Background. Cytomegalovirus seropositivity is associated with an increased risk for cardiovascular disease in end-stage renal disease (ESRD) patients. Circulating proinflammatory CD4posCD28null T cells are expanded in cytomegalovirus-seropositive ESRD patients and potentially could mediate atherosclerotic plaque instability and rupture. Methods. In this study, we tested the hypothesis that increased numbers of circulating CD4posCD28null T cells may represent a risk factor for cardiovascular disease in ESRD patients. Prospectively collected data from 240 cytomegalovirus- seropositive stable ESRD patients were analysed. Results. Traditional cardiovascular risk factors (age, smoking, hypercholesterolaemia and diabetes mellitus) and the percentage and absolute number of CD4posCD28null T cells were significantly associated with the presence of atherosclerotic disease, after univariate and multivariate statistical analysis. An ̃2-3-fold increase in the prevalence of atherosclerotic disease was noted between patients with the highest and lowest number of CD4posCD28null cells. CD8posCD28null T-cell populationswere also significantly expanded in cytomegalovirus-seropositive ESRD patients and closely correlated with the number of CD4posCD28- null T cells. However, this cell population was not related to an increased prevalence of cardiovascular disease. Conclusions. Cytomegalovirus-seropositive ESRD patients may have substantially increased numbers of circulating pro-inflammatory CD4posCD28null T cells that are independently associated with the presence of atherosclerotic disease. The expansion of these cells may therefore represent a novel non-traditional cardiovascular risk factor for ESRD patients.

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Nephrology, Dialysis, Transplantation
Department of Internal Medicine

Betjes, M., de Wit, E., Weimar, W., & Litjens, N. (2010). Circulating pro-inflammatory CD4posCD28null T cells are independently associated with cardiovascular disease in ESRD patients. Nephrology, Dialysis, Transplantation, 25(11), 3640–3646. doi:10.1093/ndt/gfq203