title: Vitamin D deficiency, CD4+CD28null cells and accelerated atherosclerosis in chronic kidney disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Yadav
authors.forename: Debasish
authors.initials: D
authors.lastname: Banerjee
authors.forename: Anupam
authors.initials: A
authors.lastname: Lal
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000276:immunology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000276:immunology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000276:immunology; D018570:Risk Assessment; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications* / Q000276:immunology
chemical_list: D015415:Biomarkers; D018106:CD28 Antigens; D014807:Vitamin D; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D