Abstract

Abstract BACKGROUND AND AIMS Cardiovascular disease (CVD) and chronic kidney disease (CKD) are closely interrelated. Adverse immune responses have been implicated in the pathogenesis of both CVD and CKD [1, 2]. Monocyte subsets are key in atherogenesis and the inflammatory cascade occurring in heart failure [1, 2]. Likewise, the role of lymphocyte subpopulations including natural killer (NK) cells and CD4 + CD25 + regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention [2]. The implication of immune cells subsets in the abnormal myocardial remodeling as universally occurs in CKD patients even without overt CVD, remains to be clarified [3]. The aim of our study was to investigate potential correlations between blood levels of specific immune cells subsets with conventional and novel deformation-related indices of LV function in a cohort of patients with CKD without established CVD. METHOD A total of 35 stable CKD patients (mean age 66 ±12.2 years, 57% males, 20% diabetics) without established CVD were included in the study. Exclusion criteria included the history of malignancy, autoimmune disease and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16 + and CD14 + CD16++ percentage and absolute number of cells out of the total monocytes and NK cells (CD3 + CD16 + 56+), CD3-CD19 + B lymphocytes, CD3 + CD4 + T cells, CD3 + CD8 + T cells and Tregs (CD4 + CD25 + FoxP3+) absolute values and percentage out of the total lymphocytes were measured by flow cytometry. Simultaneously, conventional [left atrial volume index (LAVI), LV mass index (LVMI), LV end-diastolic volume (LVEDV), E/E’] and novel 2D speckle tracking (2DST) echocardiographic indices of LV function [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), TWIST and UNTWIST] were assessed. RESULTS The mean estimated glomerular filtration rate (eGFR) was 28 ±15 mL/min/1.73 m2 (CKD-EPI) and the mean 24-h proteinuria was 2457 ±2399 mg. The percentage of total blood lymphocytes, as well as both percentage and absolute counts of CD4 + T-cells, were positively correlated with the eGFR (P < 0.05 and < 0.01 respectively) whereas. In addition, both NK cells percentage (P < 0.05) and absolute values (P < 0.01) showed a negative association with proteinuria. Regarding classical indices of LV function, NK counts were negatively associated with LVEDV (P < 0.05). An increased percentage of intermediate CD14++CD16 + monocytes was positively associated with the GRS (P < 0.005). Furthermore, the percentage of T-cells and CD8 + T-cells were positively associated with LV TWIST whereas a positive association was found between the percentage of CD8 + T-cells and more negative values of LV UNTWIST (P < 0.05). No specific significant correlations were observed between the rest immune cells subpopulations with either the classical or the novel indices of LV dysfunction. CONCLUSION The results of our study suggest that alterations of immune cells subsets correlate with subclinical markers of LV dysfunction in CKD patients without established CVD. The significance of the implication of the cellular arm of the immune system in the pathophysiological pathways of specific CVD phenotypes in CKD and the utility of immune cells subsets as tools to identify CKD patients who are at the highest risk for developing complications shall be elucidated by future research.

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