Salivary Gland Dysfunction, Protein Glycooxidation and Nitrosative Stress in Children with Chronic Kidney Disease

Abstract

This study is the first to evaluate protein glycooxidation products, lipid oxidative damage and nitrosative stress in non-stimulated (NWS) and stimulated whole saliva (SWS) of children with chronic kidney disease (CKD) divided into two subgroups: normal salivary secretion (n = 18) and hyposalivation (NWS flow < 0.2 mL min^-1; n = 12). Hyposalivation was observed in all patients with severe renal failure (4-5 stage CKD), while saliva secretion > 0.2 mL/min in children with mild-moderate CKD (1-3 stage) and controls. Salivary amylase activity and total protein content were significantly lower in CKD children with hyposalivation compared to CKD patients with normal saliva secretion and control group. The fluorescence of protein glycooxidation products (kynurenine, N-formylkynurenine, advanced glycation end products), the content of oxidative damage to lipids (4-hydroxynonneal, 8-isoprostanes) and nitrosative stress (peroxynitrite, nitrotyrosine) were significantly higher in NWS, SWS, and plasma of CKD children with hyposalivation compared to patients with normal salivary secretion and healthy controls. In CKD group, salivary oxidation products correlated negatively with salivary flow rate, -amylase activity and total protein content; however, salivary oxidation products do not reflect their plasma level. In conclusion, children with CKD suffer from salivary gland dysfunction. Oxidation of salivary proteins and lipids increases with CKD progression and deterioration of salivary gland function.

Keywords: chronic kidney disease; nitrosative stress; oxidative stress; salivary biomarkers; salivary gland dysfunction.

Figure 1

Salivary gland function and salivary pH of children with chronic kidney disease (CKD) and healthy controls. C—Healthy controls; CKD NS—CKD patients with normal salivary secretion; CKD HS—CKD patients with reduced salivary secretion; NWS—Non-stimulated whole saliva; SA—Salivary amylase; SWS—Stimulated whole saliva. Differences statistically significant at: * p < 0.05, ** p < 0.005, **** p < 0.0001.

Figure 2

Glycooxidation products in children with chronic kidney disease (CKD) and healthy controls. AGE—Advanced glycation end products; C—Healthy controls; CKD NS—CKD patients with normal salivary secretion; CKD HS—CKD patients with reduced salivary secretion; NWS—Non-stimulated whole saliva; SWS—Stimulated whole saliva. Differences statistically significant at: * p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.0001.

Figure 3

Oxidative damage to proteins and lipids in children with chronic kidney disease (CKD) and healthy controls. 4-HNE—4-hydroxynoneal protein adducts; 8-isop—8-isoprostanes; C—Healthy controls; CKD NS—CKD patients with normal salivary secretion; CKD HS—CKD patients with reduced salivary secretion; NWS—Non-stimulated whole saliva; SWS—Stimulated whole saliva. Differences statistically significant at: * p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.0001.

Figure 4

Nitrosative stress in children with chronic kidney disease (CKD) and healthy controls. CKD NS—CKD patients with normal salivary secretion; CKD HS—CKD patients with reduced salivary secretion; NO—nitric oxide; NWS—non-stimulated whole saliva; SWS—stimulated whole saliva. Differences statistically significant at: * p < 0.05, ** p < 0.005, **** p < 0.0001.