Association Between Salivary Cytokines, Chemokines and Growth Factors and Salivary Gland Function in Children with Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is a systemic inflammatory disease that leads to multiple organ complications not only in the kidneys and the cardiovascular system, but also in the oral cavity. CKD children experience reduced saliva secretion (hyposalivation), which leads to increased incidence of dental caries and significant impairment of patients' quality of life. However, the causes of salivary gland dysfunction in children with CKD are unknown. The present study is the first to evaluate the inflammatory and anti-inflammatory profile in the saliva of children with CKD at different stages of renal failure with normal and reduced salivary gland function. Methods: Thirty children with CKD (age 9-16) and thirty age-and gender-matched healthy children were classified for the study. Salivary inflammatory and anti-inflammatory profile were assayed using the multiplex ELISA assay. Results: We demonstrated statistically significant changes in salivary pro-inflammatory (↑TNF-α, ↓IL-7), anti-inflammatory (↑IL-10), Th1 (↑INF-γ, ↑IL-15), Th2 (↑IL-4, ↑IL-5, ↑IL-6, ↑IL-9) and Th17 (IL-17) cytokines as well as chemokines (↑MCP-1/CCL-2, ↑MIP-1α/CCL3, ↓MIP-1β/CCL4, ↓EOTAXIN/CCL11) and growth factors (↑G-CSF, ↑FGF) in unstimulated saliva of children with CKD compared to the controls. Although the evaluation of the salivary inflammatory profile does not indicate a particular dominance of any of the branches of the immune system, we observed a statistically significant increase in the concentration of all Th2 cytokines assayed. The multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors depends on the secretory function of the salivary glands, ie, salivary flow, total protein concentration and amylase activity in the saliva. Salivary MIP-1α/CCL3 was the most effective to differentiate children with CKD and hyposalivation from patients with normal saliva secretion. Discussion: Inflammation is involved in salivary gland dysfunction in children with CKD, although further studies on in vitro and in vivo models are necessary to confirm this hypothesis.

Saliva-Based Protein Analysis in Pediatric Dentofacial Inflammation

“…This is consistent with the results of other authors. 8,15,22 Comparing cytokine levels such as IL-5, IL-10, IL-17A, and IL-12p70, which play important roles in regulating the immune response, can help to understand the differences between the inflammatory and tissue regeneration processes. 22 Additionally, Eotaxin, Rantes, VEGF, and IP-10 are chemokines that play a significant role in the chemotaxis and recruitment of different types of cells to sites of infection or inflammation, which can influence the course of the disease.…”

Association of Ischemia-Modified Albumin (IMA) in Saliva, Serum, and Urine with Diagnosis of Chronic Kidney Disease (CKD) in Children: A Case-Control Study

“…Biomolecules can be translocated from the blood to saliva via intracellular (diffusion, filtration, active transport) or extracellular (ultrafiltration, transport across damaged membranes) transport mechanisms. Biomolecules are also produced by the salivary glands [ 36 ]. Interestingly, the salivary glands are highly sensitive to oxidative damage [ 37 ].…”

Oral Manifestations of Children with Chronic Kidney Disease: A Review Article

“…Several causes of xerostomia in CKD have been studied in literature, yet, the definitive cause is still unknown. [36] Postorino et al [37] reported the presence of salivary gland fibrosis and atrophy in ESRF patients which manifested clinically in xerostomia.…”

“…Patients on HD are also advised to limit fluid intake which may contribute to reduced salivary production. [38] Another study by Szulimowska et al [36] suggested the involvement of salivary cytokines, chemokines, and growth factors with salivary gland dysfunction as these molecules are produced as a result of persistent inflammation in salivary glands affecting the function of acinar cells.…”