## 4 Discussion
Some studies show similar data for patients with periodontitis and patients without periodontal involvement [47; 48], or minimal differences between the levels found in periodontal healthy sites and those with periodontitis [49; 50]. Other studies point out considerable increase of crevicular TNF-\(\alpha\) in periodontitis [51; 52; 53], supporting the fact that TNF-\(\alpha\) concentration variations can be used to predict the progression of periodontal condition. To the best of our knowledge, a single study has evaluated crevicular TNF-\(\alpha\) (along with IL-8) in patients undergoing hemodialysis [54], resulting in a positive correlation between clinical indicators of periodontitis and CKD, and TNF-\(\alpha\) and IL-8 levels, as well as statistically significant differences between the two biomarkers, in the CKD group compared to control [54]. In our study, TNF-\(\alpha\) mean values in CGF in the study group ranged between 22.85 \(\pm\) 5.87 pg/mL, and in the control group between 2.10 \(\pm\) 1.34 pg/mL. Both values are comparable to the limited existing data (31.40 pg/mL, and 3.06 pg/mL, respectively) for crevicular analysis [54], confirming a ten-fold increase of TNF-\(\alpha\) levels in periodontally affected patients on dialysis. Moreover, our data showed that TNF-\(\alpha\) differs significantly between groups, in each of the periodontitis stages. Thus, regardless of the poorly understood relationships between periodontitis, renal disease and chronic inflammation, our research provides additional evidence for TNF-\(\alpha\) involvement in periodontitis and end stage kidney disorder interrelationship, hence supporting a potentiation of the inflammatory burden that aggravates kidney disease. In subjects with end stage renal disease, plasma IL-1 and IL-1 Ra levels may indicate a worse cardiovascular prognostic [55; 56; 57]. For the crevicular IL-1\(\alpha\) levels in periodontitis, a mean value of 198.33 pg/mL \(\pm\) 44.17 is reported [58]. In assessing the periodontal status, numerous studies claim the potential of IL-1\(\beta\) burden as a marker of differentiation between healthy and injured sites [50; 59; 60; 61; 62]. However, this differentiation is more evident in the case of advanced forms of periodontitis [60; 63], compared to early stages or to gingivitis [64]. The literature review points only one study that analyses crevicular IL-1\(\beta\) in end stage kidney failure. This recent investigation [65] evaluates together with IL-1\(\beta\) also IL-6, IL-8 and C reactive protein (CRP) in serum and GCF, in patients with end stage CKD, compared to a healthy control group. The results indicate the absence of statistic significant differences between the levels of crevicular fluid IL-1\(\beta\) of both groups [65]. Mean values of crevicular IL-1\(\beta\) were 0.26 ng/mL in the CKD group and 0.34 ng/mL in the healthy control group [65]. However, the study was limited by the small study population. In our study, the mean level of IL-1\(\beta\) in the study group was 33 \(\pm\) 39.68 pg/mL, and in the control group--10.4 \(\pm\) 15.95 pg/mL, with statistically significant differences between the two groups. Hence, our results acknowledge higher GCF mean levels of IL-1\(\beta\) in hemodialysis patients with periodontitis, compared to patients with periodontitis without kidney impairment. This pattern represents evidence suggesting the role of cytokines in the immune inflammatory mechanism that characterizes the two pathological entities, in contrast to the data from [PERSON] et al., who report a higher mean IL-1\(\beta\) level in the control group [65]. In our opinion, these contradictory results may be explained by the small sized group used by [PERSON] et al., in his study (15 subjects per group). On the other hand, when analyzing our data related to the periodontitis staging, there were no significant differences in IL-1\(\beta\) levels between the study and control groups, in any stage.