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Published ahead of print on January 7, 2009
Clin J Am Soc Nephrol 4: 142-151, 2009
© 2009 American Society of Nephrology
doi: 10.2215/CJN.02280508
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Dialysis

Assessment of Myeloperoxidase and Oxidative {alpha}1-Antitrypsin in Patients on Hemodialysis

Hirokazu Honda*, Masashi Ueda{dagger}, Shiho Kojima{dagger}, Shinichi Mashiba{dagger}, Yuki Hirai*, Nozomu Hosaka*, Hiroki Suzuki*, Masanori Mukai*, Makoto Watanabe*, Keiko Takahashi{ddagger}, Kanji Shishido{ddagger}, and Tadao Akizawa*

* Division of Nephrology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan; {dagger} Ikagaku Co. Ltd., Kyoto, Japan; {ddagger} Kawasaki Clinic, Kawasaki, Japan

Correspondence: Dr. Hirokazu Honda, Division of Nephrology, Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan. Phone: +81-3-3784-8533; Fax: +81-3-3784-5934; E-mail: hondah{at}med.showa-u.ac.jp


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Disclosures
 References
 
Background and objectives: The present study assesses the effects of the oxidative stress marker, myeloperoxidase (MPO), and the possible MPO-related oxidative stress marker, oxidative {alpha}1-antitrypsin (oxAT), on carotid intima-media thickness (CIMT) and protein-energy wasting (PEW) in patients on hemodialysis (HD).

Design, setting, participants, & measurements: Blood samples were obtained from 383 patients before HD to measure WBC count, serum albumin, lipids, high-sensitivity C-reactive protein (CRP), {alpha}1-antitrypsin (AT), interleukin-6, oxidative LDL-C, MPO, and oxAT. We assessed both CIMT and the geriatric nutritional risk index (GNRI) in this cross-sectional competitive study.

Results: Levels of MPO and oxAT correlated. Myeloperoxidase was associated with max-CIMT, and oxAT correlated with max-CIMT and GNRI. Multivariate linear regression models showed that MPO and oxAT were independent predictors of increasing max-CIMT, whereas oxAT, but not MPO, independently correlated with GNRI. In four combined MPO and oxAT groups classified according to median values, a multinomial logistic regression model showed that high MPO together with high oxAT was independently associated with increased max-CIMT. Moreover, the OR for max-CIMT with positive PEW and high MPO was significantly increased in the four groups with combined MPO and PEW.

Conclusions: High MPO with high oxAT and high MPO with PEW seem to contribute to plaque formation in patients on HD, whereas elevated MPO or oxAT alone might not predict increasing CIMT. In contrast, a high oxAT value seems to be an independent predictor of PEW in patients on HD.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Disclosures
 References
 
Ahigh prevalence of cardiovascular disease (CVD) events and of protein-energy wasting (PEW) is significantly associated with increased mortality and morbidity among patients undergoing hemodialysis (HD) (1). The progression of atherosclerosis and PEW in such patients is accelerated by various factors, in particular oxidative stress and inflammation. Oxidative stress is closely associated with advancing atherosclerosis (2) and is a principal risk factor for cardiovascular mortality in patients on HD (3). Such patients develop uremic syndrome per se or factors associated with uremia and an excessively inflamed state with marked hypoalbuminemia (4). Increased oxidative stress and higher levels of C-reactive protein (CRP) and pro-inflammatory cytokines contribute to increased protein catabolism in these states.

Myeloperoxidase (MPO) is a hemoprotein that is secreted during the activation of neutrophils and of reactive species-generating enzyme, which acts in host defense by catalyzing the production of hypochloric acid (HOCl) (5). Neutrophil-derived MPO induces vascular injury responses such as endothelial dysfunction and thus MPO might play an important role in vascular injury and atherogenesis (6). Elevated levels of MPO are associated with coronary heart disease and predict risk in patients with acute coronary syndromes (7,8). Myeloperoxidase influences atherosclerosis not only in nonuremic patients, but also in patients with end-stage renal disease (ESRD), especially when under HD therapy. During HD sessions, MPO might be released in association with biocompatibility factors such as deleterious effects induced in the blood during dialysis (9). A high MPO value, as well as hepatic acute phase proteins and increased expression of pro-inflammatory interleukins, is associated with CVD among patients on HD (10), and increased levels of MPO are closely linked to mortality in such patients (11). Moreover, MPO influences PEW in patients on HD (12).

However, MPO levels are not associated with atherosclerosis progression in nonuremic patients (13), which suggests that serum MPO levels do not always reflect MPO catalysis of HOCl.

Free radicals released from activated neutrophils oxidize the 52-kD acute-phase protein {alpha}1-antitrypsin, which is a typical serine proteinase inhibitor (14). Thus, oxidized {alpha}1-antitrypsin (oxAT) is a potential marker of activated neutrophil-associated oxidation including MPO catalyzing HOCl production (15).

The present competitive study was designed to estimate MPO and oxAT values to predict carotid intima-media thickness (CIMT) and PEW in patients on HD.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Disclosures
 References
 
Patients
The cohort of patients (n = 383; males 61%; age 63 ± 13 yr) enrolled in this cross-sectional study were all on HD. Patients with clinical signs of overt infection, acute vasculitis, or liver disease at the time of recruitment were excluded. The background of each patient including cause of ESRD, diabetes mellitus, BP, and cardiovascular disease was recorded.

The causes of ESRD were chronic glomerulonephritis (29%), diabetic nephropathy (33%), nephrosclerosis (13%), polycystic kidney disease (8%), other diseases (7%), and unknown (10%). All recruited patients were essentially treated with three sessions of routine conventional bicarbonate HD each week (3 to 4 h per session) using standard high-flux cellulose acetate (CA), polysulfone (PS) or other dialysis membranes. The dialysis dosage was estimated by second-generation Kt/V using the Daugirdas formula (16). Patients were recommended to maintain a daily protein intake of >1.0 to 1.2 g/kg body weight. The dietary protein intake circulated by the normalized protein catabolic rate (nPCR) was estimated (17).

Venous blood samples were withdrawn before the next HD session on day 3 after the previous session to analyze routine biochemical parameters and lipids, high-sensitivity CRP (hsCRP), oxidized LDL-cholesterol, (oxLDL-C), and oxAT and were stored at –70°C before measuring IL (IL)-6 and MPO.

The Ethics Committee of Showa University School of Medicine, Tokyo, Japan, approved the study protocol and written informed consent was obtained from all participating patients.

Carotid Ultrasound
The patients were examined using B-mode ultrasound scanning equipped with a 14-MHz linear probe. The investigative protocol involved an examination of the carotid artery in both transverse and longitudinal planes and CIMT was measured on the far wall of the common carotid artery 2 to 4 cm proximally to the bifurcation. Intima-media thickness was defined as the distance between the leading edges of the lumen interface and the media-adventitia interface of the far wall. Both carotid arteries were examined and the maximal CIMT values were additionally analyzed. The interobserver technical error of measurement was 5.5%.

Geriatric Nutritional Risk Index (GNRI)
The GNRI was calculated from the serum albumin value and dry body weight (BW) using the following formula: GNRI = [1.489 + Alb (g/L)] + [41.7xBW/ideal BW] (18,19). The ideal BW was calculated from height and a body mass index (BMI) of 22.

Biochemical Methods
Both hsCRP and {alpha}1-antitrypsin were measured by immunonephelometry. Creatinine (Cr), urea, and s-Alb (bromocresol purple) were determined by routine procedures and HDL-C was analyzed after lipoprotein containing ApoB was precipitated using phosphotungstic acid. Levels of LDL-C were determined by immunonephelometry and those of oxLDL-C were measured using an enzyme-linked immunosorbent assay (ELISA) with sensitivity of 1 mU/L, an intra-assay coefficient of variation (intraCV) of 2.5%, and an interassay coefficient of variation (interCV) of <9.0% (Oxidized LDL ELISA Kit; Mercodia, Uppsala, Sweden). Levels of IL-6 were measured using an ELISA with sensitivity of 0.16 pg/ml, an intraCV of 4.8%, and an interCV of <7.8% (QuantiGlo Human IL-6 ELISA Kit; R&D Systems Inc., Minneapolis, MN, USA). Serum MPO levels were measured using an ELISA kit with sensitivity of 0.35 ng/ml, an intraCV of 3.4%, and an interCV of <5.5% (MPO ELISA Kit, Immundiagnostik AG, Bensheim, Germany). Oxidative AT was analyzed using an ELISA with a monoclonal antibody against oxidized {alpha}1-AT in which chloramine T-oxidized {alpha}1-AT was the antigen (15). The sensitivity of oxAT measurement was 1.0 ng/ml with an interCV of <6.7%.

Statistical Analyses
Data are presented as means ± SD or median (range) unless otherwise noted, with P < 0.05 taken to indicate statistical significance. Normally distributed variables were compared between two groups using t test, whereas the Wilcoxon rank-sum test was used for non-normal distributed variables. Comparisons among three groups were analyzed by ANOVA with a post hoc Tukey–Kramer test when differences were statistically significant. Nominal variables were compared between two groups using Fisher’s exact test and for more than two groups using the {chi}2 test. Correlations were calculated using the Spearman rank test ({rho}) and those in normal distributed variables were calculated using Pearson’s correlation test (r). Independent associations between one dependent variable and more than two independent variables were assessed using multiple linear and logistic regression analysis. Data were analyzed using the statistical software, JMP ver. 7 (SAS Institute Inc., Cary, NC, USA) and NCSS 2004 and PASS 2005 (Number Cruncher Statistical Systems, Keysville, UT, USA).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Disclosures
 References
 
Associations of MPO and oxAT with Laboratory Data
Median levels of MPO and oxAT were 58.6 ng/ml (range 8.0 to 436.0) and 39.1 ng/ml (range 10.1 to 876.3), respectively, and the correlation between (log) MPO and (log) oxAT was significant (r = 0.25; P < 0.0001, Figure 1). Multivariate models showed that MPO correlated with gender, Kt/V, WBC, and oxAT (Table 1), whereas oxAT correlated with gender, BMI, hsCRP, and MPO (Table 2). Oxidative AT did not correlate with {alpha}1-antitrypsin ({rho}, 0.04; P = 0.360).


Figure 1
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  		Figure 1. Correlation between log myeloperoxidase (MPO) and log oxidative {alpha}1-antitrypsin (oxAT).

 

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  		Table 1. Factors contributing to myeloperoxidase levels

 

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  		Table 2. Factors contributing to oxidative {alpha}1-antitrypsin values

 
Characteristics and Laboratory Data from Patients Classified According to Median MPO or oxAT Values
Patients were divided based on their median percentile MPO and oxAT values. The prevalence of DM was low and WBC counts, as well as hsCRP and oxAT levels, were higher in patients with a high MPO than a low MPO value (Table 3). However, patients with high oxAT values were older, comprised fewer males, smoked less, and had lower BMI values than those with low oxAT (Table 4).


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  		Table 3. Laboratory data for patients grouped according to median percentile of myeloperoxidase

 

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  		Table 4. Laboratory data for patients grouped according to median percentile of oxidative {alpha}1-antitrypsin

 
The max-CIMT value was increased in both the high MPO and high oxAT groups (Figure 2) and GNRI was decreased in the high oxAT group, but did not differ between the MPO groups (Figure 3).


Figure 2
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  		Figure 2. Levels of carotid intima-media thickness (CIMT) according to median values of myeloperoxidase (MPO) and oxidative {alpha}1-antitrypsin (oxAT).

 

Figure 3
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  		Figure 3. Levels of geriatric nutritional risk index (GNRI) according to median values of myeloperoxidase (MPO) and oxidative {alpha}1-antitrypsin (oxAT).

 
Contributions of MPO and oxAT to Increased max-CIMT and GNRI
Both MPO and oxAT were independently associated with increased max-CIMT in the multivariate model including age, gender, HDL-C, and DM as independent factors (Table 5). Oxidative AT independently contributed to a decrease in GNRI in the multivariate model including age, gender, DM, and log hsCRP (Table 6, model 1) or age, gender, DM, and Alb (Table 6, model 2), but not MPO.


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  		Table 5. Factors contributing to max-CIMT

 

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  		Table 6. Factors contributing to geriatric nutritional risk index

 
Levels of MPO and oxAT Compared with max-CIMT and GNRI
Max-CIMT (1.41 ± 0.67 mm) was significantly increased in the group with high MPO and high oxAT compared with the other groups (high MPO with low oxAT, 1.12 ± 0.30 mm; low MPO with high oxAT, 1.08 ± 0.34; low MPO with low oxAT, 1.09 ± 0.33 mm) (Figure 4). The high MPO and high oxAT group had more inflammation (hsCRP 0.61 ± 1.63 mg/dl) than the other groups (high MPO with low oxAT, 0.23 ± 0.35 mg/dl; low MPO with high oxAT, 0.25 ± 0.52 mg/dl; low MPO with low oxAT, 0.18 ± 0.31 mg/dl; Figure 4).


Figure 4
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  		Figure 4. Elevated levels of both myeloperoxidase (MPO) and oxidative {alpha}1-antitrypsin (oxAT) are associated with high high-sensitivity C-reactive protein (hsCRP) and increasing carotid intima-media thickness (CIMT), whereas elevated oxAT alone contributes to decrease in geriatric nutritional risk index.

 
The GNRI (96.0 ± 7.7) was decreased in the group with high MPO and high oxAT, but similar to that (95.9 ± 7.1) in the group with low MPO with high oxAT (Figure 4). The GNRI in the group with high MPO and low oxAT was significantly greater than that in the groups with high MPO and high oxAT, or low MPO and high oxAT.

Impact of MPO and oxAT with PEW on Increased max-CIMT and hsCRP
The influence of high MPO and high oxAT in patients with PEW on CIMT and hsCRP was assessed by combining patients according to MPO or oxAT median values, and PEW defined as less than median GNRI value. The max-CIMT was higher in the group with high MPO with PEW than with low MPO without PEW. However, max-CIMT values between high MPO with and without PEW did not differ (Figure 5a). The hsCRP levels between high MPO with and without PEW also did not differ, although they were more increased in the group with high MPO without PEW than in that with low MPO without PEW (Figure 5b).


Figure 5
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  		Figure 5. Associations between elevated levels of myeloperoxidase (MPO) and oxidative {alpha}1-antitrypsin (oxAT) with protein-energy wasting (PEW) defined as geriatric nutritional risk index (GNRI) < 97 for increasing max carotid intima-media thickness (CIMT) and high-sensitivity C-reactive protein (hsCRP). Patients were assigned to groups according to median values of MPO and oxAT in Tables 1 and 2 as follows: high MPO and high oxAT (n = 122), high MPO and low oxAT (n = 70), low MPO and high MPO (n = 69), low MPO and low oxAT (n = 122). Patients were assigned to groups according to median values of MPO and PEW as yes or no as follows: high MPO and PEW yes (n = 90), high MPO and PEW no (n = 98), low MPO and PEW yes (n = 97), low MPO and PEW no (n = 92). *, P < 0.05; **, P < 0.01; ns, not significant.

 
Among the groups combined according to oxAT and PEW, the tendency for max-CIMT and hsCRP levels to increase was similar to that in the group with combined MPO and PEW (Figure 5, c and d).

Powerful Predictive Value of both High MPO and oxAT, and High MPO with PEW for Increased max-CIMT
We estimated the predictive value of combining the groups with MPO and oxAT, with MPO and PEW, and with oxAT and PEW for max-CIMT using multinomial analysis. The parameters included age, gender, DM, CVD, Alb, HDL-C, hsCRP, and the groups with combined MPO and oxAT or with combined MPO and PEW (Figure 6), or with combined oxAT and PEW as independent factors. Protein-energy wasting was estimated as being above or below the median GNRI percentile. In the model groups combined according to MPO and oxAT being above or below the median percentile, the odds ratio (OR) of the group with high MPO and high oxAT (OR, 2.28; 95% CI 1.15 to 4.69) was significantly higher than that of the other MPO and oxAT combinations (Figure 6a).


Figure 6
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  		Figure 6. Odds ratios of significant predictors for max-carotid intima-media thickness (CIMT) (>1.1 mm versus ≤1.1 mm). Model includes age (>64 versus ≤64 yr), gender (male versus female), diabetes mellitus (DM) (yes versus no), cardiovascular disease (yes versus no), albumin (>3.7 versus ≤3.7 g/dl), HDL-C (>45 versus ≤45 mg/dl), high-sensitivity C-reactive protein (hs-CRP) (>0.2 versus ≤0.2 pg/ml), and groups with combined myeloperoxidase (MPO) and oxidative {alpha}1-antitrypsin (oxAT) (Figure 5a), or with combined MPO and protein-energy wasting (PEW) as independent factors (Figure 5b). Patients were assigned to groups according to median values of MPO and oxAT as follows: high MPO and high oxAT (n = 122), high MPO and low oxAT (n = 70), low MPO and high MPO (n = 69), low MPO and low oxAT (n = 122). Patients were assigned to groups according to median values of MPO and PEW yes or no as follows: high MPO and PEW yes (n = 90), high MPO and PEW no (n = 98), low MPO and PEW yes (n = 97), low MPO and PEW no (n = 92).

 
In the model groups combined according to MPO value and PEW, the OR of that with high MPO and PEW (OR, 2.49; 95% CI 1.12 to 5.57) was significantly increased (Figure 6b). A high oxAT value together with PEW tended to associate with increasing max-CIMT but the values did not reach statistical significance (P = 0.15).


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Disclosures
 References
 
This study demonstrated the predictive value of MPO and oxAT for increasing CIMT since high MPO and high oxAT values were independently associated with max-CIMT (Table 5). The max-CIMT levels were significantly increased in patients with increases in both MPO and oxAT (Figure 4), and the odds ratios of the group with both high MPO and high oxAT were significantly increased compared with an elevation in either alone (Figure 6a).

Oxidative AT might reflect activated neutrophil-derived enzymatic oxidation and the inflamed state induced by oxidative stress, because oxAT correlated with MPO (Figure 1) and tended to associate with hsCRP ({rho}, 0.10; P = 0.052). Myeloperoxidase is an important marker of oxidative stress during HD sessions (9,20) and is associated with chronic mild inflammation (21). Interestingly, serum MPO as well as oxAT correlated with female gender in multivariate models in the present study (Tables 1 and 2), whereas another study has not found a significant association between MPO and gender in patients under HD (11). A small cohort and the single measurements of oxidative stress markers might have affect these findings and gender differentiation could theoretically enhance MPO levels in patients under HD. For instance, estrogen can cause MPO release from neutrophils (22,23) and induce peroxidase-mediated oxidation (22). Whereas serum estradiol levels in patients under HD remain controversial (24), those in female patients under HD might be higher than in age-matched females with normal kidney function (25). Therefore, female gender might be partially responsible for high MPO and oxAT levels in patients under HD.

However, our findings suggest that increased MPO levels do not always reflect inflammation, and might be a consequence of accumulation. High hsCRP levels are associated with CVD and have been linked to inflammatory states including leukocyte-derived MPO. We found here that hsCRP levels were not increased in patients with high MPO together with low oxAT (Figure 4). The elevation of MPO alone might indicate less clustering of factors contributing to increased CIMT, such as those associated with endothelial cell adhesion in mechanisms in which inflammation could injure the vascular endothelium (10). Therefore, MPO might be a marker of inflammation, but is not a pure, independent predictor for atherosclerosis in HD patients.

However, elevated oxAT alone did not seem to be a powerful predictor of increased CIMT, as it is also increased in patients with inflammatory diseases. Levels of CRP and oxAT in patients with rheumatoid arthritis are significantly higher than those in normal individuals (15). Not only MPO, but also other agents oxidize AT, since peroxide lipid can oxidize methionine residues of AT (26). Measurements of oxAT in the present study included oxidized methionine residues, suggesting a highly oxidative state. However, levels of hsCRP in patients with both low MPO and high oxAT were significantly decreased compared with those with both high MPO and high oxAT (Figure 4). Oxidative stress is closely associated with the development of atherosclerosis (27). Why elevated oxAT alone did not predict an increase in CIMT was unclear, but the findings might be partially influenced by the accumulation of less cleansed oxAT because its higher molecular weight (>52 kD) would prevent passage through the dialysis membrane (15).

The present study found that oxAT was associated with a decrease in GNRI (Figure 3) and that GNRI was decreased not only in patients with both high MPO and high oxAT, but also in those with only elevated oxAT (Figure 4). Moreover, oxAT, but not MPO, was an independent predictor of PEW (Table 6). The GNRI is a more reliable risk index of nutritional state in patients on HD (18) than either the malnutrition-inflammation score (28) or subjective global assessment (29,30). However, the reliability of GNRI to predict PEW has been assessed in patients on HD (18) of a similar age to ours. Thus, oxAT might be a better predictor than MPO to estimate nutritional status among patients on HD. Both MPO and oxAT were associated with inflammation (increased hsCRP levels), suggesting that MPO is involved in protein catabolism as well as oxAT. We speculated upon why oxAT contributed more than MPO to a decrease in GNRI in patients on HD.

The GNRI formula is based on serum Alb (19). Thus, the PEW estimated by GNRI might depend on factors composing the formula. In the present study, serum levels of oxAT tended to inversely correlate with Alb ({rho}, –0.10; P = 0.050) and levels were higher in older patients (Table 4). In contrast, MPO did not correlate with age ({rho}, 0.03; P = 0.56) and Alb ({rho}, –0.01; P = 0.89). Another group has also described the absence of a significant association between MPO and Alb in patients on HD (11). Taken together, these findings and ours suggest that oxAT plays a specific role in nutritional status.

Levels of {alpha}1-antitrypsin functioning as a serine proteinase inhibitor are usually increased in patients on HD because of the accumulation of {alpha}1-antitrypsin with a higher molecular weight. In contrast, {alpha}1-antitrypsin is closely linked to inflammation and it is inversely associated with Alb in patients on HD (31). The present study found high {alpha}1-antitrypsin levels in patients with inflammatory conditions; that is, close correlations with IL-6 ({rho}, 0.50; P < 0.0001) and hsCRP ({rho}, 0.39; P < 0.0001) and a correlation with a decrease in Alb ({rho}, –0.17; P = 0.0008). From another perspective, protease levels increase and are involved in protein catabolism as well as in disturbed carbohydrate metabolism in patients on HD (32). Thus, {alpha}1-antitrypsin might be oxidized, resulting in a loss of {alpha}1-antitrypsin activity and diminished capacity to inhibit serine protease (33). We found that the ratio of oxAT/{alpha}1-antitrypsin inversely correlated with GNRI ({rho}, –0.17; P = 0.001), indicating that increased oxAT levels accordingly enhance catabolism in patients on HD. Moreover, oxAT might activate monocytes, which in turn activate NADPH oxidase, finally producing chemokines and cytokines (34). If so, then oxAT not only produces, but also plays roles in enhancing or modifying inflammatory reactions. Therefore, oxAT would contribute to PEW in patients on HD.

Protein-energy wasting yields high mortality and influences the advance of atherosclerosis in patients on HD, and CVD is a pivotal risk factor for mortality in such patients (1). Hence, the overall estimation of CVD and PEW in patients on HD might benefit from measuring markers associated with inflammation and oxidative stress. When focusing on increasing CIMT that is a surrogate marker for CVD, GNRI as a precise marker of PEW in patients on HD was not a predictor ({rho}, –0.06; P = 0.183). However, the predictive value of GNRI for increasing CIMT was increased when analyzed using the multivariate model in patients grouped according to the median MPO value; the predictive value of high MPO with PEW (defined as <GNRI median value) significantly increased (Figure 6b). The OR of high oxAT with PEW increased, but did not reach statistical significance. These results might depend on the fact that we used the median GNRI value of 97.0 as the cutoff, whereas others have used different values. Yamada et al. used 91.2 (18) and Bouillanne et al. used 98.0 (19). When we defined PEW as a lower GNRI value of 91.2, the OR for increasing CIMT was significantly increased in the group with high oxAT together with PEW (data not shown). Thus, both MPO and oxAT values together might provide a more suitable estimation of CVD-related and/or PEW-associated morbidity and mortality in patients on HD.

However, the results of our study must be considered with the following caveats. First, the number of patients was limited and the cross-sectional nature of the study design prevented us from reaching any mechanistic conclusions. Second, the single point measurement of biomarkers for oxidative stress and inflammation does not permit accurate evaluation (35). Third, we could not identify an association between oxAT and PEW estimated by non-GNRI means and by a quantitative assessment of advanced atherosclerosis. Thus, a large prospective cohort study is required to clarify the reliability of oxAT values in predicting atherosclerosis and PEW in patients on HD.

Conclusion
In conclusion, oxAT and MPO seem to be useful markers with which to estimate increasing CIMT. Furthermore, oxAT might be an independent predictor of PEW in patients on HD.


   Disclosures
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Disclosures
References
 
None.


   Acknowledgments
 
The authors thank Naoko Nishiyama for excellent technical assistance.

H.H. is funded to conduct this study from the Kidney Foundation, Japan (Grant No. JKF 06-1).


   Footnotes
 
Published online ahead of print. Publication date available at www.cjasn.org.

Received May 9, 2008. Accepted September 12, 2008.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Disclosures
 References
 

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