FP133DISTURBANCES OF T CELL POPULATIONS, CD4CD28NULL, NATURAL KILLER CELLS AND TREGS IN CHRONIC KIDNEY DISEASE

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INTRODUCTION AND AIMS: Chronic Kidney injury (CKD) is associated with an increased prevalence of accelerated atherosclerosis and infections, which usually result because of chronic inflammation and aberrations in the integrity of immune reactions. Alterations in both the innate and adaptive immune system have been described in patients on chronic hemodialysis, although whether those changes are present on pre-dialysis stages or develop after initiation of renal replacement therapy has not yet been identified. The aim of the present study was to assess changes in the T cell repertoire within CKD patients on pre-dialysis state. METHODS: T cells subpopulations, namely CD3+CD4+, CD3+CD8+, Natural Killer cells (CD4+CD16+56+), Tregs (FoxP3+CD4+) and CD4+CD28- cells, were isolated from whole blood samples using flow cytometry in 21 predialysis CKD patients (stage V CKD) and the results were compared to age and gender matched healthy controls. RESULTS: Patients with CKD had reduced total lymphocyte number (1497±717μ/L vs. 2062±512μ/L, p=0.03) and percentage (19±5.6% vs. 30.7±10%, p=0.01). Furthermore the total number and frequency of CD4+Tcells of CKD patients was significantly decreased (685±389μ/L vs. 1076±-336μ/L, p<0.01 and 46±-9% vs. 52±7%, p<0.05, respectively), while the percentage of CD8+ (29±10% vs. 23±7%) was increased comparing to healthy controls, leading to a reduction of the CD4/CD8 ratio (1.8±0.9 vs 2.4±1.1). Increased frequencies of NK cells (16.2±7.3% vs. 13.8±5.1%) and CD4+CD28- cells (9.4±10.1% vs. 4.9±2.06%, p<0.05), increased total numbers of CD4+CD28- cells (71.1±116μ/L vs. 48.3±17μ/L) and marked reduction of frequencies and total numbers of Tregs (49.5±26μ/L vs. 62.2±24μ/L) although their frequencies were slightly higher (7.6±2.2% vs 6.2±2.1%) compared to healthy controls. In four patients who had a follow up sample 6 months after starting on renal replacement treatment, a further increase in CD4+CD28- cells (total number 65±92μ/L vs. 34±44μ/L and percentiles 5.8±6.5 vs. 4.5±5%), as well as in NK cells (total number 270±70μ/L vs. 169±25μ/L, p=0.05 and frequencies 15.3±6.7% vs. 11.5±3.3%) was noticed. Interestingly, there was a marked reduction in the Treg cells subpopulation, compared to pre-dialysis CKD patients (total number 35±23μ/L vs. 55±19μ/L, frequencies 3.9±2.4% vs. 7.02±2.2%) CONCLUSIONS: Significant alterations regarding the adaptive immune system within CKD patients were noticed, affecting subpopulations of T cells, with a reduction in CD4+ and Treg cells, and increased expression of NKs and CD4+CD28-cells among CKD patients compared to healthy controls, which were further enhanced after starting on renal replacement treatment. The above changes may be implicated in the development and progression of atherosclerosis, a common finding in patients with CKD.

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