SP416VITAMIN D3 MODULATES INFLAMMATORY RESPONSE AND EXPRESSION OF VITAMIN D-REGULATORY PROTEINS IN CIRCULATING MONOCYTES OF PATIENTS ON DIALYSIS WITH HYPOVITAMINOSIS D

Abstract

Introduction and Aims: Vitamin D may exert pleiotropic effects on several complications of CKD, such as chronic inflammation which is highly prevalent in patients on dialysis. Although a potential benefit of the vitamin D repletion on inflammation has been suggested, this issue has still been poorly investigated in patients on dialysis. Therefore, in the current study, the effects of cholecalciferol supplementation on inflammatory markers and on vitamin D‐regulatory proteins were investigated. Methods: In this 12‐week double‐blind placebo‐controlled trial, 38 patients with 25 (OH)D<20 ng/mL (23 on hemodialysis and 15 on peritoneal dialysis) were randomized either to the vitamin D3 group (n=20; 50.000 IU of cholecalciferol twice weekly) or to the control group (n=18; 50 drops of a placebo solution twice weekly). Serum levels of 25(OH)D, interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐alpha) and C‐reactive protein (CRP) were measured. The expression of IL‐6, vitamin D receptor (VDR), 1‐alpha hydroxylase and 24‐hydroxylase enzymes in monocytes was determined by flow cytometry. Results: Forty‐seven percent of the patients were men, 42% were diabetics and 89.5% were hypertensive. The mean age was 56+/‐13.4 years, BMI was 25.4+/‐5.6 kg/m2 and the median dialysis vintage was 30.5 (12.5 to 54.5) months. Demographic, clinical, nutritional and laboratory parameters at baseline did not differ between groups. After 12 weeks, serum 25(OH)D increased from 14.3+/‐4.7 ng/mL to 43.1+/‐11.0 ng/mL (p<0.001) in the vitamin D3 group and did not change in the control group (13.9+/‐4.2 ng/mL to 13.5+/‐4.3 ng/mL; p=0.562). Serum IL‐6 and CRP decreased significantly from 8.1+/‐6.6 pg/mL to 4.6+/‐4.1 pg/mL (p=0.012) and from 0.50 (1.00‐1.27) mg/dL to 0.28 (0.09‐0.62) mg/dL ( p=0.010), respectively, only in the vitamin D3 group. Serum TNF‐alpha did not change in both groups. In monocytes, the 1‐alpha hydroxylase enzyme expression and the VDR expression increased in the vitamin D3 group (p=0.019), while in the control group 1‐alpha hydroxylase expression did not change and the VDR expression decreased (p=0.019). There were no changes in the IL‐6 and 24‐hydroxylase enzyme expression in both groups. Conclusions: In conclusion, a high dose of cholecalciferol promoted a decrease of serum inflammatory markers and an increase in the expression of 1‐alpha hydroxylase enzyme and vitamin D receptor in monocytes of dialysis patients with hypovitaminosis D.