Increase in CD8+CD158a+ T Cells in Kidney Graft Blood is Associated with Better Renal Function.

BACKGROUND Studies of liver and heart transplant patients have shown a gradual reconstruction of the CD8 KIR2D+ T cell subpopulations, measured in peripheral blood (PB), associated with better graft acceptance. The kinetics of these populations in kidney transplants, however, is still poorly understood, especially given the lack of studies of blood samples from the kidney graft. MATERIAL AND METHODS Flow cytometry was used to measure CD8+CD158a/b/e T cells in 69 kidney transplant patients who had stable renal function during follow-up. Measurements were made at 3, 6, and 12 months post-transplantation in graft capillary blood extracted by fine needle aspiration puncture (FNAP) and in PB. RESULTS No progressive increase was found in the PB subpopulations. However, the CD8+CD158a+ subsets increased significantly at 12 months in the graft blood versus the PB samples (3.91±4.59 vs. 2.84±4.71; p=0.021). The ratio of the percentage of CD8+CD158a+ cells in graft blood compared to PB at 12 months was associated with better renal function in those patients with a ratio ≥3 (66.6±14.53 vs. 55.7±21.6; p=0.032). CONCLUSIONS An increased ratio of CD8+CD158a+ cells, measured by flow cytometry, between graft blood and PB was associated with improved renal function.

Peripheral Vascular Disease and Death in Southern European Kidney Transplant Candidates: A Competing Risk Modeling Approach.

BACKGROUND: The association between peripheral vascular disease (PVD) and survival among kidney transplant (KT) candidates is uncertain. METHODS: We assessed 3851 adult KT candidates from the Andalusian Registry between 1984 and 2012. Whereas 1975 patients received a KT and were censored, 1876 were on the waiting list at any time. Overall median waitlist time was 21.2 months (interquartile range, 11-37.4). We assessed the association between PVD and mortality in waitlisted patients using a multivariate Cox regression model, with a competing risk approach as a sensitivity analysis. RESULTS: Peripheral vascular disease existed in 308 KT candidates at waitlist entry. The prevalence of PVD among nondiabetic and diabetic patients was 4.5% and 25.3% (P < 0.0001). All-cause mortality was higher in candidates with PVD (45% vs 21%; P < 0.0001). Among patients on the waiting list (n = 1876) who died (n = 446; 24%), 272 (61%) died within 2 years after listing. Cumulative incidence of all-cause mortality at 2 years in patients with and without PVD was 23% and 6.4%, respectively (P < 0.0001); similar differences were observed in patients with and without diabetes. By competing risk models, PVD was associated with a 1.9-fold increased risk of mortality (95% confidence interval [95% CI], 1.4-2.5). This association was stronger in waitlisted patients without cardiac disease (subhazard ratio, 2.2; 95% CI, 1.6-3.1) versus those with cardiac disorders (subhazard ratio, 1.5; 95% CI, 0.9-2.5). No other significant interactions were observed. Similar results were seen after excluding diabetics. CONCLUSIONS: Peripheral vascular disease is a strong predictor of mortality in KT candidates. Identification of PVD at list entry may contribute to optimize targeted therapeutic interventions and help prioritize high-risk KT candidates.

Decrease in the percentage of peripheral blood CXCR3highCD4+ lymphocytes after renal transplantation.

INTRODUCTION: Previous studies suggest that infiltration into the graft of active T cells following kidney transplantation depends on the expression of chemokines and their interaction with their T-cell receptors. However, little is known about the natural history of the expression of these molecules during the early post-transplantation phase. AIM: To evaluate the percentage of CXCR3highCD4+ and CCR4highCD4+ cells, as markers of the Th1 and Th2 populations, in peripheral blood from uremic patients before transplantation and six months after maintaining an acceptable kidney graft function. MATERIAL AND METHODS: Flow cytometry was used to measure CXCR3highCD4+ and CCR4highCD4+ cells from 44 consecutive patients who received a kidney transplant at our center. Measurements were made at the time of transplantation and six months later. RESULTS: There was a significant reduction after transplantation in the CXCR3highCD4+/CCR4highCD4+ balance (10.68±20.28 vs. 2.01±3.15, p=0.001). Separate analysis of each subset showed a significant reduction after transplantation in CXCR3highCD4+ (2.37±2.75 vs. 1.49±2.66, p=0.010) but no difference in CCR4highCD4+ (0.83±1.01 vs. 1.01±1.12, p=0.812). CONCLUSION: Prior to kidney transplantation uremic patients have an immunologic activation with Th1 polarization (studied by analyzing the CXCR3highCD4+ and CCR4highCD4+ populations) that falls after transplantation. This can be monitored with the CXCR3highCD4+ lymphocyte subset. This may help understand the pathologic mechanisms intervening in immunologic dysfunction of kidney grafts.