Vitamin D deficiency, CD4+CD28null cells and accelerated atherosclerosis in chronic kidney disease

Abstract

Aim: Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease (CKD) patients. The role of vitamin D remains controversial in this process. We evaluated the relationship between 25-hydroxyvitamin D, abnormal T helper cells (CD4+CD28null cells), systemic inflammation and atherosclerosis in CKD patients. Methods: A total of 101 stage 4-5 non-dialysis CKD patients and 40 healthy controls were studied. Common carotid artery intima media thickness (CCA-IMT) was measured with an ultrasound system. 25(OH) vitamin D and highly sensitive C-reactive protein (hsCRP) were measured in serum by enzyme linked immunosorbent assay. The frequency of circulating CD4+CD28null cells was evaluated by flowcytometry. Results: CKD subjects exhibited higher CCA-IMT (0.71 ± 0.01 vs 0.56 ± 0.01 mm, P < 0.0001), hsCRP (90.7 ± 5.8 vs 50.1 ± 8.6 μg/mL, P < 0.0001), CD4+CD28null cell frequency (9.1 ± 0.9 vs 3.6 ± 0.5%, P < 0.0001) and lower 25(OH) vitamin D levels (17.9 ± 1.9 vs 26.9 ± 3.5 ng/mL, P < 0.0001). In CKD subjects, serum 25 (OH) vitamin D level showed a strong inverse correlation with CCA-IMT (r = -0.729, P < 0.0001) and correlated with CD4+CD28null cell frequency (r = -0.249, P = 0.01) and hsCRP (r = -0.2, P = 0.047). We also noted correlation of IMT with patient age (r = 0.291, P = 0.004) and CD4+CD28null cells (r = 0.34, P = 0.001). On multiple regression analysis, 25(OH) vitamin D level, diabetic status and CD4+CD28null cell frequency exhibited independent association with IMT in CKD subjects. Conclusions: Vitamin D deficiency, inflammatory activation and higher frequency of CD4+CD28null T lymphocyte population correlate with preclinical atherosclerotic changes in CKD population. These findings suggest possible linkage between vitamin D metabolism and T cell modulation - abnormalities that may contribute to development of atherosclerosis in CKD. The possible links between vitamin D, immune function and atherosclerosis are explored in this paper. Using intima-media thickness as an index of vascular disease, significant associations were found with low levels of vitamin D, hsCRP and the frequency of T lymphocyte subsets. These findings suggest that the link between vitamin D and vascular disease in chronic renal failure might involve the immune system. © 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.