Behring nephelometer parameters on CRP levels used as outcome considering value of 0. employed to evaluate the influence of several Newark. Austria) [Eber apolipoprotein profile compared to patients 1994]. Vienna. USA). 1998]. were determined by immunonephelometry A multiple linear regression model was using two high sensitivity kits (Dade Behring. On the contrary. lar in the two groups. Abbott Park. USA). Greenwick. were given with their 95% confidence inter- Total homocysteine (tHcy) was evaluated val and were computed by multivariate logis- in plasma using an FPIA technique on Imx tic regression analysis. CT. USA) standard technique and commercial kits from utilizing affinity purified polyclonal antibod- Abbott (Abbott Park. OxLDL antigen (OxLDL) was measured by a competitive ELISA method utilizing a specific murine monoclonal antibody. In particularly higher HDL-C levels Thiobarbituric acid-reactive substances with a significant reduction of LDL-C were (TBARS) were determined evaluating spec. Vitamins A and E were determined by HPLC-UV method. vitamin B12 and 125I for folates. Uppsala. a p < 0. mAb. Aeroset instrument.3 mg/dl as a cut-off for variable. tients on VSD showed a better lipid and Biomedica-Gruppe. Traditional cardiovascular risk factors.

28 0. Lp(a) and nutritional parameters such as urea.25 0.3 mg/dl (Table 5). the differences of CRP.52 0. and oxidative stress.50 0. In this model. Apo-B in both groups of patients.54 – 0. play higher levels of vitamin E and A. both urea and OxLDL were found significantly as- sociated to CRP levels > 0. time.01 0.11 0. for the first tors and related vitamins.04 0. two groups (Figure 2).001 0. Nontraditional cardiovascular risk fac. pro- tein intake and albumin levels are reported. patients on VSD showed sig- nificantly lower levels of tHcy.20 0. only urea re- sulted significantly correlated to CRP levels (Table 4). r –0.11 – 0.001 NS NS NS NS . Patients on CD exhibited a positive corre- lation between CRP and urea (p < 0.14 0.20 0.56 0. tients showed a mild but significant reduction No significant differences of antibody of LDL oxidation with lower TBARS con. In Table 3.12 low-protein diet p 0. Figure 4 shows the different relationship between OxLDL and LDL-C. Discussion Our results point out to an overall benefi- cial effect of vegan diet on traditional and Figure 3. Patients on CD showed a significant correlation between OxLDL and lipids or apolipoproteins (TC. Table 2.09 supplemented diet p NS NS NS NS NS NS NS NS NS NS Conventional r 0.002 NS 0. vegan pa.22 – 0. Lp(a) and CRP together with significantly increased concentrations of vitamin B12 and folic acid (Figure 3).18 0.05) (Fig- ure 5) and an inverse correlation between Lp(a) and albumin both absent in vegan pa- Figure 2. LDL-C HDL-C TC TG A1 B A/B TBARS VIT E OxLDL-Ab Vegan. titers against OxLDL were found between the centrations.003 NS 0. Nontraditional cardiovascular risk factors tients. a reduction of CRP levels. In addition. vegan patients did not dis- 1). LDL-C and Apo B) which was not ob- served in vegan group (Table 2).08 – 0. Spearman rank correlation analysis between OxLDL and oxidative stress and traditional cardiovascular risk factors. Cardiovascular risk factors in patients with end-stage renal disease 107 showed an increased apoA1/B ratio (Figure In spite of that. A multiple linear regression model for CRP levels was employed in the overall popu- lation of patients.11 0. Among non-traditional CVRF. TG.06 – 0. At the multivariate analysis. non-traditional CVRF including.

002 [Bergesio et al. Urea. Monzani.001 The lower concentrations of OxLDLAb (g/day) (15 – 37) (31 – 66) Albumin 3 547 3 937 < 0. By (mg/dl) (11 – 800) (35 – 840) contrast. 2001. Shoij and coworkers [2000] have re- cently suggested a possible anti-atherogenic role of OxLDLAb by maintaining a low plasma concentration of OxLDL.7) (0 – 1. Protein intake (Pi). Spearman rank correlation analysis between OxLDL and ApoB and LDL-C. as suggested by Urea 74 103 < 0. Spearman rank correlation analysis between Urea and CRP.05 titre found in vegan patients could reflect the (mg/dl) (2 364 – 4 751) (2 797 – 5 636) reduced LDL oxidation and are in keeping CRP 0.05 with previous reports indicating OxLDLAb (mg/dl) (0 – 0.001 the failure of a correlation between lipids and (mg/dl) (40 – 150) (56 – 147) LDL oxidation.5 < 0. 1994]. Lp(a) and albumin in patients on only a reduced lipid peroxidation. Guasparini et al. VSD patients showed not Table 3. Maggi et al.5 42.7) as a marker of the atherosclerotic process Lp(a) 124 222 < 0. CRP. Pi 26. Bergesio. but also a reduced lipid susceptibility to oxidation. denced by the significant reduction of OxLDL VSD CLPD p and TBARS levels. Recently.4 < 0.2 0. a . In particular. Figure 5. as evi- vegan-supplemented (VSD) and conventional low-protein (CD) diet. 108 Figure 4.

In dialysis patients.074 0. plained by the different vitamins A and E sta. with a decrease of lipid peroxidation of both On the other hand VSD is deficient of vitamin plasma [Krajcovicova-Kudlackova et al. they are believed to exert their major mecha- 1992] may contribute to such a reduction. pendently associated with lower cardiovascu.Cardiovascular risk factors in patients with end-stage renal disease 109 Table 4. Zim- 1991] as well as in uremia [Cressman et al.91 – 1. re- a-ketoacids which could scavenge hydrogen duced tHcy and Lp(a) levels. 2002. When this branes [Peuchant et al. . many studies have been published Lp(a) and tHcy. Indeed vegan diet is rich in fo- Several studies have reported an antioxidant lic acid which. through which creased catalase activity [Pronczuk et al. during their oxidative process. as we used to do in our patients. activity [Bonnefort-Rousselot et al. 1999. both regarded as non-tra. 1999]. Genest et al. observed in vegan patients. 2000]. 1999]. mermann et al. by the significantly higher concentrations of Further investigations are needed to as. the lower tHcy levels found lar mortality in patients with end-stage renal in our patients on VSD could be explained disease (ESRD). tHcy levels In our study the reduced lipid peroxida. like vitamin E. 1999. increased HDL-C peroxide thus reducing lipid peroxidation.001 Lp(a) –0. it is possible that a oxide anion radical and hydrogen peroxide higher vitamin C content as well as an in.019 – 1. ditional factors which may affect cardiovas. predialysis and dialysis patients [Stenvinkel transferase recognised to have an antioxidant et al.012 – 1. as similar serum levels were detected in duce. Most important. r value p value OR CI 95% p Pi (Maroni) 0. Mezzano et tion observed in vegan patients cannot be ex.3 mg/dl (n = 60).96 0. To date. A and in particular of a-tocopherol and indirect mechanism [Bayes et al. as and folic acid concentrations together with a reported by Nath and coworkers [1994] and direct antioxidant activity of a-ketoacids may observed on RBC membranes by Peuchant all contribute to the reduced LDL oxidation and coworkers [1997]. 1998. malnutrition and atherosclerosis in uremia cular morbidity and mortality in the general [Arici and Walls 2001. recently regarded as a strong several enzymes especially paraoxonase. Moustapha et al. B12 and B6 unless it is regularly supplemented Pronczuk et al. 1997].006 OxLDL 0. these patients. al. be markedly reduced in vegan patients.52 < 0. vitamin B12 and possibly vitamin certain the actual role of OxLDL and B6 (not investigated in our study) present in OxLDLAb in the atherogenic process.001 Gender 0. patients on vegan diet nally be influenced also by the higher HDL-C showed a moderate but significant reduction levels linked. 1995. are increased [Bissoli et al. CRP > 0. 2001]. Zimmermann et al. 1992] and red blood cell mem. generation [Loscalzo 1996]. Bergstrom and Lind- population [Boushey et al. to the presence of of CRP levels. vascular disease. Stenvinkel et al.1 – 3. Multivariate analysis on relative risk of different risk factors on CRP (n = 60). 1999]. supplementation is not provided. Multiple linear regression analysis of Table 5. folic acid.02 NS Urea 0.077 0. 1998]. nism for development of atherosclerotic Another possible mechanism could be di. rectly linked to the antioxidative action of Besides the possible role of vitamin C.02 NS OxLDL 1. However. 1992. were found to strated OxLDLAb titre to be a factor inde.046 1.17 NS prospective observational study demon. 1995. on the relationship between inflammation. would afford effect of vegan diet due to its higher content of antioxidant protection through a both direct vitamins C. In particular. PAF and independent predictor for CVD in both acetylhydrolase and lecithin-cholesterol acyl.044 1.09 NS Age 0.66 0.9 NS tHcy 0. super- both groups. at least in part. strom 1998. Both Lp(a) and tHcy are reported to in- tus.08 NS Urea 1. The inhibition of LDL oxidation could fi.

could be responsible affecting CRP concentrations in our study. the positive correlation urea and/or uremic toxins and the acute-phase reported in recent investigations between proteins in ESRD. 110 Zimmerman and coworkers reported that the for increased CRP levels. the reduced albumin con. above indeed those currently observed in our On the other hand. . urea would not likely play a role by well as for the increased concentrations of itself. inflammation may cause increased tional status and/or inflammatory condi. Pereira et al. little if no evidence at all exists The great difference in urea levels found concerning the role of urea as a possible me- between the two groups may well represent a diator of the acute-phase response with sub- possible explanation. might induce macrophage exclusively in patients on CD. 2004]. Urea in fact was the sequent increased oxidative stress and devel- only factor to show a significant relative risk opment of lipoprotein abnormalities. including LDL. higher than patients on vegan diet. 1999]. fested by normal C reactive protein level. Accumulation of advanced glycation is even more interesting if we think that albu. we suggest that the dif. which ac- observed in chronic renal failure. end products (AGEs) in plasma and vas- min levels of vegan patients are significantly culature of uremic patients is another possible lower than those observed in patients on CD. IL-6. or Moreover. both conditions on dialysis treatment [Stenvinkel et al. 1999. proliferation and inhibition of inducible nitric Indeed. mechanism through which the uremic state As a matter of fact. although the biochemical path- ferences observed in CRP and Lp(a) levels ways through which malnutrition. al. 1998]. tained uremic solutes. been associated to increased cardiovascular SAA and fibrinogen [Loscalzo 1996] found mortality in dialysis patients [Bergstrom and in uremic patients either on conservative or Lindholm 1998]. it is unlikely that latent patients as well as in most patients on protein inflammatory conditions may have occurred restriction diets. To date. more likely. them. but rather as a biomarker of other re- Lp(a). ment of atherosclerotic lesions [Moeslinger et ent differences could be elicited between al. Moeslinger et al. no direct data have been reported zymes activity [Zimmermann et al. as it is mani. Stenvinkel et al. often. like the re. urea levels in uremic patients are well-known tions. reported that to a real malnutrition as indicated by stable elevated urea concentrations in vitro. phase response which actually would be the In the presence of increased concentrations crucial factor for the development of CVD. for the decrease of serum albumin levels as However. which can be taken up by patients on conventional diet showed both scavenger receptors on monocytes and trig- Lp(a) and CRP concentrations significantly ger the atherosclerotic process [Horkko et al. To date. The result 1992]. also known as “uremic malities of lipoprotein metabolism commonly toxins” like guanidines and others. 2001]. elevated urea levels would acute-phase inflammatory response and reflect an overall increase of protein catabolic biomarkers of oxidant stress [Himmelfarb et products capable to maintain/activate an un- al. are often associated to an activated acute. 1994]. Multivariate linear presence of an inflammatory condition. derlying chronic inflammatory process as Malnutrition and hypoalbuminemia have demonstrated by the accumulation of CRP. many molecules can be carbamylated Despite their normal serum albumin levels.Bergesio. including the general reduction of lipolytic en. However. well clinical and biochemical parameters. Monzani. tually would be involved in inflammation and duced concentrations of HDL-C and Apo A1 atherogenesis [Glorieux et al. TNF-a] [Schwedler et evident inflammatory condition. indi. 2002. and more are likely to occur independently from nutri. of urea. [Mitch 2002]. or pathophysiologic link existing between the as a direct toxin. about a possible causal relationship between At the same time. Irrespectively of whether CRP and TBARS and OxLDL confirmed the they act either as a surrogate. leads to the production of proinflammatory centrations cannot be ascribed either to any cytokines (IL-1. Consequently. Guasparini et al. 1999]. regression analysis further confirmed and cated by an elevated CRP and serum amyloid strengthened the role of urea as a major factor A (SAA) concentration. fibrinogen and even for many abnor. both groups were just selected to oxide synthesis thus contributing to develop- be in a good metabolic control and no appar.

Tosi P 2001 Autoantibodies against oxi. Varghese Z. Frattoni A. lipids. Lindholm B 1998 Malnutrition. Stenvinkel P. Mandragona R. Cirami C. Paganini EP. Kid- may prevent and/or downregulate the devel. Sarnak MJ 1998 Cardiovascular diets in preventing the development of car. Legrand A. Ikizler TA. Nephron 42: 196-199 favorable profile of traditional and non-tra.Cardiovascular risk factors in patients with end-stage renal disease 111 It is noteworthy that just moderately ele. An Salvadori M. ney Int 65: 2184-2192 cular. Kervinen K. Peynet J. likely the consequence of an overall reduced Esterbauer H. Romero R 2001 and apolipoproteins after a three-week vegetarian diet. Klein W 1994 Autoantibodies to oxi- activation of the acute-phase proteins sec. De Deyn PP. teristics during macrophage foam cell formation. Bonal J. Clin tients on CD. Schumacher M. Nai M. Genest J Jr. as those found in our pa- proteins (HDL) and the oxidative hypothesis. 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