Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]

BACKGROUND: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. METHODS: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. CONCLUSION: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD

Effect of Haemodiafiltration Vs Conventional Haemodialysis on Growth and Cardiovascular Outcomes in Children - The Hdf, Heart and Height (3H) Study

Background: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population. Methods: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m(2); this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 038). Discussion: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD.WoSScopu

Superantigen activation of CD4+ and CD8+ T cells from HIV-infected subjects: role of costimulatory molecules and antigen-presenting cells (APC)

T cell receptor (TCR) triggering via superantigens induces decreased proliferative responses and increased apoptosis in T cells from HIV-infected patients compared with controls. Our aim was to delineate the role of intrinsic T cell defects, of APC dysfunction and of cytokines and costimulatory signal dysregulation in the deficient responses of CD4+and CD8+ T cells from HIV+ subjects to the superantigen Staphylococcus enterotoxin A (SEA). Proliferation and IL-2Rα up-regulation on SEA-stimulated CD4+and CD8+T cells in whole blood were reduced in HIV+ subjects with CD4 counts < 500, compared with controls. Neither addition of IL-2, IL-12 or phorbol myristate acetate (PMA) nor neutralization of endogenous IL-10, tumour necrosis factor-alpha (TNF-α), TNF-β or transforming growth factor-beta (TGF-β) could restore the decreased activation by SEA. Possible intrinsic T cell defects were studied by presenting SEA on HLA-DR-transfected Chinese hamster ovary (CHO) cells, co-expressing LFA3 and/or CD80, to purified T cells. In this system CD8+T cells from most HIV+ patients were hyporesponsive with regard to IL-2 production, IL-2Rα up-regulation and proliferation, whereas clearly reduced responses were only shown in CD4+T cells from AIDS patients. Similarly, apoptosis was increased in CD8+T cells from all patients, but only in CD4+T cells from AIDS patients. During HIV infection, the responses to TCR triggering through SEA are deficient in both T cell subsets. The intrinsic defect appears earlier during disease progression in purified CD8+T than in CD4+T cells, it occurs in conjunction with both CD2 and CD28 costimulation, and it is correlated with increased levels of apoptosis