Efecto oxidativo de la administracion de hierro intravenoso en hemodialisis respuesta celular y disfuncion endotelial secundarias eficacia de la administracion profilactica de n acetilcisteina (nac)

Resumen

The aim of study is to analyze the effect of intravenous i ron (iVFe) administration in haemodialysis (HD) patients on the oxidative stress, including the inflammatory response (neutrophil and monocyte activation) and the endothelial dysfunction. Afterwards we intend to test the hypothesis that mi ñor dose of i ron or a dose of NAC attenuates these events and, in that case, to stablish a possible protocol of iVFe administration with minimun oxidative effects. The study includes 40 chronic renal patients undergoing regular without the use of drugs with antioxidant effect in the last month. All of them were receiving iVFe every two weeks for the last month. They received HD treatment three times a week with a low-flux polysulphone membrane. All patients were investigated in a cross-over design, 15 days apart with or without suplementation of a single IV dose of NAC (2 g dilute with 50 mL of sterile Dextrose 5% solution) infuse 15 minutes before the iVFe infusión (100 mg or 50 mg of i ron (iil)-hydroxide sucrose complex which was diluted with sterile 0,9% saline solution). The i ron infusión was done during the second hour of HD and ever in the mid-week session. To further explore the effect of HD and NAC independently, the study was carried out in two different midweek sessions in which saline solution and NAC, respectively, were used. Blood samples were drawn before HD (baseline) and 60 and 240 min after starting i ron infusión. The followings determinations will be performed: Respiratory Burst Test, CDllb/CDl8 (Mac-1) expression by neutrophiles and monocytes, intracellular and plasmàtic levéis of TNF-alfa and IL-8, Total Antioxidant Capacity (TAC) in plasma and plasmàtic levéis of glutation, malondyaldehyde (MDA), sICAM-1 and antigenic von willebrand Factor (vWF). Hemoglobin and serum i ron, ferri tin, transferrin, albumin, uric acid and c reactive protein levéis will be also performed. Mul ti factorial ANOVA was performed with the following factors: treatment and time as fixed factors and groups and patients (nested within groups) as random factors. The interaction between both fixed factors was also examined. Subsequently, a Student-Newman-Keuls pairwise comparison test was done, as appropriate. To remove the potential effects of pre-existing individual differences between subjects at baseline, ANCOVA also was carried out. Statistical significance was set at p <0.05 (SPSS vll.0)%&/Significant increase in CDllb/CDl8 expression in monocytes, plasmatic IL-8 level, oxidative respiratory activity in neutrophils, MDA levéis and slCAM-1 and vWF levéis were found respect to the effect of HD. Plasmatic TAC decreased during HD. Treatment with iVFe sucrose was accompanied by an increase in intracellular IL-8 in monocytes. This effect was seen shortly after iVFe infusión and neither was accompanied by the increase of other intracellular cytokines as the TNF-á nor was modified by previ ous administration of NAC. This phenomenon has also been observed in a model of tolerance to LPS with other cytokines (IL-1 and TNF-á) in our Laboratory. Treatment with iVFe sucrose also increases MDA levéis at 60 and this effect was similar to the effect of HD at 240 min. NAC treatment could compénsate increase of MDA levéis related to 50 mg of iVFe and increases of plasmatic TAC and MDA levéis related to HD effect.