## 3 Vitamin D and CKD in Pediatric Patients
### Dental caries in CKD pediatric patients
According to the study by [PERSON] et al., conducted on CKD children (aged 4-13.6), the mean salivary urea level was significantly higher (11.6 mmol/L) compared to the healthy controls (3.6 mmol/L); a significant difference was also highlighted between the buffering capacity (pH 6.4) compared to the healthy controls (pH 5.6) [66]. Moreover, in a case-control study conducted on hemodialysis pediatric patients (aged 4-17), it was observed that 89.5% of them showed a high salivary buffer capacity [129]. The alkaline salivary pH determines the acids neutralization and protects the tooth from demineralization [130]. In fact, the tooth surfaces are continuously subjected to acid attack from organic acids formed by the bacterial fermentation of refined carbohydrates [112] or by an excessive consumption of acidic beverages and foods [131]. * Oral microbiota. The alkaline salivary pH creates an unfavorable environment for acidogenic cariogenic bacteria and ecological shift, modifying the salivary microbiota to non-cariogenic bacterial species [48]. In a study conducted on hemodialysis patients (aged 4-17), the salivary levels of _Streptococcus mutans_ and Lactobacillus were significantly lower than in the control group of healthy subjects [129]. The same evidence was highlighted by a further study conducted on hemodalyzed children [84]. On the contrary, in kidney-transplanted patients, a decrease in oral pH is observed, which could modify the oral microbiota and promote the onset of caries pathology, especially in those subjects who have poor eating habits (rich in free sugars) [48]. Furthermore, kidney-transplanted patients may take immunosuppressive drugs (such as cyclosporine A) and antihypertensive calcium-blocking agents, which can determine gingival overgrowth (Drug-Induced Gingival Overgrowth--DIGO) and complicate daily tooth brushing maneuvers for the removal of dental plaque [132]. In a recent study, it was found that 16.7% of pediatric subjects undergoing kidney transplant had DIGO, especially grade 1 [67]. Natural Bioactive Compounds as Innovative Tools in the Prevention and Adjuvant Treatment of Remineralization and Dental Caries in CKD Pediatric Patients  
In CKD pediatric patients, DDEs and dental caries can be treated with traditional therapies adapted to children; however, for their prevention, an important role can be played by natural bioactive compounds (NBCs) derived from plant-based foods [133]. These innovative treatments, although they do not replace standard treatments, can represent a valid adjuvant therapy in the prevention of dental caries especially. NBCs are described as organic compounds of various origins (mainly from plant-based foods) and with different chemical structures, which exert important actions at the level of biological tissues. They can be classified via their chemical structure and their biological activity through the following molecules: phenols, carotenoids, alkaloids, phytosterols, nitrogen compounds and organosulfur compounds [134; 135]. These molecules exert numerous beneficial effects for human health and several clinical studies have highlighted how they could play a pivotal role in the treatment of the DDEs and in dental caries prevention. Some literature studies pointed out how tannins and phenolic compounds, contained in numerous herbaceous plants, would seem to stimulate, through a wide variety of mechanisms of action (such as the suppression of ATP synthesis or energy metabolism), the re-mineralization of dental enamel, both in adults and in children [136; 137; 138]. Another study demonstrated that the use of a toothpaste based on theobromise, a purine alkaloid present in cocoa beans, has an important re-mineralizing effect on tooth enamel, comparable to that of a fluoride-based toothpaste [139]. Therefore, the use of plant-based oral hygiene products could be a valid strategy for the treatment of DDEs in CKD children. The main NBCs studied for the dental caries prevention are polyphenols. This class of compounds can act through two main mechanisms.