## 4 Discussion
On the other hand, serum osmolality is an objective indicator for the evaluation of hydration [12,13]. In HD patients, the change in serum osmolality is related to cerebral perfusion, oxygenation, and an increased risk of death. Plasma osmolality is higher in ESKD patients in the range of 291-339 mOsm/kg than that in the general population (275-290 mOsm/kg) [48, 49, 50]. In our study, the mean serum osmolality is 310.27 \(\pm\) 9.97 mOsm/kgH2O, which was compatible with the range in ESKD patients. We stratified the patients into two groups by the definition of cardiomegaly, and the serum osmolality was significantly lower in patients with cardiomegaly. Previous studies had found hypoosmality to be a risk for mortality in patients with heart failure not undergoing dialysis [51,52]. More recently, a prospective cohort study of 1240 HD patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS phase 5, 2012-2015) had displayed that a low predialysis osmolality was associated with intra-dialytic instability and was also an independent risk factor for all-cause mortality. Our research has also validated the significant linear correlation between salivary conductivity and blood osmolality in HD patients (Table 3). As the serum osmolality detection is inconvenient and cannot immediately reflect real-time changes of intravascular volume, it would be difficult for us to correct cerebral hypoperfusion or hypoxia during dialysis in time [48]. Moreover, frequent venipuncture is an invasive procedure that often causes the risks of vascular access-related complications, procedural pain, venous stenosis, infections, and increases morbidity and hospitalization, especially in ESKD patients [12, 21, 22, 23, 53, 54]. Moreover, ESKD is a disease of kidney damage, with little urine amount, which is difficult for further examination [55]. Thus, the salivary examination may provide an opportunity for rapid and real-time monitoring of fluid or cardiac states in ESKD patients during dialysis therapies. There are several limitations to be mentioned in this study. First, this is a cross-sectional design, thus we could not confirm a true cause and effect relationship between salivary conductivity and CTR. Second, we measured salivary data once in prevalent HD patients, thus there was no tangible baseline data and we could not evaluate the effect of serial changes of salivary conductivity on heart size. Third, we only used the CTR by chest radiography to define cardiomegaly. The misclassification of study patients into the wrong category may occur. Further studies with echocardiographic parameters and biomarkers for heart failure or hypervolemia are warranted to solve this weakness. Fourth, the relatively low AUROC value indicated a poor diagnostic performance of using the single parameter of salivary conductivity on cardiomegaly. Notably, when combined with serum sodium and a history of diabetes mellitus, the diagnostic accuracy is significantly increased. In addition, there was a lack of stomatal examination in our patients. Local pathological conditions of dental or periodontal tissues may affect the biocomponents in saliva, thereby interfering with the stability of the conductivity measurement. Finally, we did not consider the effects of anti-hypertensive or anti-arrhythmic medications on cardiac size.