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      Potential role of the soluble form of CD40 in deficient immunological function of dialysis patients: new findings of its amelioration using polymethylmethacrylate (PMMA) membrane

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          Abstract

          Even though numerous studies have helped to better delineate abnormalities of either innate or adaptive immune system in end-stage renal disease (ESRD) patients, understanding immune dysfunctions in ESRD patients remains a very complex puzzle with missing pieces. In this context, we showed that the soluble form of CD40 (sCD40) is elevated in ESRD patients and is associated with a lack of response to hepatitis B vaccination. Interestingly, although most dialysis membranes are unable to clear sCD40, we demonstrated that polymethylmethacrylate (PMMA) BK-F membranes (Toray Medical Company, Japan) allow a dramatic diminution of the molecule. We took advantage of this observation to address the question of the potential usefulness of PMMA membrane (BK-F series) in the improvement of humoral immune response of ESRD patients. We, thus, present our recent data highlighting the potential role of BK-F membrane in the improvement of hepatitis B vaccination of ESRD patients who failed to mount a protective immune response despite one or more well-conducted anterior vaccination.

          Taken as a whole, our findings reinforced the concept of seeing dialysis membranes not just as a simple diffusive device but as a tool to tailor dialysis procedure to improve the global quality of life of ESRD patients. This opens a wide area of investigation, notably for the management of immunological dysfunction of ESRD patients.

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          Most cited references39

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          Aspects of immune dysfunction in end-stage renal disease.

          End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area.
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            Cancer in patients on dialysis for end-stage renal disease: an international collaborative study.

            Previous studies have suggested that the frequency of cancer is higher in patients with end-stage renal disease (ESRD) than in the general population, but have not established whether this increase is confined to certain cancers or to certain categories of ESRD patients. The aim of this study was to examine the risk of cancer in a large cohort of patients treated by dialysis but not transplantation. We assembled a cohort of 831,804 patients who received dialysis during the period 1980-94 for ESRD in the USA, Europe, Australia, or New Zealand. We compared the observed frequency of cancer among these patients during 2,045,035 person-years of follow-up with the frequency of cancer in the respective background populations. During average follow-up of 2.5 years, 25,044 (3%) of 831,804 patients developed cancer compared with an expected number of 21,185 (standardised incidence ratio 1.18 [95% CI 1.17-1.20]). We observed a higher risk of cancer in patients younger than 35 years (3.68 [3.39-3.99]), and the risk gradually decreased with increasing age. High risks were observed for cancer of the kidney (3.60 [3.45-3.76]), bladder (1.50 [1.42-1.57]), and thyroid and other endocrine organs (2.28 [2.03-2.54]). Excess cancers appeared in several organs for which viruses have been suspected as causative agents, whereas cancers of the lung, colorectum, prostate, breast, and stomach were not consistently increased. The overall risk of cancer is increased in patients with ESRD, and the distribution of tumour types resembles the pattern seen after transplantation (although we have no data to make the comparison with skin cancer). The excess risk can largely be ascribed to effects of underlying renal or urinary-tract disease, or of loss of renal function, on the kidney and bladder, and to increased susceptibility to viral carcinogenesis. The relative risk, which is especially high in younger patients, gradually diminishes with age.
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              Disturbances of acquired immunity in hemodialysis patients.

              Acquired immunity disturbances in hemodialysis (HD) patients are many and diverse. They are caused by uremia per se, the HD procedure, chronic renal failure complications, and therapeutic interventions for their treatment. Current data suggest that acquired immunity disturbances in HD patients concern mainly the T-lymphocyte and the antigen-presenting cell (APC). The T-lymphocyte-dependent immune response is deficient, predisposing to infections and inadequate response to vaccinations. In addition, APCs are preactivated, which seems to be responsible for the malnutrition-inflammation-atherosclerosis syndrome, and also affects T-lymphocyte function. At the molecular level it is assumed that the interaction between the APC and the T-lymphocyte is impaired. This disturbance is likely to concern the signal that results from the interaction between the major histocompatibility complex:peptide complex on APC surfaces and T-cell receptors on T-lymphocyte surfaces, or the signal that results from the interaction among the co-receptors of these two cells. The aim of the present review was to collect and classify the available clinical and experimental data in this area. Although many pieces are still missing from the puzzle, a better understanding of the responsible molecular mechanisms, will potentially lead to increased survival and a better quality of life in HD patients.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                ndtplus
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                May 2010
                : 3
                : Suppl 1 , Dialysis for High Quality of Life - Complications and Prognosis
                : i20-i27
                Affiliations
                [1 ]UMR–CNRS 5164 CIRID, Université Victor Segalen , Bordeaux, France
                [2 ]Department of Immunology, Pellegrin Hospital , Bordeaux, France
                [3 ]Department of Nephrology, Pellegrin Hospital , Bordeaux, France
                Author notes
                Cécile Contin-Bordes; E-mail: cecile.bordes@ 123456chu-bordeaux.fr
                Article
                sfq033
                10.1093/ndtplus/sfq033
                4392131
                e43d9509-1776-41cf-b021-f956134b5f8a
                © The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 7 December 2009
                : 22 February 2010
                Categories
                Original Article

                Nephrology
                haemodialysis,immune dysfunctions,polymethylmethacrylate (pmma) membrane,hepatitis b vaccination,soluble cd40

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