## 3 Vitamin D and CKD in Pediatric Patients  
Vitamin D deficiency in CKD is extremely common, both in adults and children. In fact, a significant association between the reduction in glomerular filtration rate and vitamin D deficiency has been widely demonstrated in children [33; 34]. Vitamin D is a pro-hormone essential for human life, mainly involved in calcium-phosphorus metabolism. Vitamin D exists in two main forms: ergocalciferol (vitamin D2), which is mainly found in food sources (such as mushrooms, oily fish, egg yolk and offal), and cholecalciferol (vitamin D3), which is produced in the skin by an endogenous photochemical reaction starting from 7-dehydrocholesterol. Vitamin D, still inactive, initially reaches the liver, where it undergoes a hydroxylation at the carbon 25 position, by 25-hydroxylase, to become 25-hydroxyvitamin D. Finally, it is transported to the kidney, where it undergoes a second hydroxylation, by 1\(\alpha\)-hydroxylase, which converts it to the active form, 1,25-dihydroxyvitamin D [35]. Many studies suggest that CKD patients are at high risk of developing vitamin D deficiency for various causes, even in the early stages of the disease. First of all, vitamin D deficiency in CKD patients can be induced by reducing food intake due to a lack of appetite, a depressive state, dietary restrictions and gastrointestinal alterations that alter the absorption of dietary vitamin D [36]. Furthermore, proteinuria has been described as one of the main factors influencing vitamin D levels in CKD patients. In fact, it has been shown that patients with proteinuria showed significantly lower vitamin D values due to its increased urinary excretion of the vitamin D-binding protein. This protein is responsible for transporting 25-hydroxyvitamin D to the proximal tubule to undergo its activation by the kidney, causing a reduction in active vitamin D levels [37]. Moreover, a reduction in renal mass limits the amount of 1\(\alpha\)-hydroxylase available for the production of active vitamin D. The progressive reduction in glomerular filtration rate (GFR) can also limit the availability of 25(OH)D to 1\(\alpha\)-hydroxylase, causing a reduction in the production of active vitamin D [38]. Another factor that can induce vitamin D deficiency in CKD patients is the rise in FGF23 serum levels that increases with the decline of GFR, which directly suppresses the activity of 1\(\alpha\)-hydroxylase [17]. Finally, uremia, which occurs in the CKD terminal stages, may alter the physiological response of the skin to UVB radiation, which is essential for the production of vitamin D [39]. Vitamin D's main function is to regulate calcium-phosphorus metabolism. In particular, vitamin D stimulates the intestinal absorption of calcium and phosphorus, stimulates the mobilization of calcium in the bones and increases the renal reabsorption of calcium in the distal tubule [40]. Moreover, vitamin D is essential for numerous biological processes and is not only related to the skeletal system. In fact, a vitamin D deficiency not only alters the skeletal processes but also endothelial function, renin-angiotensin-aldosterone system (RAAS) regulation, redox balance and immune system activity [35]. For all these fundamental functions, a deficiency can cause serious damage, especially in the pediatric population. Vitamin D deficiency is one of the most common causes of rickets in children. Ricketts is a condition that can be described as a defect in the mineralization of the epiphyseal plates, which are the growth plates at the ends of the bones. It can manifest itself through irritability, a retardation of the child's growth or, in the most severe cases, with a sudden death [41]. Due to its enormous importance in calcium-phosphorus metabolism, a long-term deficiency of vitamin D can cause a reduction in serum calcium levels, causing an inhibition of the bone mineralization process, essential for the skeletal growth of the child [42,43].