## 3 Vitamin D and CKD in Pediatric Patients
### Dental caries in CKD pediatric patients
A diet characterized by a controlled protein intake and a high caloric intake derived from carbohydrate, that is recommended for CKD conservative patients, could be another risk factor for caries disease [50; 114], whereas in hemodialysis patients the nutritional-dietetic treatment is characterized by a high protein intake (1.1-1.2 g/kg of ideal body weight/day) and a normal-high caloric intake (30-35 kcal/kg of ideal body weight/day) [115; 116]. In this regard, a study conducted on CKD patients undergoing hemodialysis highlighted how a higher sugar intake, more frequent in CKD patients than healthy controls, was associated with an altered oral microbiota (characterized by an increase in the supragingival plaque samples of _Streptococcus mutans_, _Lactobacillus salivarius_, _Lactobacillus fermentumum_, _Lactobacillus vaginalis_, _Scardovia vigossiae F0424_ and _Actinomyces naslundii_) and a higher DMFT [101]. * DDEs. The DDEs are risk factors for the development of curious lesions [91]. Enamel defects with their rough and irregular surfaces can promote the accumulation of plaque and the determination of a cariogenic bacterial ecological niche [117]. Furthermore, teeth with DDEs have a lower enamel hardness and are subject to wear, especially when the thin enamel layer is subjected to masticatory loads [48]. Moreover, they are shown to have a lower resistance to acid insult when compared to healthy enamel [81]. On the contrary, CKD patients show a lower percentage of dental caries despite having a high prevalence of DDEs compared to healthy subjects [62]. This observation could be explained by analyzing the protective factors of dental caries in CKD subjects. * Uremic gastritis. CKD patients, especially in more advanced stages, are often characterized by a condition known as uremic gastritis, that among the possible consequences, may induce gastroesophageal reflux and vomiting. These manifestations can lead to enamel erosion, with a consequent increased risk of dental caries [118]. * Vitamin D Deficiency. Several cross-sectional studies state that vitamin D deficiency is associated with an increased incidence of dental caries in the primary dentition [117,119] and in permanent dentition [120,121]. Moreover, the recent systematic reviews point out a relationship between low serum vitamin D levels and dental caries in children and adolescents in primary dentition [122] and in permanent dentition [123]. In a study by [PERSON] and [PERSON] [113], several mechanisms are proposed to explain this relationship: (1) the alteration of enamel mineralization with consequent presence of DDEs, which constitute a risk factor for dental caries (as described above); (2) the reduced activation of antimicrobial (AMPs) peptides, such as cathelicidins and defensins, which have antimicrobial properties against several bacteria and participate in the innate immune response [74,124,125,126]; (3) decreased saliva flow and the alteration of its composition by reducing the amount of calcium ions. As previously mentioned, numerous studies underline how CKD could also represent a protective factor for caries development. These factors in CKD patients are as follows: increased salivary buffering capacity, alkaline salivary pH, and the modification of salivary microbiota. * Buffer system and salivary pH. In CKD patients, an increased buffering capacity of saliva and an alkaline salivary pH are observed, probably due to the higher concentration of ammonia obtained from the urea hydrolyzation in the mouth through bacterial ureases [84,127]. In fact, the qualitative composition of saliva in CKD patients tends to change compared to healthy subjects; namely, it is characterized by a higher concentration of urea, creatinine, sodium, potassium, chloride and phosphorus [128]. [PERSON] et al. also report that the salivary levels of urea and the IgA anti-Streptococcus mutans are higher in CKD patients (especially in chronic maintained hemodialysis patients) than in the healthy group and it may be a protective factor against dental caries [83].