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Raymond Vanholder,
Nathalie Meert,
Eva Schepers,
Griet Glorieux,
Angel Argiles,
Philippe Brunet,
Gerald Cohen, Tilman Drüeke,
Harald Mischak,
Goce Spasovski,
Ziad Massy,
Joachim Jankowski
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ABSTRACT: The aim of this manuscript is to initiate a constructive discussion about deviations in measured concentrations of uraemic solutes; these deviations, if not perceived or handled appropriately, may lead to incorrect interpretations of the pathophysiological role of uraemic solutes and/or to erroneous therapeutic decisions. To come to an objective approach towards this problem, variability analysis of reported concentrations may be of help. Striking outliers should either be discarded or considered together with other values which are more consistent with the majority of reported data.
Nephrology Dialysis Transplantation 12/2007; 22(11):3115-21. · 3.40 Impact Factor
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Natalie Meert,
Eva Schepers,
Rita De Smet,
Angel Argiles,
Gerald Cohen,
Reinhold Deppisch, Tilman Drüeke,
Ziad Massy,
Goce Spasovski,
Bernd Stegmayr,
Walter Zidek,
Joachim Jankowski,
Raymond Vanholder
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ABSTRACT: Discrepancies in reported uremic toxin concentrations were evaluated for 78 retention solutes. For this analysis, 378 publications were screened. Up to eight publications per toxin were retained. The highest and the lowest reported concentrations, as well as the median reported concentration were registered. The ratio between the highest and the lowest (H/L) concentrations and, for some solutes, also the ratio between the highest and the median (H/M) concentrations were calculated. The compounds were arbitrarily subdivided into three groups based on their H/L ratio: group A, H/L < 3 (n = 33); group B, 3 < H/L < 8.5 (n = 20); and group C, H/L > 8.5 (n = 25). Solutes of groups A and B showed a low to intermediate scatter, suggesting a homogeneity of reported data. Group C showed a more substantial scatter. For at least 10 compounds of group C, extremely divergent concentrations were registered (H/M > 5.5) using scatter plot analysis. For all solutes of groups A and B, the highest reported concentration could be used as a reference. For some solutes of group C and for the compounds showing a divergent scatter analysis, however, more refined directives should be followed.
Artificial Organs 09/2007; 31(8):600-11. · 2.00 Impact Factor
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Nephrology Dialysis Transplantation 01/2007; 21(12):3354-7. · 3.40 Impact Factor
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ABSTRACT: In haemodialysis (HD) patients, advanced oxidation protein products (AOPP) were previously ascribed to oxidized plasma proteins, resulting mainly from increased myeloperoxidase (MPO) activity. The aim of the present study was to assess the mechanisms leading to the generation of AOPP during the course of chronic kidney disease including end-stage renal disease, with particular focus on AOPP and MPO characterization in the plasma at decreasing levels of kidney function.
Phagocyte activation was evaluated by whole blood NADPH oxidase and MPO activities. In plasma, MPO protein concentration was quantified by ELISA and catalytic activity assayed by the spectrophotometric detection of phenol and 4-aminoantipyrine (AAP) co-oxidation in the presence of hydrogen peroxide (H(2)O(2)).
In HD patients, plasma AOPP concentration was linked to neutrophil oxidative activity. Such an association was not found in control subjects or predialysis patients, suggesting that in the latter, AOPP generation did not mainly result from MPO released by activated neutrophils. Similarly, plasma AOPP correlated with plasma MPO protein concentration in HD patients, but not in control subjects or predialysis patients, suggesting that in the latter AOPP did not predominantly result from MPO activity. This interpretation was supported by the observation of a greater degree of co-oxidation of phenol and AAP in the absence of H(2)O(2) in predialysis patients than in HD patients or control subjects. The contribution of MPO dramatically differed between predialysis and HD patients (2+/-5 vs 46+/-6%; P<0.001).
Our observations suggest that AOPP generation in predialysis patients mainly results from MPO-independent oxidation mechanisms.
Nephrology Dialysis Transplantation 06/2006; 21(6):1555-63. · 3.40 Impact Factor
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Nephrology Dialysis Transplantation 09/2004; 19(8):1951-5. · 3.40 Impact Factor
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Nephrology Dialysis Transplantation 05/2004; 19(4):1020-1. · 3.40 Impact Factor
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ABSTRACT: AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A potential target forN-acetylcysteine treatment in dialysis patients.
Oxidative stress largely contributes to hemodialysis-associated lethal complications, thus explaining the urgent need of antioxidant-based therapeutic strategies in hemodialysis patients. We previously identified advanced oxidation protein products (AOPP) in the uremic plasma as exquisite markers of oxidative stress and potent mediators of monocyte activation. The present study was aimed at searching whether (1) AOPP can also trigger activation of polymorphonuclear neutrophils (PMN), and (2) whether AOPP-induced activation could be inhibited by N-acetylcysteine (NAC), a widely used compound which has been shown to prevent oxidative injury to kidney.
Both human serum albumin (HAS) AOPP (i.e., HOCl-modified HSA in vitro preparations and AOPP extracted from plasma of hemodialysis patients) were tested for their capacity to trigger phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO)-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence (CL), respectively, as compared to receptor-dependent [opsonized zymosan or receptor-independent phorbol myristate acetate (PMA)]. The effect of PMN priming by platelet-activating factor (PAF), and the effect of NAC on normal monocyte and on normal or hemodialysis patient's (N = 16) PMN oxidative responses were compared.
HSA-AOPP triggered in a HOCl dose-dependent manner both NADPH-oxidase- and MPO-dependent CL of PMN. This latter was further enhanced by PAF priming. Plasma-derived AOPP obtained from hemodialysis patients also triggered PMN respiratory burst. NAC significantly reduced HSA-AOPP-mediated responses of normal monocyte and of normal and uremic PMN but had no significant effect on opsonized zymosan- or PMA-induced CL responses.
This dual potential of NAC to inhibit phagocyte oxidative responses induced by HSA-AOPP without affecting those mediated by compounds mimicking pathogens supports the proposal of a therapeutic trial with NAC aimed at reducing oxidative stress-related inflammation in hemodialysis patients.
Kidney International 08/2003; 64(1):82-91. · 6.61 Impact Factor
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ABSTRACT: Increased common carotid artery intima-media thickness (CCA-IMT) is a marker of early atherosclerosis. Low-grade inflammation is associated with the pathogenesis of atherosclerosis. Low-grade inflammation and increased CCA-IMT are observed in end-stage renal disease (ESRD). Oxidative stress is involved in uremia-related inflammation. Advanced oxidation protein products (AOPP) are markers of oxidant-mediated protein damage in ESRD. Intravenous iron given to patients on hemodialysis (HD) might induce oxidative stress. We investigated the relationships between AOPP, iron therapy, and CCA-IMT in stable HD patients.
Plasma AOPP and blood chemistry, including iron status, were analyzed in a cohort of 79 ESRD patients on HD. Measurements of CCA-IMT and CCA diameter, as assessed by B-mode ultrasonography, were obtained in 60 patients. AOPP levels were elevated in ESRD patients, and in univariate (r=0.42, P<0.0001) and multivariate analyses (r=0.38, P<0.001), they correlated with serum ferritin and with the intravenous iron dose received during the 12 months preceding the study (ferritin, P<0001; AOPP, P<0.01). Univariate and multivariate analyses identified the AOPP concentration as being significantly associated with CCA-IMT (P=0.0197) and CCA wall-to-lumen ratio (r=0.560, P<0.0001). Independently of AOPP concentration, cumulative iron dose was positively related to CCA-IMT (P=0.015) in patients <60 years.
In ESRD patients, CCA-IMT and CCA wall-to-lumen ratio were associated with plasma AOPP, serum ferritin, and the annual intravenous iron dose administered. These findings support the concept of a role of oxidative stress in the early atherosclerosis of ESRD patients, which may be increased by the usually recommended doses of intravenous iron.
Circulation 10/2002; 106(17):2212-7. · 14.74 Impact Factor
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ABSTRACT: Oxidative stress, which results from a rupture in the natural balance between pro- and antioxidant systems, is considered as a major factor in dialysis-associated morbidity and mortality. Emerging pharmacologic and dialytic antioxidant therapeutic and dialysis strategies should enable us to reduce the harmful consequences of oxidative stress in dialysis patients. Moreover, since there is increasing evidence of oxidative stress long before the initiation of maintenance dialysis, antioxidant therapeutic strategies should probably be developed very early in the course of renal failure.
Seminars in Dialysis 04/2001; 14(3):193 - 199. · 2.27 Impact Factor
