Proinflammatory CD4+ T cells without the costimulatory molecule CD28 (CD4+CD28null T cells) are expanded in patients with end-stage renal disease (ESRD) and associated with atherosclerotic vascular events (AVE). In a prospective study, the number of circulating CD4+CD28null T cells was established in 295 ESRD patients prior to receiving a kidney allograft. Within the first year after transplantation, an AVE occurred in 20 patients. Univariate analysis showed that besides a history of cardiovascular disease (CVDpos, HR 8.1, ), age (HR 1.04, ), dyslipidaemia (HR 8.8, ), and the % of CD4+CD28null T cells (HR 1.04 per % increase, 95% CI 1.00–1.09, ) were significantly associated with the occurrence of a posttransplantation AVE. In a multivariate analysis, only CVDpos remained a significant risk factor with a significant and positive interaction between the terms CVDpos and the % of CD4+CD28null T cells (HR 1.05, 95% CI 1.03–1.11, ). Within the CVDpos group, the incidence of an AVE was 13% in the lowest tertile compared to 25% in the highest tertile of % of CD4+CD28null T cells. In conclusion, the presence of circulating CD4+CD28null T cells is associated with an increased risk for a cardiovascular event shortly after kidney transplantation. 1. Introduction Patients with end-stage renal disease (ESRD) carry a highly increased risk for cardiovascular disease and an increased risk for an acute atherosclerotic vascular event shortly after kidney transplantation [1]. Traditional risk factors like smoking, hypertension, and hypercholesterolaemia can be identified but do not explain the full magnitude of the increment in risk [2–4]. In addition, treatment with statins has not resulted in a decreased cardiovascular mortality in ESRD or kidney transplant patients, indicating that other mechanisms of atherosclerotic disease are important [5–8]. Within the circulating CD4+ T cells population, a subset of cells can be identified that have lost the expression of the costimulatory molecule CD28 on their cell surface. These CD4+CD28null T cells are a rare population in most healthy individuals and usually do not exceed a few percent of the total CD4+ T cell population [9]. However, in patients with end-stage renal disease the numbers of circulating CD4+CD28null T cells may increase considerably and may represent >50% of the total CD4+ T cell population [10]. Phenotypical and functional analysis has identified these cells as highly differentiated proinflammatory T cells with intracellular granule containing cytotoxic molecules like granzyme and perforin [9]. Early
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