Transplantation - clinical II

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Introduction and Aims: Endothelial progenitor cells (EPCs) participate in regenerative processes of the vasculature, develop incompetence in several states of disease, and also have prognostic value.The effects of various immunosuppressants on EPCs are unknown. Methods:In an open-label, randomized controlled trial cyclosporine A (CSA) treated kidney transplant recipients (KTRs) with stable graft function were assigned to receive tacrolimus (TAC) at target trough levels of 5-8 ng/mL or to continue CSA based immunosuppression at target trough levels of 70-150 ng/mL at a 2:1 ratio.The primary end-point was the effect of TAC on EPC count at 3, 12, and 24 months after conversion from CSA. Secondary objectives included renal function, humoral alloreactivity, pharmakogenetics, traditional cardiovascular disease risk factors, and safety.EPCs were assessed by whole-blood flow cytometry (CD34+CD133+KDR+), cell culture assay (endothelial cell-colony forming units [EC-CFU] and circulating angiogenic cells [CAC]).Between group comparisons were performed by Mann-Whitney-U test.Friedman tests were used to test for changes within groups over time.Results: 148 patients were randomized and 141 were included into the intent to treat analysis (55.6 [46.5-65.0]years old; 67% male; renal graft vintage 6.2 years [3.2 -12.5], with an estimated glomerular filtration rate of 45.8 [37.9 -57.6] mL/min per 1.73m2).The counts of EPCs, CACs, and EC-CFUs are indicated in Table 1.Conclusions: Our study provides evidence that TAC has no favorable effect on EPCs in stable long-term KTRs.However, the decrease of EPCs over time and the trend for lower EPC counts in TAC treated patients deserves further examination.

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