Uremia impairs blood dendritic cell function in hemodialysis patients

© 2008 International Society of NephrologyPatients on hemodialysis have a general immunodeficiency involving both innate and adaptive responses. As the mechanisms contributing to this defect are uncertain, we sought to study the effects of uremia on circulating dendritic cells (DC) in hemodialysis patients. Immunomagnetic beads were used to isolate myeloid and plasmacytoid DCs from healthy donors. Immune-related functions were determined in these cells cultured in either a complete media containing ABO-compatible serum or media containing sera from uremic patients. The myeloid cells were analyzed for costimulatory molecule expression and allo-stimulatory capability following lipopolysaccharide stimulation. The production of interferon-alpha following herpes-simplex virus stimulation by the plasmacytoid cells was also measured. Myeloid DCs incubated with uremic sera demonstrated impaired maturation and decreased allo-stimulatory capacity. Similarly, herpes virus-stimulated plasmacytoid DCs incubated with uremic sera produced significantly less interferon-alpha compared with cells incubated in the complete media. Both small and large molecule uremic toxins inhibited DC functions in vitro. Use of more efficient dialysis to improve small molecule clearance reversed the inhibition of uremic sera on myeloid but not plasmacytoid DC function. We have shown that the immunodeficiency of hemodialysis patients is due to dialyzable uremic toxins.W H Lim, S Kireta, G R Russ and P T Coate

Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients

Copyright © 2007 International Society of NephrologyPatients with chronic renal failure maintained on intermittent hemodialysis have frequent infections and a suboptimal response to vaccinations. Dendritic cells are potent antigen-presenting cells essential for the initiation and maintenance of innate and adaptive immunity. In this study we used uremic sera from hemodialysis patients to measure its impact on monocyte and monocyte-derived dendritic cell function in vitro. Monocytes from healthy and uremic subjects were isolated using immunomagnetic beads and differentiated into dendritic cells in the presence of either complete sera or sera from hemodialysis patients. Dendritic cells from normal patients cultured in uremic sera had decreased endocytosis and impaired maturation. These cells, however, had enhanced IL-12p70 production and increased allogeneic T-cell proliferation compared to cells of normal subjects cultured in normal sera. Monocyte derived dendritic cells of hemodialysis patients cultured in either normal or uremic sera were functionally impaired for endocytosis and maturation but had enhanced IL-12p70 production and allogeneic T-cell proliferation only when cultured with uremic sera. High concentrations of urea in normal sera inhibited all aspects of normal dendritic cell function in vitro. Our study suggests that hemodialysis regimes tailored to remove uremic toxins more efficiently may improve immune functions of these patients

The Relationship Between Health Policies, Medical Technology Trends and Outcomes: A Perspective from the TECH Global Research Network

International audienceThe goal of this paper is to present new comparative evidence on heart attack care in 17 countries showing that changes in medical treatments are universal, but have differed greatly. We have collected a large body of comparable information that show how countries differ in treatment rates and why these differences are relatively marked. Countries appear to differ systematically in the time at which intensive cardiac procedures began to be widely used and in the rate of growth of the procedures. Our results show that differences in treatment rates are greatest for expensive medical technologies. Also strict financing limits and regulatory policies have affected the adoption of intensive technologies. These differences may have important economic and health consequences

Technological Change Around The World: Evidence From Heart Attack Care

International audience"Supply side" incentives to curtail health care spending are closely linked with trends in the use of costly treatments. by the Technological Change in Health Care (TECH) Research Network ABSTRACT: Although technological change is a hallmark of health care worldwide , relatively little evidence exists on whether changes in health care differ across the very different health care systems of developed countries. We present new comparative evidence on heart attack care in seventeen countries showing that technological change-changes in medical treatments that affect the quality and cost of care-is universal but has differed greatly around the world. Differences in treatment rates are greatest for costly medical technologies , where strict financing limits and other policies to restrict adoption of intensive technologies have been associated with divergences in medical practices over time. Countries appear to differ systematically in the time at which intensive cardiac procedures began to be widely used and in the rate of growth of the procedures. The differences appear to be related to economic and regulatory incentives of the health care systems and may have important economic and health consequences. H ea lt h c ar e is an i ndu st ry that is becoming part of a global economy. Biomedical knowledge and technologies are already "global" in the sense that leading physicians in all developed countries read the same journals and electronic reviews and participate in international consortia to encourage best practices. For the most part, the same drugs and devices are available worldwide, at least within a few years of each other. Leading clinical researchers and experts collaborate internationally; leading drug and biotechnology firms think globally. As worldwide policy interest in quality of care continues to rise, international comparisons of health care systems are becoming common. Yet health care also remains a local industry, with care delivered by physicians influenced by their local peers, practice settings, and health care policies