The Effects Of Periodontal Disease On Systemic Inflammation,Nutritional Status And Lipid Metabolic Level In End-stage Renal Disease Patients

The health of tooth and periodontal tissues is the one of the ten health criteiras according to the world health organization (WHO). The health of tooth and periodontal tissues is considered to be one of the three non-infectious diseases after cardiovascular disease (CVD) and cancer. The oral disease is the commen in general population and can affect the general health, especially the periodontal disease, which is the first reason of tooth loss in adults in our country. At present, more and more attention was put on the oral health status of end-stage renal disease (ESRD) patients especially undergoing hemodialysis (HD) therapy. The oral health status of ESRD patients have been reported reported in some countries, but rarely reported in China.Some research indicated that periodontitis can increase the systemic inflammatory burden. Chronic periodontitis is a chronic infection caused by bacteria in periodontal tissue. The destruction of periodontal tissue and ulcer of periodontal pocket wall were caused by the periodontal pathogenic bacteria and their toxic products function. One study has shown that, the ulcer area of periodontal pocket wall with severe periodontitis can come up to72cm2. And the vascular permeability of periodontal tissue increased with inflammation. So brushing teeth, treating oral diseases and chewing hard objects can make periodontal pathogens and their toxins into the blood, which can cause a transient bacteremia and aggravate systemic inflammatory response. In addition, periodontal pathogens and toxic products can also stimulate localized expression of interleukin-6(IL-6), tumor necrosis factor-a (TNF-a) and prostaglandin E2,(PGE2) in periodontal tissues. These inflammatory mediators were released into blood, and then further systemic reactions were exacerbated. The serum C-reactive protein (CRP) concentration increased. Some cross-sectional stidies and few intervational studies have been reported about the effects of periodontal disease on the systemic metabolic status in ESRD patients. The effects of periodontal disease on ESRD and the mechanism deserved further more research.The paper includes the following three parts:Part One-The correlations of clinical oral health status with demographiccharacteristics, systemic inflammation, nutritional status and lipid metabolic level in ESRD patientsFirst Section-The demographic characteristics and clinical oral health status in the study populationObjectives:To investigate the correlations between demographic characteristics such as age, gender, education level, income, marriage status, body mass index (BMI), smoking, alcohol drinking, physical exercise and clinical oral health status including dental caries and periodontal status in the ESRD patients undergoing HD therapy.Methods:From September2009to March2011,130patients undergoing stable hemodialysis treatment were recruited. We enrolled all ESRD patients from hemodialysis units of Nanfang Hospital, Zhujiang Hospital and General Hospital of Guangzhou Military Command of People’s Liberation Army. The patients had been undergoing on average4h of hemodialysis3times/wk. Before oral health parameters were collected, all subjects were asked to fulfil a questionnaire with items including general information, medical history, family history, medications used, dental history, duration of dialysis, primary renal disease and oral health behaviors. All participants were asked not to brush their teeth or eat breakfast before the examination. Clinical oral examination of ESRD patients included the dental caries and periodontal status. The dental caries status was assessed using the prevalence of caries and decayed, missing and filled teeth (DMFT) index. The periodontal indices included plaque index (PLI), gingival index (GI) and periodontal disease index (PDI). All statistical analyses were performed using SPSS17.0Chinese Edition (SPSS Inc., Chicago, IL, USA).Results:A significant correlation was found between DMFT index and age in ESRD patients. In the aged group, the value of DMFT index was higher (P<0.001). No significant correlation was found between caries indices and gender (P>0.05). The values of missing teeth and DMFT index in the lower income group were significantly lower than those in the higher income group (P=0.003). The significant differences were found between caries teeth, missing teeth, DMFT index and marriage status (P<0.05). No significant correlation was found between BMI, smoking, alcohol drinking, physical exercise and dental caries indices (P>0.05). The DMFT value was significantly correlated with oral health behaviors (P<0.001).For the periodontal status, we found that the PDI value was significantly higher in the aged group (P<0.001). In the lower income group, the PDI value was significantly higher than in the higher income group (P<0.001). The PDI value had significant difference between groups according to the marital status (P=0.003). No significant correlations were found between gender, education level, BMI and clinical periodontal indices (P>0.05). In the current-smoking group, the PDI value was significantly higher than that of formed-smoking or never-smoking group (P=0.020). The PDI value was significantly correlated with oral health behaviors (P<0.05). Conclusions:Some demographic characteristics were significantly correlated oral health indices. These factors may have an effect on the dental caries and periodontal status in ESRD patients.Second Section-The effect of the duration of dialysis on oral health status in the study populationObjectives:To investigate the effect of duration of dialysis on oral health status in ESRD patients.Methods:The population of this study was the same as the first section. According to the duration of dialysis, they were divided into three subgroups (≤18months,>18-≤42months,>42months). The dental caries and periodontal status were determined and then compared between the three subgroups according to the duration. The correlations between oral health indices and duration were analyzed. All statistical analyses were performed using SPSS17.0Chinese Edition (SPSS Inc., Chicago, IL, USA). The Spearman rank correlation coefficients were evaluated between oral health indices and duration of dialysis.Result:The dental caries indices had no significant difference between the three groups (P>0.05). The PLI, GI and PDI values increased with the duration (P<0.05). No significant correlation was found between DMFT index and duration (P=0.821). And significant positive correlations were observed between periodontal indices and duration (P=0.022,0.006and0.004, respectively).Conclusions:The periodontal status in ESRD patients becomes worse with time on dialysis. Duration of dialysis is a confounding factor when investigating the periodontal status in ESRD patients undergoing HD therapy.Third Section-The correlations of periodontal status with systemic inflammation, nutritional and lipid metabolic levels in ESRD patientsObjectives:The cross-sectional study was performed to investigate the effects of periodontal disease on systemic inflammation, nutritional status and lipid metabolic levels in ESRD patients.Methods:The population of this study was the same as the first section. The PLI, GI and PDI were used to assess the periodontal status. According to PDI values, they were divided into four subgroups. The no periodontitis group included30patients. The mild periodontitis group included35patients. The moderate periodontitis group included42patients. The severe periodontitis group included23patients. The inflammatory markers included TNF-a, IL-6, CRP and ferritin. The nutritional markers included albumin (Alb), blood urea nitrogen (BUN), creatinine (Cr), absolute lymphocyte counts (ALC), transferrin (Tf) and normalized protein catabolism rate (nPCR). The lipid metabolic markers included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). To determine the differences in levels of systemic inflammation, nutritional status and lipid metabolic level, multiple linear regression was performed after adjusting for age, yearly income, marriage status and dialysis duration. The Pearson Partial Correlations were used to calculate the correlations among systemic parameters and periodontal indices after adjusting for cofounding factors. To identify independent factors associated with PDI, we used multiple linear regression models with stepwise procedures for biochemical and demographic variables. All statistical analyses were performed using SPSS17.0Chinese Edition (SPSS Inc., Chicago, IL, USA).Result:The significantly positive correlations between the severity of periodontitis and systemic inflammatory markers were found after controlling for confounding factors (P<0.01).We also found the significant correlation between nutritional parameters and periodontal indices (P<0.05). IL-6was independently associated with the severity of periodontitis in ESRD patients with multiple regression analysis.Conclusions:These results suggest that periodontal status is poor and correlates with systemic inflammation and nutritional status in ESRD patients. In this special population, periodontal disease may be a risk factor for systemic inflammation and malnutrition. Its diagnosis and treatment deserve a more thorough approach.Part Two-The comparison of oral health and salivary parameters between the ESRD patients and systemically healthy controlsFirst Section-The comparison of dental caries and periodontal status between the ESRD patients and systemically healthy controlsObjectives:To compare the dental caries and periodontal status in ESRD patients with systemically healthy controls.Methods:The case group of this study was the same as the first section of part one. Generally healthy individuals were selected as control subjects from the people coming to Health Control Centre of Nanfang Hospital for their annual physical check-up from September2009to March2011. The controls were matched for age (±3years) and gender. The dental caries and periodontal status were evaluated by the same methods as the first section of part one. All statistical analyses were performed using SPSS17.0Chinese Edition (SPSS Inc., Chicago, IL, USA).Results:The dental caries indices had no significant differences between the two groups. The values of decayed teeth and filled teeth was no significantly lower in the case group than in the control group (P=0.095and0.054, respectively). The value of missing teeth was no significantly higher in the case group than in the control group (P=0.423). The value of DMFT index was no significantly lower in the case group than in the control group (P=0.581). The prevalence of dental caries were67.69%and76.92%, respectively in the case and control group(P=0.096). The periodontal indices were all significantly higher in the case group than in the control group (P<0.001). Also a significant difference was found about the severity of periodontitis between the two groups (P<0.001).Conclusion:Compared with systemically healthy controls, the periodontal status was worse in ESRD patients.Second Section-The comparison of salivary parameters between ESRD patients and systemically healthy controlsObjective:To investigate the salivary parameters in ESRD patients, and the correlations with dental caries status.Methods:Based on the study the first section of part two, a total of76ESRD patients meeting the inclusion criteria were included. And also the controls were matched with age (±3years) and gender. The dental caries and salivary parameters were compared between the two groups. Then the correlations of DMFT with salivary characteristics were evaluated in the two groups. The salivary characteristics included salivary flow rate (SFR), salivary buffer capacity (SBC) and salivarypH (SpH). All statistical analyses were performed using SPSS17.0.Results:No significant difference was found about the dental caries status between the two groups. The prevalence of caries was64.47%and71.05%in the case and control group, respectively (P>0.05). The value of DMFT index was not significantly lower in the case group than in the controls (P=0.264). The value of SFR in the case group is significantly lower than in the control group (P<0.001). The values of SpH and SBC were both significantly higher than in the control group (P<0.001).In the case group, no significantly negative correlation was found between the value of DMFT and SFR (r=-0.112, P=0.335). Also no significantly negative correlation was found between the value of DMFT and SpH (r=-0.106, P=0.364). A significantly negative correlation was found between the value of DMFT index and SBC (r=-0.322, P=0.005). In the control group, significantly negative correlations were found between the value of DMFT index and SFR, SpH, SBC (P<0.01). Conclusions:The increased SBC may be an important factor for the relatively decreased prevalence of caries in ESRD patients.Part Three-The effect of non-surgical periodontal therapy on periodontal status and systemic metabolic status in ESRD patientsObjective:The randomized, controlled and blinded clinical trial was to investigate the effect of non-surgical periodontal therapy on periodontal status, systemic inflammation, nutritional status and lipid metabolic level in ESRD patients.Methods:ESRD patients were randomly divided into two groups (treatment group and control group) using simple random number table, treatment group and control group. During the study period, the controls didn’t receive the periodontal treatment. Blind method:The periodontist assessing the periodontal status didn’t know the treatment procedure. Questionnaire investigation was the same as the first section of part one. The periodontal indices included PLI, bleeding on probing (BOP), pocket probing depth (PPD), gingival recession (GR) and clinical attachment loss (CAL). The markers of systemic inflammation, nutritional status and lipid metabolic level were assessed as the first section of part one. The examination of periodontal status and biochemical parameters were performed4times (baseline,6weeks after non-surgical periodontal therapy,3months after non-surgical periodontal therapy,6months after non-surgical periodontal therapy). All statistical analyses were performed using SPSS17.0Chinese Edition (SPSS Inc., Chicago, IL, USA).Results:46cases in treatment group and47cases in control group completed the study. No significant difference was found at baseline about the characteristics of the two groups (P>0.05). The PLI、BOP(+)%、PPD、PPD≤3mm%、PPD4-5mm%、 PPD≥6mm%、GR and CAL showed significant changes in the treatment group during the study period (P<0.01). Significant differences were found between the two groups about PLI、BOP(+)%、PPD、PPD≤3mm%、PPD4-5mm%and PPD≥6mm%at the6months (P<0.05). The inflammatory markers CRP、IL-6and ferritin decreased significantly after non-surgical periodontal therapy in the treatment group (P<0.05). The nutritional parameters A1b、Cr、BUN and Tf increased significantly after non-surgical periodontal therapy in the treatment group (P<0:05). The lipid metabolic level showed no significant change during the study period in the two groups (P>0.05).Conclusion:Non-surgical periodontal therapy can control the periodontal infection, and the treatment effect achieved the best at6months. The systemic inflammation decreased significantly after non-surgical periodontal therapy in the treatment group. The nutritional status increased better after non-surgical periodontal therapy. The lipid metabolic level showed no significant change during the study period. Periodontitis potentially is a treatable factor of chronic inflammation in ESRD patients. Therefore, periodontitis in ESRD patients may be a covert source of systemic inflammation that can be managed through effective non-surgical periodontal therapy. Therefore, its diagnosis and management deserve better awareness.In conclusion, our research found that some demographic characteristics were correlated with oral health status in ESRD patients. Compared with systemically healthy controls, the periodontal status was worse in ESRD patients. The increased SBC may be an important factor for the relatively decreased extent of caries in ESRD patients. Periodontal status was poor and correlated with systemic inflammation and nutritional status in ESRD patients. Non-surgical periodontal therapy can effectively improve periodontal inflammation, systemic inflammation and malnutrition status in the ESRD patients with periodontitis. Periodontal disease may be a risk factor for systemic inflammation and malnutrition in ESRD patients undergoing HD therapy.