Efecto del tratamiento con hemodiálisis sobre el estrés oxidativo en pacientes con insuficiencia renal crónica / Effect of oxidative stress in patients with chronic renal failure

RESUMEN

La enfermedad cardiovascular sigue siendo la principal causa de morbi-mortalidadde los pacientes con enfermedad renal crónica en tratamiento dialítico. Losllamados factores de riesgo tradicionales no son capaces de explicar la alta incidenciade estos sucesos por lo que cada vez más se está buscando nuevos factoresde riesgo. Entre ellos el estrés oxidativo aumentado en estos pacientes podríaser un contribuyente importante en el riesgo cardiovascular.Métodos: Para evaluar los efectos del tratamiento con hemodiálisis hemos realizadoun estudio completo del estrés oxidativo en 15 pacientes urémicos. Hemosanalizado enzimas antioxidantes representativas como la superoxidodismutasa, catalasay glutation peroxidasa, junto con el cociente entre glutation oxidado y reducidoy otros indicadores de oxidación como el malonildialdehído y la 8-oxo-2´-deoxiguanosina. El análisis se ha realizado en pacientes hemodializados antes ydespués del tratamiento dialítico y se ha comparado con un grupo control de 16voluntarios sanos.Resultados: Encontramos un aumento de todos los parámetros de oxidación respectoa los del grupo control antes de la hemodiálisis con un descenso significativotras la misma. Los parámetros antioxidantes son significativamente menoresrespecto a los de los controles con mejoría tras la hemodiálisis.Conclusiones: Nuestros resultados sugieren que la hemodiálisis por sí misma podríacorregir el estado pro-oxidante de nuestros pacientes. En el trabajo se analizanlos posibles mecanismos implicados en los cambios en el estrés oxidativo conla hemodiálisis

ABSTRACT

Background: Cardiovascular disease remains the single most common cause ofexcess morbidity and mortality in end-stage renal disease (ESRD) patients and thetraditional risk factors can’t explain the high incidence of these events. New «non-traditional» risk factors are analysed in uremic patients and the increasedoxidative stress is postulated to be an important contributor to uremic cardiovascularrisk.Methods: In order to evaluate the effects of the hemodialysis treatment, a completeoxidative stress study was performed in fifteen uremic patients. Representativeantioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) andglutathione peroxidase (GPx), together with oxidized/reduced glutathione ratio(GSSG/GSH) and other oxidation indicators including malondialdehyde (MDA)and 8-oxo-2´-deoxyguanosine (8-oxo-dG), were analysed to assess oxidative stressstatus in normal control volunteers and in uremic patients treated with hemodialysis(HD). In the latter group blood samples were taken prior and after HDto evaluate the effect of the session of HD over the oxidative markers.Results: Low levels of antioxidant enzyme activities were observed in the uremicpatients as compared with normal control subjects. HD treatment results ina significant recovery of these enzyme activities but remain lower as comparedwith control values. Levels of GSSG and GSH concentrations were increased andreduced respectively in uremic patients. These differences were even higher beforethe HD and were reduced upon treatment to levels closer to those observedin controls. MDA levels and 8-oxo-dG levels were also increased in uremic patientswith the highest values observed in the pre-treated HD group. EventhoughHD treatment decreases the levels of oxidation products in mononuclear cells ofuremic patients the values of the control group are not reached.Conclusions: Our results suggest that hemodialysis by itself could correct theoxidative status in these patients. The possible mechanisms involved in the oxidativestress changes with the hemodialysis treatment will be discussed below