## 4 Discussion
Given the above, it seems reasonable to suggest that the understanding of IL-1\(\beta\) dynamic in crevicular fluid in the context of periodontitis -CKD relationship, is far from clear. Our research targeted measurement of the oral gingival fluid levels of MMP-8 (neutrophilic collagenase) produced by activated neutrophils [66]. Biological functions of this collagenase are still not fully unfolded, although it is involved in numerous tissue remodeling processes associated to inflammatory or healing events [67; 68; 69]. MMPs and especially MMP-8 are involved in kidney pathology, through their tissue destruction ability [29], resulting in chronic remodeling and kidney fibrosis, found in diabetic nephropathy, polycystic kidney disorder and glomerulorphitis [70]. In addition, MMPs are part of the kidney inflammatory regulation network [70]. MMP-8 and MMP-9 have been identified in diabetic nephropathy patients' urine, supporting this molecule's involvement in its pathogeny [71]. Several studies have linked MMPs to periodontitis [29], MMP-8 being the main collagenase (80%) identified and analyzed in the gingival tissue and GCF [72]. Periodontal bacteria stimulate immune cells, which, in turn, produce and release MMP-8 into the blood stream, so that serum MMP-8 records higher levels in generalized and invasive periodontitis patients [73]. Current data support the relationship between periodontal bacteria (_F. nucleatum, P.s gingivalis, T. deticola, Aggregatibacter actinomycetemcomitans_) and MMP production, either directly or through neutrophil activation [74]. In periodontitis, high crevicular levels of MMP-8 are reported [75; 76; 77], the recognized variations emphasizing further that MMP-8 may be an indicator of lesion induction and progression [78]. However, keeping in mind the variability of the methods used for GCF collection, it should not be surprising the result that support the absence of statistic significant differences between crevicular MMP-8 levels in periodontitis versus control groups [79; 80]. MMP-8 crevicular values reported in the literature vary: 95.20 ng/mL in healthy subjects [77], 240.24 ng/mL [79; 80] and 428.60 ng/mL [77], respectively, in patients with periodontitis. A seminal article for the study of the CKD and periodontitis relationship, that analyses the salivary expression of MMP-8, suggests that periodontal inflammation may trigger systemic conditions, including CKD [29] Despite the numerous proof that suggest MMPs connection with periodontitis and CKD etiopathogeny, this potential route is far to be confirmed. More so, the current literature does not include data on the crevicular expression of MMP-8 in CKD. Our results registered distinct elevation of mean GCF MMP-8 level--18.80 \(\pm\) 27.75 ng/mL in patients with declined renal filtration rate, in contrast with control group values of 5.35 \(\pm\) 0.37 ng/mL. As well as for the other investigated markers, the mean MMP-8 levels were higher in hemodialysis patients with periodontitis, compared to patients with periodontitis without kidney involvement, with statistically significant differences between the two groups (\(p\) < 0.001). Moreover, through the significant differences in MMP-8 values, our data show a correlation of this biomarker to periodontitis aggressiveness indicated by its staging. Accordingly, our data suggest that MMP-8 play a pivotal role in the immune-inflammatory blueprint of periodontitis-associated end-stage renal disorder, compared with periodontitis without systemic damage. In the same register with the previous comments, we consider that this information, regarding the MMP-8 expression at crevicular level in the context of the periodontitis--CKD association emphasize higher GCF collagenolytic MMP-8 activity, GCF constituents being thus candidate biomarkers that might reflect the interplay between local periodontal and systemic inflammation, respectively. Hemodialysis patients are characterized by an immune deficiency that contributes greatly to the increased incidence and rapid evolution of periodontitis [81].