Nephrol Dial Transplant (2003) 18: 1272-1280
© 2003 European Renal Association-European Dialysis and Transplant Association
Consensus Paper
Oxidative stress in end-stage renal disease: an emerging threat to patient outcome
1 Department of Nephrology and Dialysis, Azienda Ospedale di Lecco, Ospedale A. Manzoni, Lecco, Italy 2 Service de Nephrologie, Hôpital Lapeyronie, Montpellier, France 3 Department of Nephrology and Medical Intensive Care, Charité, Campus Virchow Klinikum, Berlin, Germany 4 Division of Renal Medicine, Department of Clinical Science, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden 5 Division of Nephrology, University Hospital Würzburg, Germany and 6 CNR Centre of Clinical Physiology, Reggio Calabria, Italy
Abstract
Introduction. Patients affected by end-stage renal disease (ESRD) experience an excess of morbidity and mortality due to cardiovascular disease (CVD), which cannot be fully explained by the classical CVD risk factors. Among emerging CVD risk factors, oxidative stress is currently being given emphasis.
Methods. We achieved a consensus on key points relating to oxidative stress in ESRD patients.
Results. ESRD patients are subjected to enhanced oxidative stress, as a result of reduced anti-oxidant systems (vitamin C and selenium deficiency, reduced intracellular levels of vitamin E, reduced activity of the glutathione system) and increased pro-oxidant activity (advanced age, high frequency of diabetes, chronic inflammatory state, uraemic syndrome, bio-incompatibility of dialysis membranes and solutions). Oxidative stress and inflammation are deeply inter-related, as different oxidant free radicals are generated by phagocytic cells in response to inflammatory stimuli: both are related to endothelial dysfunction, as the endothelium is a source and a target of oxidants and participates in the inflammatory response. There is growing evidence, from experimental and clinical studies, that oxidative stress may be implicated in the pathogenesis of atherosclerosis and other complications of ESRD, namely dialysis-related amyloidosis, malnutrition and anaemia. Given that free radicals have very short half-lives (seconds), the clinical assessment of oxidative stress is based on the measurement of different stable oxidized compounds (such as lipid peroxidation products, advanced glycation and oxidation lipid and protein products, nucleic acid oxidation derivatives) or antibodies directed against oxidized epitopes (such as anti-oxidized low-density lipoprotein antibodies). At the same time, both enzymatic anti-oxidants (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic anti-oxidants (glutathione, vitamin C, vitamin E, negative inflammatory proteins) can be evaluated. However, many laboratory methods assessing various oxidative stress components still have to be standardized. Moreover, it is still uncertain whether it is better measuring plasma and/or intracellular concentrations or activities of these components. The possibility of improving patient outcome by therapeutic interventions aimed at reducing oxidative stress, e.g. by vitamin C or vitamin E supplementation, currently is to the fore, but results so far have remained inconclusive.
Conclusions. It is important to consider oxidative stress as a potentially important source of patient morbidity and mortality, although this knowledge is not yet immediately applicable in the clinical arena. Further well-designed, randomized controlled clinical trials with anti-oxidants (e.g. vitamin E, vitamin C, N-acetyl cysteine, L-arginine) are required to establish evidence-based recommendations for clinical practice.
Keywords: anti-oxidant therapy; atherosclerosis; dialysis complications; endothelial dysfunction; inflammation; oxidative stress
Notes
Correspondence and offprint requests to: Professor Francesco Locatelli, Department of Nephrology and Dialysis, Ospedale A. Manzoni, Via Dell'Eremo 11, 23900 Lecco, Italy. Email: nefrologia{at}ospedale.lecco.it
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