The association between periodontal conditions, inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis patients

Abstract Objectives To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. Material and Methods We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. Results One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. Conclusions High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.

The causes of inflammation in hemodialyzed patients are multifactorial. They include poor oral hygiene and worse dental and periodontal state 4,8 .
Oral manifestations include halitosis, decrease in salivary secretion -so thirst, xerostomia, increase in salivary pH and salivary urea concentration, uremic stomatitis, calcification of the pulp chamber 5 .
Xerostomia, the subjective feeling of a dry mouth, is relatively common in hemodialyzed patients and is associated with difficulties in chewing, swallowing, tasting and an increased risk of oral disease (infections, dental caries, periodontal disease).
This condition can be caused by the use of certain medications, restriction of fluid intake and old age 6 .
There are inconclusive outcomes regarding the prevalence of caries in hemodialysis patients.
In contrast, most studies describe a high incidence of periodontal disease in these patients, where poor oral hygiene with increased deposits of plaque and calculus, identifying the presence of gingival inflammation, deep periodontal pockets, clinical attachment level loss and bone loss 5,7 . Furthermore, the dental health status got worse with the duration of hemodialysis treatment 8 .
Borawski, et al. 9 , (2007) found a more severe level of periodontitis in hemodialysis patients than in predialysis chronic kidney disease and peritoneal dialysis patients and finally, more advanced periodontitis in these investigated groups when compared to the control group.
Chronic periodontitis is an inflammatory, multifactorial disease of the periodontal tissues, in which the presence of periopathogens in microbial biofilm is the main initial factor. Moreover, both the quantity and virulence of the periopathogens and host-related general and local risk factors are determinants of the start and progression of periodontal inflammation and loss of periodontal tissue. The increased level of Gram-negative microorganisms responsible for the development and progression of periodontal inflammation increases the immunological response to bacterial antigens 7,10 . This may be the link between periodontal disease and CKD due to a concomitant infection and inflammation. A study found that the periodontitis in CKD patients was severer, with increased frequency in the presence of periopathogens and showed a strong association with kidney disease 11 . Periodontal disease is prevalent in kidney failure patients and it can also be, though not always, observed in this group because of the lack of interdisciplinary care for these patients 12 .
The objective of this study was to analyze the association between periodontal conditions and inflammation, nutritional status and calciumphosphate metabolism disorders in hemodialysis patients.

Material and methods
The patients were recruited in two dialysis centers A single dentist performed a complete dental/ periodontal examination, including the parameters of oral hygiene and gingival bleeding.
Dental assessment was performed before HD to exclude the effect of heparin, routinely used during the HD procedure.
Before starting the examination, the dentist was  Table 1 shows the demographic, clinical, and laboratory parameters of the study patients at the start of the study. The data are shown separately for dentate and edentulous groups.

Results
The dentate group was composed by 103 patients We found particularly interesting that only one person had a healthy periodontium. The oral hygiene and gingival bleeding parameters were not proper, given that the API index was 71.55±18.22% (minimum 18%/maximum 100%) and the BoP index was also high, with a mean value of 51.47±13.26% (minimum 10%/maximum 87%). The mean PD was 3.41±0.80 mm (minimum 1.75 mm/maximum 6.5 mm); data shown in Table 1  The comparison of the tested parameters (shown in Table 3) between the subgroups of patients (with gingivitis and periodontitis) showed that the group with a healthier periodontal state (H and G) was significantly younger, started hemodialysis earlier and had twice as many teeth as the group with diagnosed periodontitis (P 2 and P 3 ).
Both subgroups of patients had inflammatory markers (CRP) and calcium-phosphate metabolism (sAP, sP and PTH) parameters above the normal range values and sCa below the normal range -but there were no significant differences between the subgroups.
Spearman's rank correlation coefficient was used for the analyses of association (data in Table 4) and showed that the age at HD onset had a strong positive impact on indices of periodontal status (API index, BoP index and PD) and was negatively correlated with the number of teeth.
There was also a significant positive correlation between age and level of C-reactive protein, and negative correlations between age and levels of serum albumin and phosphorus.
PD was negatively correlated with serum albumin concentration.
The number of teeth showed strong negative correlation with serum CRP.

Discussion
This study confirmed the high incidence of poor oral condition in hemodialysis patients 16 . In our study we found that an older age of patients when starting dialysis was correlated with worse oral hygiene, more severe gingival inflammation and deeper pockets. Additionally, older age was associated with the presence of fewer teeth. Interestingly, Palmer et al. 23 (2015), in a cohort study with 4205 participants, found that poorer dental health was associated with early death.
For the healthy population, the normal range of CRP level is described as up to 5 mg/L and the range of 5 to 10 mg/L is considered as "high normal". For both groups. dentate and edentulous, CRP levels were only slightly above a "high normal" level. The data showing almost identical mean CRP levels in the subgroups of patients with gingivitis and periodontitis are particularly noteworthy. In this study, a higher level of serum C-reactive protein was associated with older patients, on the other hand, patients with a lower number of teeth showed a higher C-reactive protein level. These results do not confirm that only oral infection contributes to elevated C-reactive protein levels. The inflammation sources in hemodialysis patients can be multifactorial, and periodontal inflammation seems to be a source of the inflammatory reaction 24 . A similar conclusion is well-known and described in the literature 25  The serum calcium level did not differ between the dentate and edentulous groups or between groups with gingivitis and periodontitis. Also, no correlation between calcium level and periodontal status was observed. Kong, et al. 27 (2012), found that hemodialysis patients presented higher serum and salivary phosphorus levels, respectively, in comparison to peritoneal dialysis patients and the healthy group.
There was also no significant correlation between phosphorus level and periodontal state. Finally, only a higher serum level of this microelement in relation to the younger age of patients was observed. In our study, the main causes of chronic kidney disease were chronic glomerulonephritis (23.5% of patients), diabetic nephropathy (14%), interstitial nephropathy (13%), hypertension (12.5%) and others (37%). In other studies, the authors described the same common causes of the end-stage renal disease.
However, from the epidemiological point of view, the distribution of CKD causes in our research is not representative. This occurs due to the selection patients for the study -firstly the patient's consent, and in addition the elimination of patients with active inflammation, cancer history, or immunosuppression.
The limitation of our study was the relatively small sample size and the selected cohort of patients.

Conclusions
In conclusion, our data showed high prevalence and severity of periodontal diseases in hemodialysis patients.
We suggest that there is a high probability that periodontal disease may be present at the early stages of CKD before the hemodialysis treatment started.
Our results reinforce the opinion that oral health promotion, regular dentist assessment, and preventive programs in the period before dialysis can be helpful in changing individual behaviors and reducing the occurrence of irreversible forms of periodontal disease in these particular high cardiovascular risk patients.
Further studies are necessary to assess the potential contribution of periodontal disease to the inflammatory status in hemodialysis patients.

Conflicts of interest
The authors declare that they have no conflict of interest.