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NDT Advance Access originally published online on April 28, 2008
Nephrology Dialysis Transplantation 2008 23(10):3295-3301; doi:10.1093/ndt/gfn221
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Relationship between dialysate oxidized protein and peritoneal membrane transport properties in patients on peritoneal dialysis

Sheron Latcha1,2, Susana Hong2, Nora Gibbons2, Nina Kohn3 and Joseph Mattana1,2,3

1 Department of Medicine, North Shore University Hospital, Manhasset 2 Long Island Jewish Medical Center, New Hyde Park 3 The Feinstein Institute for Medical Research, Manhasset, NY, USA

Joseph Mattana, Division of Kidney Diseases and Hypertension, Long Island Jewish Medical Center, 100 Community Drive, 2nd Floor, Great Neck, NY 11021, USA. Tel: +1-516-465-3010; Fax: +1-516-465-3011; Email: mattana{at}lij.edu



   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. Increased levels of oxidized proteins have been reported in the serum of patients with end-stage renal disease, though little is known regarding the oxidized protein content of the dialysate in patients on peritoneal dialysis (PD) and no information is available as to how this may correlate with important clinical and laboratory variables, including abnormal peritoneal membrane function. In this study we attempted to identify oxidized proteins in the dialysate of patients on PD using western blot analysis, and examined the relationship between these proteins and the function of the peritoneal membrane and other clinical and laboratory variables.

Methods. Peritoneal dialysate and serum samples were obtained from 18 patients on PD, and western blot analysis using an antibody to oxidized protein was carried out with reprobing for albumin. Oxidized protein/albumin ratios were determined and compared with various clinical and laboratory variables including peritoneal equilibration test results.

Results. Oxidized protein/albumin ratios were higher in the dialysate of patients who were high/high average transporters compared to low/low average transporters. Oxidized protein ratios were also found to be higher in the dialysate of patients who had diminished urine output as a reflection of loss of residual renal function. Negative correlations were noted between oxidized protein ratios in the dialysate and serum albumin levels and creatinine clearance.

Conclusions. Higher levels of oxidized protein in the dialysate appear to be correlated with high/high average peritoneal membrane transport characteristics and may be related to loss of residual renal function. These preliminary findings suggest that it is plausible that oxidized proteins in the dialysate might play a contributory role in complications including membrane damage and ultrafiltration failure in patients on PD.

Keywords: membrane transport; peritoneal dialysis; protein oxidation



   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
Patients with end-stage renal disease suffer from enhanced oxidative stress [1–3]. While lipids are a well-known substrate for oxidation, proteins are also susceptible to oxidative modification with a variety of biological consequences including altered catalytic activity of enzymes, impaired IgG binding, altered protein degradation and others [4–10]. In addition to increased levels being found in aging and in patients with various inflammatory disorders, oxidized proteins have been identified in the serum of patients with end-stage renal disease [11–14] and in a manner analogous to oxidized lipids and atherosclerosis, they may serve not only as markers of oxidative stress, but may also contribute to various pathophysiological sequelae [15,16]. Hence it is plausible that oxidized serum proteins might contribute to atherosclerotic, infectious and other complications seen in end-stage renal disease.

While it is known that the serum of patients with end-stage renal disease contains increased levels of oxidized proteins, for patients on peritoneal dialysis (PD) the dialysate may also be a potential site where oxidized proteins could accumulate [17] and play a pathophysiological role in complications such as impaired ultrafiltration and other abnormalities [18,19]. Given that oxidized proteins may have adverse structural and functional consequences, as the dialysate dwells in the peritoneal cavity it is plausible that oxidized albumin and other proteins may interact with peritoneal mesothelial cells to initiate events that contribute to the development of ultrafiltration failure and peritoneal fibrosis. Oxidative stress has been demonstrated to play a role in the development of peritoneal membrane hyperpermeability and peritoneal fibrosis in rats [20]. However, little is known regarding the oxidized protein content of dialysate and no information is available as to how this may correlate with important clinical and laboratory variables including peritoneal membrane function. In this study we attempted to identify oxidized proteins in the dialysate of patients on PD using western blot analysis, and examined the relationship between the amounts of these proteins and the function of the peritoneal membrane and other clinical and laboratory variables.



   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
Patients and data collection
The Institutional Review Board at our hospital approved the study. All 18 of the adult patients in our PD program consented to data collection from chart review and to blood and dialysate sampling. Chart review was carried out and clinical and laboratory data were recorded including the results of peritoneal equilibration testing (PET), kt/V urea, protein catabolic rate (PCR) and creatinine clearance.

Sample collection
Five milliliters of blood was collected in serum separator tubes and the serum was isolated. During the same visit, peritoneal dialysate samples were taken at the time of PET testing following a 4-h dwell with 2 L of 2.5% dextrose dialysis solution (Baxter). The dialysate was centrifuged in 50 mL polypropylene tubes and the supernatant was isolated.

Western blot analysis
Western blot analysis for oxidized protein was performed on blood and dialysate samples as previously described [10,14,21]. Protein oxidation results in the formation of carbonyl groups that can be labeled with 2,4-dinitrophenylhydrazine (DNPH) to form stable protein hydrazones and can be identified using highly specific antibodies. Samples of dialysate and serum containing 1.5 µg protein were dissolved in 6% SDS, mixed with an equal volume of 10 mM DNPH and then incubated at room temperature for 15 min. Samples were then incubated with 7.5 µL of neutralization solution (OxyBlotTM, Chemicon, Temecula, CA, USA). Samples and a solution of protein molecular mass markers (Biorad, Hercules, CA, USA) were loaded onto 4–15% acrylamide gradient gels and subjected to SDS-PAGE under reducing conditions (by adding 2-mercaptoethanol to the sample mixture to achieve a final concentration of 0.74 M solution). Proteins were then electrophoretically transferred to nitrocellulose membranes, soaked in PBS-T (PBS, pH 7.2 containing 0.05% Tween 20) and then incubated on a rocker with blocking buffer (PBS-T containing 1% bovine serum albumin). Membranes were then incubated for 1 h with primary antibody (1:150) that is a rabbit antibody that specifically recognizes DNPH bound to oxidized protein (Oncor®). This antibody does not bind to free DNPH. Membranes were then rinsed twice with PBS-T and then incubated with PBS-T, once for 15 min then twice for 5 min each. Membranes were then incubated with secondary antibody (1:300) that is an HRP-conjugated goat antirabbit IgG for 1 h at room temperature. Membranes were then rinsed and incubated with PBS-T as was done following incubation with primary antibody. This was followed by incubation with ECL chemiluminescent reagent (Perkin-Elmer, Boston, MA, USA) and autoradiographs were produced using the Kodak X-OMAT AR film. In order to control for protein loading, membranes were stripped and reprobed using antibodies to human albumin. Band density was then determined using laser densitometry. For the oxidized protein autoradiographs, the predominant dense band at around 68 kD, corresponding to the molecular mass of albumin, was densitometrically measured. On the albumin autoradiographs, the same band at 68 kD was densitometrically measured. A ratio of the densitometry reading on the oxidized protein autoradiograph to the albumin autoradiograph was then determined for all samples. All experiments were carried out in quadruplicate.

Statistical analyses
Associations between categorical factors (24-h urine volume, PET test results) and continuous factors [oxidized protein/albumin ratio in the dialysate, oxidized protein/albumin ratio in serum, age, years on dialysis, years on PD and dry weight (kg)] were examined using the exact Mann–Whitney test. The association between 24-h urine volume and PET test result was examined using Fisher's exact test. Spearman correlation coefficients were computed to determine the degree of correlation between dialysate-oxidized protein/albumin ratios and serum-oxidized protein/albumin ratios. Spearman correlation coefficients were also computed for dialysate- and serum-oxidized protein/albumin ratios and each continuous factor to measure the degree of correlation between them. All statistical analyses were performed using the SAS/PC software package (SAS Institute Inc., Cary, NC, USA). P-values < 0.05 were considered statistically significant.



   Results
Top
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
Study population characteristics
Clinical and laboratory data for all patients are summarized in Table 1. The study group consisted of 18 adult patients 54.9 ± 15.8 years of age who had been on renal replacement therapy for a mean of 4.1 ± 4.4 years (range 0.3–19 years) with time on PD averaging 2.4 ± 1.7 years with a range of 0.3–5 years. Women constituted 44.4% of the group and African Americans, Asians and Caucasians were equally represented and together comprised 83.3% of the population. Two patients were Hispanic and one was Indian. Diabetes mellitus was the cause of renal failure in almost 40% of patients. Sixteen patients were on continuous cycler-assisted peritoneal dialysis (CCPD) while two were on continuous ambulatory peritoneal dialysis (CAPD). Total fill volumes prescribed with the goal of achieving kt/V targets [22] ranged from 10 to 18 L and kt/V urea exceeded 1.7 for all patients. No patient had suffered an episode of peritonitis nor had evidence of any other infection for at least 3 months before the study was conducted.


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  		Table 1 Study population characteristics

 
Western blot analysis for oxidized protein
The results of western blot analysis for oxidized protein using antibodies specific for DNPH-labeled oxidized protein followed by stripping and reprobing for albumin are summarized in Figure 1. A range of oxidized protein/albumin densitometric ratios can be seen both for dialysate and serum. For dialysate (Figure 1A), densitometric ratios of oxidized protein to albumin averaged 0.89 ± 0.42 with a minimum of 0.46 and maximum of 2.20. For serum (Figure 1B), ratios averaged 0.34 ± 0.09 with a range of 0.17–0.50. Figure 2 shows a representative western blot for oxidized protein with reprobing for albumin for the dialysate of all 18 patients.


Figure 1
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  		Fig. 1 Oxidized protein/albumin ratios for dialysate (A) and serum (B) in patients on peritoneal dialysis. Dialysate and serum samples were collected and labelled with 2,4-dinitrophenylhydrazine (DNPH). Samples were then subjected to western blot analysis using an antibody that is highly specific for DNPH-labeled oxidized proteins. Membranes were then stripped and reprobed for albumin. Band density was assessed using laser densitometry and ratios of oxidized protein to albumin were determined for each patient.

 

Figure 2
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  		Fig. 2 Representative western blot for oxidized protein and albumin in the dialysate of patients on peritoneal dialysis. Dialysate samples were collected as described in the Methods section, labeled with 2,4-dinitrophenylhydrazine (DNPH) and subjected to western blot analysis using antibodies highly specific for DNPH-labelled oxidized proteins followed by stripping and reprobing for albumin.

 
Relationship between oxidized dialysate protein and peritoneal membrane function
PET test results with characterization of membrane function as high/high average (10 patients) and low/low average (8 patients) and their relationship to dialysate- and serum-oxidized protein/albumin ratios and other continuous variables are presented in Table 2. Subjects with high/high average membranes were found to have higher oxidized protein/albumin ratios in their dialysate compared to patients with low/low average transport properties (1.08 ± 0.46 versus 0.65 ± 0.19, P < 0.01). No such relationship was evident between serum-oxidized protein/albumin ratios and membrane type, nor was there any correlation between oxidized protein/albumin ratios in the dialysate and the serum (r = –0.10). We also calculated ratios of oxidized protein to albumin in dialysate to that in the serum (a ratio of the ratios) and compared these between patients with high/high average and low/low average membranes. These ratios also were higher in the high/high average patients (3.52 ± 1.35 versus 1.89 ± 0.72, P < 0.01). Densitometric ratios of albumin in dialysate compared to serum were also determined and were also found to be higher in high/high average versus low/low average transporters (2.5 ± 0.5 versus 1.71 ± 0.7, P < 0.05), consistent with altered membrane function. There was no correlation between dialysate and serum albumin densitometric readings, suggesting that higher levels of albumin in the dialysate were not a direct consequence of higher levels of albumin in the serum, though direct measurements of albumin in the dialysate were not done. There was no significant association between age, years on dialysis, years on PD and dry weight with PET testing results. There also was no association between 24-h urine volume (<200 mL/day, ≥200 mL/day) and PET test results (data not shown). These findings suggest that greater amounts of oxidized protein in the dialysate are associated with high and high average membrane transport properties.


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  		Table 2 Summary statistics (median and interquartile range, mean and standard deviation) and the results of the exact Mann–Whitney test for patients grouped according to peritoneal membrane transport properties determined by PET testing

 
Oxidized dialysate protein and urine output
The relationship between 24-h urine volume [<200 mL (11 patients), ≥ 200 mL (7 patients)] and oxidized protein/albumin ratios in the dialysate and serum as well as other variables are presented in Table 3. Those with <200 mL urine output in 24 h had higher ratios of oxidized protein/albumin in the dialysate as compared to those with ≥200 mL urine output in 24 h (1.05 ± 0.46 versus 0.63 ± 0.14, P < 0.02). There was no association between 24-h urine volume and oxidized protein/albumin ratios in serum. Patients with ≥200 mL/day urine output had been on dialysis (both haemodialysis and PD) for relatively fewer years (mean of 2.2 ± 1.8 years) compared to those with <200 mL/day (mean 5.3 ± 5.1 years, P < 0.05). There was no statistically significant relationship between urine output and age, years on PD alone or dry weight. These findings suggest that diminished urine volume is associated with having higher quantities of oxidized protein in the dialysate.


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  		Table 3 Summary statistics (median and interquartile range, mean and standard deviation) and the results of the exact Mann–Whitney test for patients grouped according to 24-h urine volume

 
Oxidized dialysate protein and other laboratory and treatment variables
Spearman correlation coefficients were computed to assess the degree of correlation between oxidized protein/albumin ratios in the dialysate and serum with each continuous factor. These results are presented in Table 4. There was an association between a higher ratio of oxidized protein/albumin in the dialysate and lower serum albumin (P < 0.04), lower 24-h urine volume (P < 0.03) and lower creatinine clearance (P < 0.05). Of note, there was no significant correlation between oxidized protein/albumin ratios in the dialysate with kt/V or total PD fill volumes. With respect to serum-oxidized protein/albumin ratios, higher ratios correlated with lower kt/V (P < 0.04) and lower serum sodium (P < 0.01). There was no correlation with oxidized protein/albumin ratios in the serum and 24-h urine volume or creatinine clearance.


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  		Table 4 Spearman correlation coefficients for oxidized protein/albumin ratios and treatment and laboratory variables

 


   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
The findings in this study demonstrate the presence of oxidized proteins in the dialysate of patients on PD using western blot analysis, and suggest that higher levels of oxidized protein may be correlated with several clinical and laboratory abnormalities. There was an association between higher oxidized protein/albumin ratios in the dialysate and high/high average peritoneal membrane transport properties, diminished urine output, diminished creatinine clearance and lower serum albumin. Patients on PD may eventually develop varying degrees of ultrafiltration failure impairing the ability to achieve satisfactory fluid balance and may eventually result in an inability to continue this mode of renal replacement therapy [23]. The finding of greater amounts of oxidized protein in the dialysate of those patients with high/high average transport properties raises the possibility that increased levels of these proteins might contribute to injury to the peritoneal membrane and promote fibrogenesis and other events that can cause altered solute transport properties. This may take place through interactions of oxidized proteins with components of the peritoneal membrane including mesothelial cells and may result in the activation of signalling pathways that eventually lead to membrane damage and ultrafiltration failure. An alternative hypothesis is that the development of high/high average membrane transport properties is unrelated to the formation of oxidized proteins and their presence in increased quantities is an epiphenomenon. Given our small sample size and the design of our study, however, this must be regarded as speculative at present pending further studies.

The ratios of oxidized proteinto albumin were higher in the dialysate compared to serum suggesting a number of possibilities. Altered membrane transport of protein alone should not account for higher ratios and this suggests that proteins that have moved from the plasma to the dialysate might be undergoing oxidative modification within the peritoneal cavity itself in addition to some proteins that were oxidized in the serum and then entered the peritoneal cavity. This could be taking place because of a number of factors. As discussed further below, there may be variables present within the peritoneal cavity and dialysate including prooxidant effects of the dialysis fluid [17] that favour oxidative modification of proteins, and it is also plausible that in serum, the presence of antioxidant mechanisms may tend to suppress the formation of oxidized proteins and these mechanisms may be less active or inactive in the peritoneal cavity. While our findings may be suggestive of the generation of oxidized protein within the peritoneal cavity, changes in membrane properties could also affect the transport of albumin across the peritoneal membrane given that having a larger proportion of large pores in the setting of high and high average membrane transport properties may result in a change in the handling of oxidized proteins. If increased generation of oxidized protein in the peritoneal cavity were the main factor determining higher oxidized protein to albumin ratios in the dialysate, this would also suggest that these proteins could play a causative role in membrane damage and a consequent change in transport properties. Our study was limited by several factors including using a single sampling time point for dialysate testing and we plan further studies that will include time course measurements among other analyses to better define this process.

We also found that taking ratios of oxidized protein to albumin ratios in dialysate to that of oxidized protein to albumin in the serum (a ratio of the ratio) also yielded higher values in patients with high/high average versus low/low average membrane transport properties. This finding suggests that the incremental increase in the oxidized protein to albumin ratio is an important factor in patients with high/high average type membranes, though a causative relationship cannot yet be determined.

Other factors could potentially contribute to the appearance of oxidized protein in the dialysate. One plausible factor might be the dosage of dialysis delivered, meaning that better dialyzed PD patients might suffer less of an inflammatory state and hence a lessened propensity to form oxidized proteins. As summarized in Table 4, we found that decreased urine volume as a measure of residual renal function and decreased creatinine clearance were both correlated with higher levels of oxidized protein in the dialysate. Similarly, we found that oxidized protein to albumin ratios in the serum were negatively correlated with kt/V. It is known that there are multiple systemic correlates of loss of residual renal function including its ability to predict mortality [24] and an apparently more rapid decline in ultrafiltration capacity in patients on automated PD [25]. Also of note, Lameire et al. have reported that plasma levels of oxidized proteins are lower in patients on PD [26] and, given that patients on PD are more likely to maintain some degree of residual renal function compared to those on haemodialysis, this also suggests that residual renal function may bear some relationship to oxidized protein generation. While our small sample size could account for discrepancies between dialysate and serum findings, these results nevertheless suggest a correlation between higher levels of oxidized proteins and uraemic toxicity.

Also of note, we found that higher oxidized protein levels in the dialysate demonstrated a negative correlation with serum albumin levels. This finding appears to be consistent with prior demonstrations of a relationship between hypoalbuminaemia, oxidative stress and inflammation in haemodialysis patients [27]. However, it is plausible that this could simply be the result of mathematical coupling as patients with higher serum albumin levels would be expected to have higher dialysate albumin levels, hence making the ratios lower. We did not find a correlation between serum and dialysate albumin levels making this explanation somewhat less likely, though further study is needed.

How oxidation reactions may occur within the peritoneal cavity of patients on PD and how this may affect the development of peritoneal fibrosis has been the subject of several investigations, and evaluating the role of oxidative stress by means of deoxycholate and other methods have provided substantial insights [28–32]. Glucose and the formation of glucose degradation products (GDPs) and advanced glycation end products (AGEs) that interact with the receptor for AGE (RAGE) likely have an important contributions as well via enhanced oxidative stress and other mechanisms [33–40]. Further evidence supporting a role of oxidant stress in peritoneal membrane fibrosis and hyperpermeability comes from studies demonstrating reversal of these changes with the antioxidant N-acetylcysteine and angiotensin II receptor blocker treatment [20]. In addition, administration of the oxidant stress inhibitor trimethazidine has been shown to decrease levels of vascular endothelial growth factor and the activity of glutathione reductase and to decrease peritoneal membrane thickness in a rat model [41]. These findings raise the question of whether antioxidant therapy might ameliorate the formation of oxidized proteins in the dialysate and limit the development of peritoneal damage. However, it is unknown whether in humans the administration of antioxidants could lessen the formation of oxidized proteins in the dialysate or whether this would diminish the likelihood of developing peritoneal membrane ultrafiltration failure.

In addition to the importance of determining the mechanism of oxidized protein generation, further studies will need to address a more precise quantitation of protein oxidation in terms of the percentage of proteins that are modified. In our study the ratios themselves do not provide an absolute quantitation of how much protein oxidation took place. However, data from our prior work as well as work of others might provide some insights. In a prior study [14] we reported increased oxidized IgG in the serum of patients on haemodialysis. In that study, we found on average nearly a doubling in the oxidized protein content of the IgG in these patients compared to controls. It has been estimated that a basal level of protein oxidation in healthy individuals represents oxidative modification of ~10% of all proteins [42] and hence a doubling could represent ~20% or so of proteins being oxidatively modified. Hence if a doubling of protein oxidation were to take place in patients on PD then perhaps 20% or so of their serum proteins may have undergone oxidative modification. There is no control available for dialysate as all samples were of course from patients with end-stage renal disease on PD in the present study; though we could probably estimate that the percentage of protein oxidation there was even higher, though at present this is speculative.

In summary, oxidized protein can be identified in the dialysate of patients on PD using western blot analysis. Higher dialysate-oxidized protein content appears to correlate with high/high average membrane transport properties, loss of residual renal function, lower serum albumin levels and lower creatinine clearance. These preliminary findings suggest the possibility that there may be a relationship between oxidized proteins in dialysate and the development of impaired membrane function in patients on PD.



   Acknowledgments
 
We gratefully acknowledge the assistance of our peritoneal dialysis nursing staff including Kathleen Wechsler, Joanne Muccio and Denise Sweeney.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

  1. Himmelfarb J, Hakim RM. Oxidative stress in uremia. Curr Opin Nephrol Hypertens (2003) 12:593–598.[Web of Science][Medline]
  2. Vaziri ND. Oxidative stress in uremia: nature, mechanisms and potential consequences. Semin Nephrol (2004) 24:469–473.[Web of Science][Medline]
  3. Oberg BP, McMenamin E, Lucas FL, et al. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int (2004) 65:1009–1016.[CrossRef][Web of Science][Medline]
  4. Stadtman ER, Arai H, Berlett BS. Protein oxidation by the cytochrome P450 mixed-function oxidation system. Biochem Biophys Res Commun (2005) 338:432–436.[CrossRef][Web of Science][Medline]
  5. Stadtman ER. Protein oxidation in aging and age-related diseases. Ann NY Acad Sci (2001) 928:22–38.[Web of Science][Medline]
  6. Chevion M, Berenshtein E, Stadtman ER. Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic Res (2000) 33(Suppl):S99–S108.[Web of Science][Medline]
  7. Teoh CY, Davies KJ. Potential roles of protein oxidation and the immunoproteasome in MHC class I antigen presentation: the ‘PrOxI’ hypothesis. Arch Biochem Biophys (2004) 423:88–96.[CrossRef][Web of Science][Medline]
  8. Naskalski JW, Marcinkiewicz J, Drozdz R. Myeloperoxidase-mediated protein oxidation: its possible biological functions. Clin Chem Lab Med (2002) 40:463–468.[CrossRef][Web of Science][Medline]
  9. Sohal RS. Role of oxidative stress and protein oxidation in the aging process. Free Radic Biol Med (2002) 33:37–44.[CrossRef][Web of Science][Medline]
  10. Mattana J, Margiloff L, Chaplia L, et al. Metal-catalyzed oxidation of extracellular matrix increases macrophage nitric oxide generation. Kidney Int (1998) 54:1581–1592.[CrossRef][Web of Science][Medline]
  11. Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int (1996) 49:1304–1313.[Web of Science][Medline]
  12. Donate T, Herreros A, Martinez E, et al. Protein oxidative stress in dialysis patients. Adv Perit Dial (2002) 18:15–17.[Medline]
  13. Miyata T, Izuhara Y, Sakai H, et al. Carbonyl stress: increased carbonyl modification of tissue and cellular proteins in uremia. Perit Dial Int (1999) 19(Suppl_2):S58–S61.[Abstract/Free Full Text]
  14. Ahmed S, Gibbons N, Mattana J. Oxidized immunoglobulin G in patients with end-stage renal disease treated by hemodialysis. Ann Clin Lab Sci (2003) 33:11–17.[Abstract/Free Full Text]
  15. Witko-Sarsat V, Gausson V, Descamps-Latscha B. Are advanced oxidation protein products potential uremic toxins? Kidney Int Suppl (2003) 84:S11–S14.[Medline]
  16. Drueke TB, Massy ZA. Advanced oxidation protein products, parathyroid hormone and vascular calcification in uremia. Blood Purif (2002) 20:494–497.[CrossRef][Web of Science][Medline]
  17. Ruiz MC, Portero-Otin M, Pamplona R, et al. Chemical and immunological characterization of oxidative nonenzymatic protein modification in dialysis fluids. Perit Dial Int (2003) 23:23–32.[Abstract/Free Full Text]
  18. Flessner MF. Peritoneal ultrafiltration: mechanisms and measures. Contrib Nephrol (2006) 150:28–36.[Web of Science][Medline]
  19. Parikova A, Smit W, Struijk DG, et al. Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure. Kidney Int (2006) 70:1988–1994.[Web of Science][Medline]
  20. Noh H, Kim JS, Han KH, et al. Oxidative stress during peritoneal dialysis: implications in functional and structural changes in the membrane. Kidney Int (2006) 69:2022–2028.[CrossRef][Web of Science][Medline]
  21. Chow A, Ahmed S, Chaplia L, et al. Measurement of immunoglobulin G oxidation by western blot analysis. In: Methods in Molecular Biology. Oxidants and Antioxidants. Ultrastructure and Molecular Biology Protocols—Armstrong D, ed. (2002) 196. Totawa, NJ: Humana Press. 163–169.
  22. Lo WK, Bargman JM, Burkart J, et al, ISPD Adequacy of Peritoneal Dialysis Working Group. Guideline on targets for solute and fluid removal in adult patients on chronic peritoneal dialysis. Perit Dial Int (2006) 26:520–522.[Free Full Text]
  23. Flessner MF. The effect of fibrosis on peritoneal transport. Contrib Nephrol (2006) 150:174–80.[Web of Science][Medline]
  24. Bargman JM, Golper TA. The importance of residual renal function for patients on dialysis. Nephrol Dial Transplant (2005) 20:671–673.[Free Full Text]
  25. Davies SJ, Brown EA, Frandsen NE, et al, EAPOS Group. Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription. Kidney Int (2005) 67:1609–1615.[CrossRef][Web of Science][Medline]
  26. Lameire N, Vanholder R, De Smet R. Uremic toxins and peritoneal dialysis. Kidney Int Suppl (2001) 78:S292–S297.[Medline]
  27. Danielski M, Ikizler TA, McMonagle E, et al. Linkage of hypoalbuminemia, inflammation and oxidative stress in patients receiving maintenance hemodialysis therapy. Am J Kidney Dis (2003) 42:286–294.[CrossRef][Web of Science][Medline]
  28. Gotloib L, Wajsbrot V, Cuperman Y, et al. Acute oxidative stress induces peritoneal hyperpermeability, mesothelial loss, and fibrosis. J Lab Clin Med (2004) 143:31–40.[CrossRef][Web of Science][Medline]
  29. Korybalska K, Breborowicz A, Martis L, et al. In vitro detection of hydrogen peroxide in mesothelial cells. Adv Perit Dial (1996) 12:7–10.[Medline]
  30. Yamaji Y, Nakazato Y, Oshima N, et al. Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution. Nephrol Dial Transplant (2004) 19:2592–2597.[Abstract/Free Full Text]
  31. Lee HB, Yu MR, Song JS, et al. Reactive oxygen species amplify protein kinase C signaling in high glucose-induced fibronectin expression by human peritoneal mesothelial cells. Kidney Int (2004) 65:1170–1179.[CrossRef][Web of Science][Medline]
  32. Grzybowski AE. Antioxidant mechanisms in human peritoneal mesothelial cells (HPMC) exposed in vitro to the constituents of dialysis fluid. Med Sci Monit (2000) 6:232–239.[Medline]
  33. Zeier M, Schwenger V, Deppisch R, et al. Glucose degradation products in PD fluids: do they disappear from the peritoneal cavity and enter the systemic circulation? Kidney Int (2003) 63:298–305.[CrossRef][Web of Science][Medline]
  34. Shostak A, Pivnik E, Gotloib L. Cultured rat mesothelial cells generate hydrogen peroxide: a new player in peritoneal defense? J Am Soc Neph (1996) 7:2371–2378.
  35. Nevado J, Peiro C, Vallejo S, et al. Amadori adducts activate nuclear factor-kappaB-related proinflammatory genes in cultured human peritoneal mesothelial cells. Br J Pharmacol (2005) 146:268–279.[CrossRef][Web of Science][Medline]
  36. Schwenger V, Morath C, Salava A, et al. Damage to the peritoneal membrane by glucose degradation products is mediated by the receptor for advanced glycation end-products. J Am Soc Nephrol (2006) 17:199–207.[Abstract/Free Full Text]
  37. Boulanger E, Wautier MP, Wautier JL, et al. AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression. Kidney Int (2002) 61:148–156.[CrossRef][Web of Science][Medline]
  38. Ding Y, Kantarci A, Hasturk H, et al. Activation of RAGE induces elevated O2-generation by mononuclear phagocytes in diabetes. J Leukoc Biol (2007) 81:520–527.[Abstract/Free Full Text]
  39. Miyata T, Hori O, Zhang J, et al. The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2 microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis. J Clin Invest (1996) 98:1088–1094.[Web of Science][Medline]
  40. Yamamoto Y, Kato I, Doi T, et al. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest (2001) 108:261–268.[CrossRef][Web of Science][Medline]
  41. Gunal AI, Celiker H, Ustundag B, et al. The effect of oxidative stress inhibition with trimetazidine on the peritoneal alterations induced by hypertonic peritoneal dialysis solution. J Nephrol (2003) 16:225–230.[Web of Science][Medline]
  42. Stadtman ER. Protein oxidation and aging. Science (1992) 257:1220–1224.[Abstract/Free Full Text]
Received for publication: 11. 7.07
Accepted in revised form: 31. 3.08


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