Circulating CD4(+)CD28null T Cells May Increase the Risk of an Atherosclerotic Vascular Event Shortly after Kidney Transplantation

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, P < 0.001), age (HR 1.04, P = 0.02), dyslipidaemia (HR 8.8, P = 0.004), and the % of CD4(+)CD28null T cells (HR 1.04 per % increase, 95% CI 1.00-1.09, P = 0.01) 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, P < 0.001). 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.