| Periodontitis, one of the two top dental diseases, is a chronic inflammatory disease of periodontal tissues with high prevalence worldwide. In China, the prevalence of periodontitis is even higher than that of dental caries. According to the third national epidemiological investigation of oral health,90%of the population is affected with various periodontal diseases. It occurs in people of different age groups, but has higher prevalence in adults and the seniors. As China is entereing the senile society, periodontitis has become a serious oral health problem and the primary cause for tooth loss in adults.The dental biofilm microorganisms are the initiating factors of chronic periodontitis, to which the host’s inappropriate immune reaction is the main cause for the periodontal tissue destruction, which has been elucidated by a large number of investigations. The hosts’ differences in immune capability, hereditary trait, social behavior and so on are directly related with the occurrence, progression and outcome of periodontitis. Researchers have identified some of risk factors which may increase the prevalence of periodontitis and affect other systemic diseases; but, are these factors related to the severity of periodontitis? The question is directly related to the progression and outcome of periodontitis. Most of earlier studies focused on identifying risk factors which would increase the prevalence of periodontitis, and paid less attention to those which would increase the severity of periodontitis. However, as dentists, we are most concerned with the questions that whether the existed periodontitis can be controlled, or would it aggravate further. Therefore, it is significant to investigate the risk factors affecting periodontitis, and the findings will help dentists in their treatment to consider not only the damage of the oral cavity but also the systemic factors of the patients’whole body.Chronic kidney disease (CKD) is considered a global public health problem in the21st century, and ranked the third killer only after cancer and heart attack. In the field of medicine, great importance has been attached to its epidemiological studies and the study object has shifted from chronic renal failure (CRF) or end-stage renal disease (ESRD) to early CKD and related risk factors, which reflects the researchers’ changing and maturing understanding of CKD. Up to date, epidemiological studies of CKD usually take the general population as the subjects, there are also a small number of studies focusing on high-risk groups of CKD, such as those in the United States which examine the first-degree relatives of patients with hypertension and diabetes, or with high blood pressure, diabetes and kidney disease. The findings suggest that screening for CKD in the general population, the cost-effectiveness is relatively poor, while screening in high-risk groups (hypertension, elderly) has better cost-effectiveness.In the previous studies on the relationship between periodontal disease and CKD, the subjects were all patients with CKD or end-stage renal disease (ESRD), and these studies were either cross-sectional studies of a small size sample or independent studies on Western white and black population, while authoritative epidemiological study on the prevalence of CKD in Chinese chronic periodontitis patients is basically blank. This research is to establish the database about chronic periodontitis patients in South China and to analyze the relationship between various risk factors and the severity of periodontitis. It is the first time to collect and test urine samples of patients in chronic periodontal epidemiological investigation, and also the first time to report prevalence of albuminuria, hematuria, glomerular filtration rate (eGFR) and CKD in periodontitis patients. Based on all this, a further step will be taken to explore and analyze the risk factors affecting the severity of chronic periodontitis, CKD patients with chronic periodontitis, and those affecting both chronic periodontitis severity and CKD. The researches include:1. To establish questionnaire repository, clinical database and biological sample storage of Chinese patients with chronic periodontitis;2To screen and analyze risk factors related to periodontitis severity;3. To analyze incidence and risk factors of CKD in chronic periodontitis patients;4. To analyze common risk factors of chronic periodontitis severity and CKD.Mathods and Materials:Patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March2011and August2011. A total of1392patients with periodontal disease were screened and1268subjects met the criteria and completed the survey and examination.Subject inclusion criteria:patients diagnosed with chronic periodontitis, age>18years, with at least two functional teeth in a1/6quadrant according to the WHO-prescribed oral examination standards. Subject exclusion criteria:(1) edentulous(2) liver cirrhosis(3) malignant neoplasm; (4) subgingival scaling treatment in the previous1month(5) antibiotic treatment in the previous1month(6) acute infectious disease of the oral cavity or salivary glands in the previous6months.All participants completed a questionnaire documenting their socio-demographic status (e.g. age, sex, education and health insurance), personal and family health history (e.g. diabetes, hypertension, cardiovascular disease [CVD], and hyperlipidemia) and lifestyle behaviors (e.g. smoking and drinking) with the assistance of trained staff. A history of self-reported HBV infection and nephrotoxic medications (e.g. non-steroidal anti-inflammatory drugs and herbs containing aristolochic acid) were also been recorded. All participants underwent a thorough periodontal examination by dentists, who were trained following a standard examiner, including periodontal probing pocket depth (PPD), gingival recession, and clinical attachment level (CAL). All measurements were performed and documented in all teeth (third molars were excluded), on six sites per tooth, which were distal buccal (DB), distal lingual (DL), mesial buccal (ML), mesial buccal (MB), straight lingual (L), and straight buccal (B) sites, using the Florida Probe System (Florida Probe(?); Florida Probe Corp. Gainesville, FL).Laboratory tests include:(1) biochemical indicators:renal function, random blood glucose, uric acid, blood with homocysteine, lipids (triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol (2) early screening for kidney disease:ACR albumin-creatinine ratio, hematuria, eGFR (3) inflammatory factors:CRP, IL-1, IL-6, TNF-a.All subjects will be divided into three groups according to their PD value and CAL value in compliance with criteria recommended by Control and Prevention (CDC) center of the American Academy of Periodontology and into another three groups according to the proportion of bleeding loci in mouth total; all subjects will be compared according to the median of their periodontal epithelial coverage area (PESA) and periodontal inflamed surface area (PISA).CKD prevalence will be examined in this study with albuminuria, eGFR, hematuria as kidney damage index. The eGFR will be calculated with simplified MDRD formula adjusted to Chinese patients. According the standard of American National Kidney Foundation-Disease Outcome Quality Innitiative (NKF-DOQI), eGFR<60mL/min/1.73m2is diagnosed as reduced glomerular filtration rate Under a400-magnification optical microscope, red blood cells>3are defined as hematuria. Microalbuminuria and macroalbuminuria were defined as Albumin-creatinine ratio (ACR) between30～299mg/g respectively. The term "albuminuria" is used to describe the presence of either microalbuminuria or macroalbuminuria.Results:1.To establish questionnaire repository, clinical databases and biological sample library of Chinese patients with chronic periodontitis. Basic materials include the data and specimens of1268periodontitis patients, with423male cases (33.36%),845female cases (66.64%), of an average age of54(±10.85) years,73.34%with high school education, and174current smokers (13.72%). Average cholesterol, triglycerides, high-density lipoprotein, LDL levels were5.68±1.09mmol/L,1.95±1.50mmol/L,1.4±0.39mmol/L, and3.25±0.88mmol/L respectively. Among the hyperlipidemia,108patients (accounting for8.52%) had high-density lipoprotein<0.91mmol/L,825patients (65.06%) with cholesterol≥5.20mmol/L563patients (44.40%) with triglycerides≥1.70mmol/L,182patients (14.35%) with low-density lipoprotein≥4.14mmol/L. The median of serum inflammatory factors hsCRP, TNF-a, IL-6, IL-1β concentration were1.02mg/L,1.12ng/L, 7.60ng/L, and11.32ng/L respectively. Prevalence of albuminuria, hematuria, eGFR and CKD in the periodontitis patients of this study was6.70%,10.90%,2.70%, and18.20%respectively after adjusted for age and gender.2. To analyze risk factors related to chronic periodontitis severity;With the use of one-way ANOVA, the groups of mild, moderate and severe periodontitis, classified according to the criteria recommended by Control and Prevention (CDC) center of the American Academy of Periodontology, were found to be positively correlated with age (F=14.988, P<0.001); with the use of chi-square test, severity of periodontitis was found to be associated with gender (χ2=17.658, P<0.001), but not associated with education level. With the rise of the severity of periodontitis, moderate and heavy smokers increased in significant proportion (χ2=19.628, P <0.05); the mean concentration of four kinds of inflammatory factor in the serum of smoking group was higher than of that in nonsmoking group, and IL-1difference between the groups was statistically significant (t=-2.036, P<0.05). In patients with periodontal or high cholesterol family history, the overall constituent ratio of severe periodontitis was significantly higher than that in mild and moderate periodontitis, and was statistically different from patients without periodontitis family history. BMI, waist to hip ratio, systolic blood pressure, diastolic blood pressure, hs-CRP concentration in serum were all positively correlated with periodontitis severity and statistically significant. With Binary Logistic regression analysis, after adjusted for gender, education level, systolic blood pressure, diastolic blood pressure, and other confounding factors, age, gender, family history of high cholesterol were still found to be the risk factors of periodontitis severity.In patients with high school education or higher education, the BOP(Bleeding on probing) loci that account for30-60%and above60%of mouth total were lower in proportion than that in patients with lower education, and the difference was statistically significant (x2=10.545, P=0.005). It showed that education level was not related to gums inflammatory response. In subjects whose BOP loci account for more than60%of mouth total, the systolic blood pressure was significantly higher than that is ubjects whose BOP loci were less than60%(F=4.081, P=0.017), diastolic blood pressure and gingival inflammation severity were positively correlated and the differences were statistically significant (F=5.652, P=0.004).Subjects were divided into two groups by PESA median962.5and PISA median271.6. In subjects with PISA above the median (>271.6), the mean diastolic blood pressure was higher than those with PISA<271.6, and the difference was statistically significant (t=-2.505, P<0.012).In subjects with PESA>962.5, the diastolic blood pressure was higher than that of subjects with PESA<962.5, but the difference was not statistically significant.. After adjustment of some confounding factors in logistic regression analysis, age was found to be negatively correlated with PESA and diastolic blood pressure positively correlated with PISA. In smoking group of periodontitis patients, PESA above the median was significanty higher in proportion than that of the non-smoking group, and the difference was statistically significance (=5.995, P=0.014); a further research in smoking subjects found that, in subjects with light and moderate smoking index, the proportion of PESA above the median was higher than that in heavy smokers.The relationship between smoking and PISA is consistent with that between smoking and PESA, but the difference was not statistically significant. In group of hypertriglyceridemia (triglycerides≥1.7mmol/L), PESA above the median had higher proportion than that in the normal group, and the result was statistically significant (χ2=4.373, P <0.0,37). In group of PISA above and below the median, subjects with normal triglycerides and those with abnormal triglycerides were similar in proportion, without much difference. 3. To analyze incidence and risk factors of CKD in chronic periodontitis patients;In subjects of chronic periodontitis, the incidence of eGFR was2.7%(95%CI,1.7-3.7), and the awareness rate was28.1%. The prevalence of eGFR higher than that of the general population in China was1.7%(95%CI1.5-1.9), and at the same time than that of the general population of the South China was1.3%(95%CI1.0-1,6). The prevalence of reduced eGFR increased with age (P<0.001). Periodontal disease patients older than65years had a higher prevalence of reduced eGFR than those less than65years old (12.9%vs.1.2%,=68.983, P<0.001). The prevalence of reduced eGFR was greater in men than that in women (5.9%vs.0.8%,χ2=29.592,P<0.001). The prevalence of reduced eGFR in periodontal disease patients with diabetes, hypertension, a history of CVD, or hyperuricemia was significantly higher than those without these factors (all P values<0.001). The prevalence of reduced eGFR was greatest in periodontal disease patients with diabetes and hypertension (8.9%), whereas in those with neither diabetes nor hypertension, the prevalence was only1.8%(8.9%vs.1.8%,χ2=22.509,P<0.001;7.5%vs.1.4%,χ2=29.581, P<0.001). In addition, periodontal disease patients with a history of CKD had a higher prevalence of reduced eGFR than those without a history of CKD (7%vs.2%,χ2=11.759, P=0.001).The prevalence of eGFR in periodontitis patients with severe smoking index has reached6-8times of that in the periodontitis patients who were non-smokers or light smokers (13.1%vs.1.5%2.1%, Fisher’s Exact test, P<0.001). In chronic periodontitis patients with reduced eGFR, the mean values of systolic blood pressure, waist-to-hip ratio, and TNF-a, IL-1were higher than those without reduced eGFR (P <0.001), while the mean value of high-density lipoprotein was lower than those without reduced eGFR (P<0.005). Through logistic regression analysis, after adjusting for gender, age, education level, health care, graded smoking index, alcohol consumption, family history of diabetes, family history of hypertension, risk factors of reduced eGFR were age, male, heavy smoking.In subjects of this study, Microalbuminuria and macroalbuminuria were detected in6.0%(95%CI,4.7-7.2) and0.7%(95%CI0.2-0.9) respectively. The prevalence of albuminuria was6.7%(95%CI5.5-8.1) and the awareness rate was16.3%, greater than the prevalence of albuminuria in the general population in South China (6.0%).The prevalence of albuminuria increased with age (P<0.001). Periodontal disease patients older than65years had a higher prevalence of albuminuria than those less than65years (15.1%vs.6.8%,χ2=1.920, P<0.001). The prevalence of albuminuria was greater in women than that in men (9%vs.5.2%,χ2=5.687, P=0.017).Chronic periodontitis patients with albuminuria had higher mean value of BMI index, cholesterol, triglycerides, low-density lipoprotein, systolic blood pressure than those without albuminuria. Among them, the prevalence of albuminuria in periodontitis patients with BMI greater than or equal to24was two times of that of those with BMI lower than24(110%vs.6.00%, χ2=11.386, P=0.001). Periodontitis patients with diabetes, hypertension, history of cardiovascular disease, high blood cholesterol had higher prevalence of albuminuria than those without these diseases (P<0.05). Periodontitis patients with a CKD history had higher prevalence of albuminuria than those without (12.5%vs.7.2%χ2=4.545, P=0.033). Through logistic regression analysis, after adjusted for confounding factors such as age, gender, education, health care, diabetes, hypertension, cardiovascular disease, CKD history, graded smoking index, alcohol consumption, BMI, systolic blood pressure, the biochemical glucose, cholesterol, triglycerides, low-density lipoprotein cholesterol, TNF-a, risk factors of albuminuria were women, diabetes, systolic blood pressure, CKD history.Hematuria was present in10.9%and the awareness rate was15.9%in periodontal disease patients. The prevalence of hematuria was greater in women than in men (14.2%vs.8.7%,P=0.005). Periodontal disease patients with a higher education had a lower prevalence of hematuria than those without a higher education (10.3%vs.18%,χ2=11.636, P<0.001). The prevalence of hematuria in periodontal disease patients with light smoking index was significantly higher than that in nonsmokers (15.2%vs.13.1%,χ2=8.994, P<0.05). In chronic periodontitis patients with hematuria, the mean values of BMI, creatinine, glucose, uric acid were lower than that in those without hematuria, while the mean high-density lipoproteinn was higher (P<0.05).Patients with a history of CKD had a higher prevalence of hematuria than those without a history of CKD (19.5%vs.11.6%, P=0.01). After Adjustment for confounding factors such as age, gender, education, health insurance, diabetes, CKD history, graded smoking index, alcohol consumption, body mass index (BMI), creatinine, albumin, biochemical glucose, uric acid, high-density lipoprotein cholesterol, risk factors of hematuria were low level education and CKD history. As for the relationship between BMI (OR=0.928, P=0.026) and hematuria in the result, it remained unknown even after consulting renal specialists; as much still depended on follow-up experiments, we could not therefore define BMI as protective factor of hematuria in the present.After adjustment for age and gender, the prevalence of CKD in the subjects was18.2%(95%CI16.2-20.3), of which the first phase was11.6%(95%CI,9.9-13.3), the second phase3.9%(95%CI2.9-5.0), the third2.6%(95%CI1.6-3.6), and only one patient in the fourth phase, no patient in the fifth phase. The awareness rate was16.2%. The prevalence of CKD in periodontitis patients of all age groups increased with the rise of age. The prevalence of CKD in group above 65years of age was2times that of group below65years of age (37.4%vs.18.3%,=27.706, P<0.001), while the prevalence of CKD was inversely proportional to the level of education (18.5%vs.25.7%,8.006, P=0.005). The prevalence of CKD was higher in patients with diabetes, hypertension and CKD history (P<0.05). In periodontitis patients with CKD, the averages of age, serum creatinine, cholesterol, and LDL were higher than that in periodontitis patients without CKD (P<0.05).Through logistic regression analysis after adjusted for age, sex, education, health care, diabetes, hypertension, cardiovascular disease, CKD history, hepatitis carriers classification, graded smoking index, alcohol consumption, family history of periodontal disease, systolic blood pressure, waist-to-hip ratio, creatinine, albumin, biochemical glucose, cholesterol, triglycerides, low-density lipoprotein cholesterol, it was found that male, creatinine, CKD history were the CKD risk factors, and the high level of education was its protective factor (OR=0.665(95%CI0.487-0.909), P=0.01).In periodontitis patients with serum hsCRP(high-sensitive capsule-reactive protein)≥1.02mg/L,the prevalence of proteinuria, eGFR, and CKD was1.77times,2.16times and1.29times respectively that in periodontitis patients with serum hsCRP<1.02mg/L (P=0.004, P=0.035, P=0.022);In periodontitis patients with serum IL-1≥11.32ng/L, the prevalence of reduced eGFR was2.39times that in periodontitis patients with serum IL-1<11.312ng/L (χ2=5.415, P=0.02); in periodontitis patients with serum IL-6levels≥7.60ng/L, the prevalence of reduced eGFR was3.31times that in periodontitis patients with serum IL-6<7.60ng/L(χ2=9.103, P=0.003); in periodontitis patients with serum TNF-α>1.12ng/L, the prevalence of proteinuria was2.33times that in periodontitis patients with serum TNF-a<1.12ng/L(χ2= 5.129,P=0.024). These showed that the different concentrations of inflammatory factors in the serum of periodontitis patients had direct impact on the prevalence of CKD and were important mediating pathway.Conclusions:The main conclusions of the study are as follows:1. Age and sex are not just risk factors of chronic periodontitis but also risk factors of the severity of chronic periodontitis.2.In with heavy smoking index, the prevalence of severe periodontitis was higher than moderate and mild periodontitis (P<0.05). In the smoking group of chronic periodontitis patients, serum concentrations of IL-1β was higher than that in the non-smoking group, possibly mediated bad consequences of smoking to periodontal tissues and even other organs of the whole body.3.In patients with family history of periodontal disease or high cholesterol, the prevalence of severe periodontitis was higher than mild and moderate periodontitis (P<0.05)4.BMI, waist-hip ratio, systolic blood pressure, diastolic blood pressure, hs-CRP concentration in serum were positively correlated with periodontitis severity, and diastolic blood pressure was positively correlated to bleeding of gingival inflammation (P<0.05).5. After adjustment for confounding factors, age, gender, family history of high cholesterol were still risk factors for chronic periodontitis severity.6. It was found for the first time that in chronic periodontitis patients the prevalence of CKD was18%(95%CI16.20-20.30), the prevalence of reduced eGFR was2.70%(95%CI,1.70-3.70), microalbuminuria was detected in6.0%(95%CI4.7-7.2), macroabuminuria was detected in0.70(95%CI0.20-0.90), the prevalence of albuminuria was6.7%(95%CI5.5-8.1), the prevalence of hematuria was10.90%(95%CI9.20-12.50); all these were higher than that in the general population.7.Age, male, smoking, waist-to-hip ratio, systolic blood pressure were the common risk factors for reduced eGFR and periodontitis severity in chronic periodontitis patients.8. Age, BMI, systolic blood pressure were common risk factors for periodontitis severity and the occurrence of proteinuria in periodontitis patients.9. Smoking is a common risk factor for periodontitis patients haematuria and affect the severity of periodontitis.10. Low education level was the common risk factor for the occurrence of hematuria and bleeding of gingival inflammation in periodontitis patients.11. Concentrations of CRP, IL-1,IL-6, TNF-a in the serum of chronic periodontitis patients were associated with the incidence of CKD.12.CKD was related to chronic periodontitis, and patients with chronic periodontitis in Han population were high risk group of CKD, so screening for CKD in chronic periodontitis patients was necessary.The results of this study show that the rise and development of periodontal medicine can contribute to advances in the prevention and treatment of other diseases, and will draw increasing attention from the entire field of medicine. In treating periodontitis, as dentists we should consider not only the damages caused by periodontal disease in oral cavity, but also systemic factors of patients’whole body. Based on this study, this research group will further carry out prospective study, queue epidemiological investigation or interventional experiments so as to provide new ideas and methods for the treatment of chronic periodontitis and CKD treatment, and promote collaborative multidisciplinary treatment to achieve the goal of maintaining oral health and enhancing the quality of life. |
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