This inflammatory effect is also seen in patients under both types of RRT. From the results obtained, it can be predicted that PD exhibits the most deleterious effect on the endothelium and, interestingly, current HD techniques have diminished the harmful effect previously ascribed to this treatment. Previous studies by our group and others were mostly performed in hemodialyzed patients. Results have demonstrated the existence of endothelial activation and damage in CKD both in vivo and in vitro. Plasma levels of endothelium-derived proteins, some of them vasoactive factors, are increased in these patients. Endothelium-dependent vasodilation, the gold-standard method to assess endothelial function in vivo, is also decreased in these patients. Exposure of cultured EC to sera from hemodialyzed patients accelerates cell cycle and proliferation, with a more prothrombotic extracellular matrix and a proinflammatory phenotype with a higher expression of cell adhesion molecules, which represents one of the earliest pathological Vorinostat changes in immune and inflammatory diseases such as atherosclerosis. Moreover, a proteomic characterization of these changes demonstrated a differential expression of proteins associated with inflammation and oxidative stress in cells exposed to the uremic condition, related to the NFkB signaling pathway. In fact, exposure of endothelial cells in culture to sera from hemodialyzed patients induces activation of p38 MAPK and of NFkB. In hemodialyzed patients there is presence of the uremic toxics but also of those components released by blood cells that become activated by the procedure itself. However, results from the present study indicate that there is not an additional deleterious effect of hemodialysis over that observed in the predialysis condition. Probably, the generalized use of more biocompatible dialysis membranes and ultrapure water, among other advances, has reduced blood cell stress with less contribution of proinflammatory cytokines. Interestingly, PreD patients showed a more significant inflammatory state than HD patients. These results are not fully in agreement with those by Merino et al.. In their study, PD seems to exhibit a lower damaging condition on the endothelium than HD and predialysis. Differences between both studies may be due to the different experimental approaches applied but especially to the fact that in our study patients with CKD did not have evidence of previous cardiovascular disease and other known cardiovascular risk factors. The present study provides the first evidence that sera from PD patients have a greater activating effect on p38 MAPK and NFkB, two intracellular key markers of inflammation and cell damage. The p38 MAPK protein kinases affect a variety of intracellular responses, with well-recognized roles in inflammation, cell-cycle regulation, cell death, development, differentiation, senescence and tumorigenesis. NFkB seems to act by regulating the expression of several genes involved in tumorigenesis, including anti-apoptotic proteins, cyclooxygenase-2, matrix metalloproteinase-9, genes encoding adhesion molecules, chemokines, and inflammatory cytokines; and cell cycle regulatory genes. Therefore, both p38 MAPK and NFkB participate in the proinflammatory responses and exhibit a clear role in the development of inflammatory and immunological diseases. According to the USRDS 2011 Annual Data Report, mortality rates of dialyzed patients have declined in the last years.