Optimal Vitamin D levels in Children with Chronic Kidney Disease

Abstract

Introduction The vitamin D is an essential factor for skeletal development, and its deficiency can cause growth retardation and skeletal deformities such as rickets [1,2]. Vitamin D 3 (cholecalciferol) sourced from diet and ultraviolet B sunlight is metabolized to 25(OH) vitamin D (25(OH)D, calcidiol) in the liver, and then in the kidney to 1,25(OH) 2 vitamin D (1,25(OH) 2 D, calcitriol) which is the biologically active form [1,2]. Additionally, non-renal production of 1,25(OH) 2 D in skin, colon, prostate, macrophage, and parathyroid has been reported [2]. Calcitriol binds to vitamin D receptor (VDR) within the cells, and acts in intestine, bone, immune cells, and tumor microenvironment [2-4]. The VDR has been reported to be found in endocrine glands, cardiovascular tissues, and hematopoietic cells, and vitamin D has been supposed to be involved to both skeletal disease and nonskeletal diseases including metabolic syndrome, insulin resistance, obesity, cardiovascular diseases, infection, allergy, and cancer [2-5]. Among the various forms of vitamin D in body, serum 25(OH) D is used as a parameter to reflect vitamin D status because 25(OH) D can activate VDR and contribute to the overall vitamin D effect on the target organs [2,3]. Although vitamin D deficiency or insufficiency has been emerging as an important health problem in all age groups, no consensus on the definition of vitamin D deficiency in children exists. Usually, the stratifications according to serum 25(OH)D levels (vitamin D deficiency, <20.0 ng/mL; insufficiency, 20.0-29.9 ng/mL; and sufficiency, ≥30.0 ng/mL) has been used. Vitamin D deficiency or insufficiency is known to be an epidemic of all age populations in many countries, and the main risk factors in pediatric population have been known to include winter season, insufficient outdoor activity, non-white ethnicity, older age, puberty, obesity, female, and low socioeconomic status. Although epidemiologic data on the prevalence of vitamin D deficiency or insufficiency in patients with chronic kidney disease (CKD) are little and sparse, they has been reported to show relatively low levels of 25(OH)D because of low levels of vitamin D-binding protein, little sunlight exposure, malnutrition, dietary restriction, and inadequate ultraviolet B-mediated synthesis of vitamin D in skin [6-8]. In patients with early CKD, dialysis and kidney transplantation, the prevalence of vitamin D insufficiency and deficiency has been reported to be high, and it is also reported that vitamin D deficiency is more common and severe in dialysis patients than in those with early CKD [8]. In CKD patients, bone disorders, hypertension and cardiovascular morbidity seem to be related to vitamin D deficiency [9,10]. It was reported that serum levels of 25(OH)D were also inversely associated with serum level of parathyroid hormone (PTH) in patients with CKD [10]. Therefore, the Kidney Disease Outcomes Quality Initiative (K/ DOQI) clinical practice guidelines for bone mineral metabolism and disease in CKD recommend the measurements of 25(OH)D levels once annually in patients with CKD and supplementation with vitamin D if serum calcidiol level is less than 30 ng/mL [11]. Kidney Disease: Improving Global Outcome (KDIGO) clinical practice guidelines also recommend to check serum 25(OH)D level and correct vitamin D deficiency [12]. However, there is no data how much amount of vitamin D supplementation is necessary for Korean pediatric patients with CKD to maintain the sufficient levels of vitamin D and prevent the vitamin D associated morbidity. Most studies for the prevalence, risk factors, or the morbidity of vitamin D deficiency in CKD patients were conducted in adults patients, and lack of data about serum 25(OH)D levels in pediatric patients with CKD have been reported. Additionally, there is no consensus for Abstract Background: Vitamin D is an essential component of skeletal development. Although hypovitaminosis D has been widely observed, little data for vitamin D status in pediatric patients with chronic kidney disease (CKD) has been reported. The aim of this study was to assess the prevalence of abnormal vitamin D status and analyze factors associated with inadequate 25(OH) vitamin D (25(OH)D) levels in children with CKD.