*3.6. Nitrosative Stress Products*

NO concentration was significantly lower in NWS, SWS, and plasma in CKD children with hyposalivation compared to other groups. The concentration of S-nitrosothiols was significantly higher in NWS and SWS of children with chronic kidney disease and hyposalivation compared to CKD patients with normal salivary secretion and healthy controls. However, it did not differ significantly in plasma. The content of peroxynitrite and nitrotyrosine was significantly higher in NWS, SWS and plasma of CKD children with hyposalivation in comparison with the other groups (Figure 4).

**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.

#### *3.7. Correlations*

In CKD children the concentration of redox biomarkers in NWS and SWS correlated negatively with eGFR and positively with serum creatinine and urea (except for total thiols and tryptophan). However, no correlation with renal function parameters was generally observed in healthy subjects (Table 3).

In children with CKD, the concentration of protein and lipid oxidation products correlates negatively with salivary flow rate, salivary amylase activity and total protein content. Only salivary tryptophan and thiol groups correlated positively with salivary glands activity (Table 4). In NWS, glycooxidation products (except tryptophan), 4-HNE, 8-isop and peroxynitrite correlated positively with salivary pH. However, there was no relationship between the assessed biomarkers in saliva and plasma (except for kynurenine) (Table 5).

In the control group, dityrosine, kynurenine, tryptophan, AGE, and 4-HNE in non-stimulated saliva correlates positively with their plasma levels (Table 5). However, no relationships between cellular oxidation products and salivary gland function were demonstrated (except for AGE in SWS) (Table 4).


**Table 3.** Correlations between analyzed redox biomarkers and renal function of children with chronic kidney disease (CKD) and healthy controls.

4-HNE – 4-hydroxynoneal protein adducts; 8-isop—8-isoprostanes; AGE—Advanced glycation end products; C—Healthy controls; Cr—Creatinine; CKD—patients with chronic kidney disease; eGFR—estimated glomerular filtration rate; NWS—Non-stimulated whole saliva; SWS—Stimulated whole saliva. Statistically significant correlations (*p* < 0.05) are highlighted as bold and italics.



4-HNE—4-hydroxynonealNWS—Non-stimulated whole saliva; SA—Salivary amylase; SWS—Stimulated whole saliva. Statistically significant correlations (*<sup>p</sup>* < 0.05) are highlighted as bold and italics.


**Table 5.** Correlations between salivary and plasma redox biomarkers in children with chronic kidney disease (CKD) and healthy controls.

4-HNE—4-hydroxynoneal protein adducts; 8-isop—8-isoprostanes; AGE—Advanced glycation end products; C—Healthy controls; CKD—Patients with chronic kidney disease; NWS—Non-stimulated whole saliva; SA—Salivary amylase; SWS—Stimulated whole saliva. Statistically significant correlations (*p* < 0.05) are highlighted as bold and italics.
