Vitamin D status and inflammatory markers in Chronic Kidney Disease

Abstract

ABSTRACT

Vitamin D status and inflammatory markers in chronic kidney disease

Yeon Joo Lee Academic advisor: Professor Sang Sun Lee Dept. of Food & Nutrition The Graduate School of Hanyang University

The prevalence of chronic kidney disease (CKD) is growing around the world with an increase in obesity, and a major risk factor for CKD has been suggested as diabetes and hypertension. It should be considered the treatment of the cause of diseases for the management of CKD. The appropriate treatment for the underlying disease is to be accompanied, also the treatment for CKD should be considered that delaying the loss of renal function, delaying the time of dialysis, and preventing the progress of complication such as cardiovascular disease. Recently, vitamin D deficiency in patients with CKD has been reported to increase the risk of cardiovascular disease and mortality in these patients, therefore serum vitamin D level has been suggested as an important predictor in these patients. However, vitamin D deficiency is common in all stages of CKD, especially in hemodialysis (HD) patients. A recent study on CKD patients in Korea showed that hypovitaminosis D is prevalent even in early stages of CKD, and prevalence of vitamin D deficiency increases up to 92.8% in stage 5 CKD [eGFR<15 (ml/min/1,73 m2)] in the winter. Vitamin D is an essential nutrient due to both its classical effects on the skeletal system as well as its extra-skeletal benefits, which include lowered blood pressure, reduction of inflammatory biomarkers, improved insulin sensitivity, and elevated immune function via regulation of innate and adaptive immunity. Moreover, higher levels of circulating 25(OH)D are associated with lower mortality risk in CKD patients. In this regard, guidelines for management of CKD-related bone and mineral disorders should emphasize treatment of hypovitaminosis D. National Kidney Foundation guidelines state that optimal 25(OH)D levels are higher than 30 ng/mL. Therefore, recent studies have investigated the effects of dietary vitamin D intake and sun exposure or cholecalciferol (vitamin D3) supplementation on serum 25(OH)D levels. This study was composed of three parts. The study identified main determinants of serum vitamin D status, evaluated the seasonal variation of 25(OH)D and inflammatory markers, and carried out to investigate the relationship between vitamin D status and inflammatory markers of chronic kidney disease patients.

Part I: Effects of sun exposure and dietary vitamin D intake on serum 25-hydroxyvitamin D status in Hemodialysis patients. A cross-sectional study of 47 HD patients (19 males and 28 females) was performed. We assessed serum 25(OH)D and 1,25(OH)2D levels between August and September 2012 and analyzed the prevalence of vitamin D deficiency in HD patients. To evaluate the determinants of serum 25(OH)D levels, we surveyed dietary vitamin D intake, degree of sun exposure, and outdoor activities. To compare biological variables, serum 25(OH)D was stratified as below 15 ng/mL or above 15 ng/mL. Mean 25(OH)D and 1,25(OH)2D levels were 13.5 ± 5.8 ng/mL and 20.6 ± 11.8 pg/mL, respectively. The proportions of serum 25(OH)D deficiency (<15 ng/mL), insufficiency (15-<30 ng/mL), and sufficiency (≥30 ng/mL) in subjects were 72.4%, 23.4%, and 4.3%, respectively. Prevalence of vitamin D deficiency in female patients was 78.6%, whereas that in males was 63.2% (p=0.046). Vitamin D intake and sun exposure time were not significantly different between the two stratified serum 25(OH)D levels. Dietary intake of vitamin D did not contribute to increased serum 25(OH)D levels in HD patients. The main effective factors affecting serum 25(OH)D status were found to be the exposure and active outdoor exercise. Hypovitaminosis D is common in HD patients and is higher in females than in males. Sun exposure is the most important determinant of serum 25(OH)D status.

Part II: Seasonal variation in vitamin D status and inflammatory markers in Hemodialysis patients This study was a one-year longitudinal observational study. Serum vitamin D levels were evaluated in 39 HD patients at the end of fall (October-November), winter (January-February), spring (April-May), and summer (July-August). To evaluate the association of seasonal variation in vitamin D status and inflammatory markers, the subjects were divided into a responsive group which had increments in serum 25(OH)D above (+) 5 ng/mL, and a non-responsive group which had increments below (+) 5 ng/mL. The 25(OH)D and 1,25(OH)2D levels were significantly lower in spring compared to fall and summer (p<0.001, and p=0.002, respectively). The prevalence of vitamin D deficiency, was increased to 48.7% in spring and decreased to 23.1% in summer. Serum hsCRP levels were significantly higher in summer compared to winter (p=0.041). The adiponectin level, an anti-inflammatory marker, was also significantly higher in summer compared to winter (p=0.034). The proportion of diabetes was significantly higher in the non-responsive group (40%) compared to the responsive group (7%) (p=0.029). Vitamin D deficiency was highly prevalent in HD patients with a marked seasonal variation. The levels of hsCRP were increased in the summer, and other inflammatory markers were higher in this population with DM compared with non-DM.

Part III: Cholecalciferol supplementation on serum inflammatory markers in chronic kidney disease patients with hypovitaminosis D This study was a six - month randomized controlled trial for pre-dialysis CKD patients with hypovitaminosis D (25(OH)D<30 ng/mL). The study subjects (n=92) were stratified three groups according to gender, CKD stage and serum 25(OH)D status. They were randomly allocated to control group (Control) and cholecalciferol supplement group (Group 1). Patients with serum 25(OH)D levels < 10 ng/mL were placed in another cholecalciferol supplement group (Group 2). Randomized patients in the treatment group were instructed to take 2000 IU cholecalciferol per day for 6 months. At baseline and at the end of 6 months, we collected the laboratory parameters from the medical record. We also assessed serum levels of inflammatory markers such as e-selectin, VEGF, and adiponetin at baseline and the end of 6 months to investigate the association between serum levels of 25(OH)D, inflammatory cytokines and other biochemical parameters of control and treatment group. There was a significant increase in 25(OH)D levels at 6 months when compared to baseline. The proportion of adequate vitamin D status (25(OH)D≥30 ng/mL)was 74.3% in Group 1, and was 48.0% in Group 2 at 6 months. Moreover, none of the cholecalciferol treated patients had hypovitaminosis D at 6 months. Cholecalciferol supplementation for 6 months had no significant impact on circulating inflammatory markers related to cardiovascular disease. The present study suggests that hypovitaminosis D with CKD patients can be corrected by taking daily 2000 IU cholecalciferol for 6 months. This replenishment is associated with lowering PTH and ALP levels. However, we were not able to show the effects of cholecalciferol supplementation on the inflammatory markers.