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

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.