Correlation Between Chronic Periodontitis And Chronic Kidney Disease

Objective: To investigate the correlation between chronic periodontitis(CP)and Chronic Kidney Disease(CKD), cross-sectional survey and follow-up study were conducted to find epidemiological evidence that periodontitis initiate and accelerate the CKD. For further exploring the mechanism of inflammation correlation between periodontitis and CKD, we compared the levels of IL-6, TNF-a, TGF-?, hs-CRP and the distributions of hs-CRP gene polymorphism in patients with periodontitis and CKD among rural Uyghur adults.Methods: The epidemiological study is divided into two phases: cross-sectional survey in 2007 and a longitudinal 6-year follow-up study. At baseline, 1650 subjects were randomly selected using a stratified, multistage sampling among Uyghur adults, 15 villages were selected from 364 villages in Moyu county and110 subjects per village were sampled randomly for the survey.The subjects were sampled from the fifth household census of the district's population by Chinese Center for Disease Control and Prevention(CDC). All subjects completed an questionnaire and had a dental examination as well as physical examination at baseline and follow-up.Blood and urine specimens were assayed for urinary creatinine, microalbuminuria, serum creatinine, serum glucose, hepatitis B virus(HBV)/hepatitis C virus(HCV) and so on.Definition of CKD was according to KDIGO(Kidney Disease: Improving Global Outcomes) guideline.Patients with eGFR<60? ml/min/1.73? m2 or proteinuria positive were repeatedly measured in 3-6 months, and both positive were identified as CKD. To further explore the inflammatory mechanism on correlation between periodontitis and CKD, 181 Uygur subjects with CKD and 197 non-CKD subjects were selected by random sampling from Moyu county in 2013. Inflammation biomarkers were measured,including IL-6, TNF-a, TGF-?, hs-CRP, and hs-CRP gene polymorphisms were analyzed using SNa P shot. Results: A total of 1415 subjects completed the survey in 2007. During follow-up periods, 54 subjects died, 13.6%(193/1415)were lost, 86.4%(1222/1415)of subjects were followed, and 216 could not complete dental examination because ofdental calculus, all teeth loss and fixed dental prostheses, 3 subjects with missing blood and urine specimens, were excluded, thus 952 completed the survey. The mean age of the sample was(39.9±14.8) year-old in 2007 and(45.0±14.4) year-old in 2013. Both of the two surveys were similar to the fifth Moyu census data on gender structure. The investigation showed that the prevalence of chronic periodontitis increased with age,especially severe periodontitis. After adjusting for gender, age, hyperuricemia,hypertension, diabetes, metabolic syndrome, stroke, myocardial infarction and other risk factors, subjects with severe periodontitis had a higher risk for CKD than those without periodontitis(OR=1.8, 95%CI: 1.0 to 3.2). Follow-up study showed that the prevalence of periodontitis increased, especially the moderate and severe periodontitis. After 6 years follow-up, 4.2%(47/1113) subjects developed CKD, the cumulative incidence of CKD was 9.5% in severe periodontitis group, higher than in moderate periodontitis group(2.3%), 0.6% in mild periodontitis and 0.5% in non-periodontitis. Adjusting for the traditional risks of CKD, we found subjects with severe periodontitis had a 4.4 times(95% CI, 2.3-8.4) risk of CKD in comparison with non-periodontitis. In addition,subjects with coexistence of periodontitis and CKD had a higher all-cause mortality(18.8% vs. 6.7%, 4.2%, 0.4%) than those with periodontitis only or CKD only,especially those with neither periodontitis nor CKD. In multivariate logistic regression model, as compared to subjects with neither periodontitis nor CKD, those with severe periodontitis only had increased risk of all-cause mortality(OR2.9, 95%CI:1.5-6.0),coexistence of severe periodontitis and CKD was associated with OR, 5.4(95%CI,1.1-26.2) for all-cause mortality and OR, 2.9(95%CI, 0.8-10.3) for those with CKD only.Cox proportional hazard models revealed that compared to participants with neither periodontitis nor CKD, those with coexistence severe periodontitis and CKD were associated with a four times greater risk of all-cause mortality(HR4.1, 95%CI: 1.4-11.5)and 3.8 times in those with CKD only(95% CI: 1.1-13.3), respectively.In 2013, a randomized controlled trial is designed to compare the levels of inflammatory markers(IL-6, TNF-a, TGF-?, hs-CRP) and the distributions of hs-CRP gene polymorphism betweeen the CKD group and periodontitis group. Among the inflammatory markers,serum hs-CRP levels were higher in CKD group than in non-CKD group. In addition,hs-CRP levels were significantly higher in severe periodontitis group than in mild to moderate periodontitis and non-periodontitis groups. To further research the association between the hs-CRP gene polymorphisms and CKD, genotyping was performed by SNaP-shot assay. Single nucleotide polymorphisms(SNPs) were selected for genotypingin the case-control study: rs1205 and rs2794520.Three genotypes(CC, CT, and TT) were detected in rs1205 and rs2794520. The frequencies of the three genotypes showed a tendency for CT>TT+CC in periodontitis and CKD group compared with periodontitis group(P < 0.05), while genotypes frequency did not show statistically significant difference between the CKD group and healthy controls(P>0.05). Conclusion: Severe periodontitis is the risk factor of CKD, which can accelerate the CKD progression.Besides, there is a strong, association between severe periodontitis and increased mortality in individuals with CKD.The correlation between chronic periodontitis and CKD is associated with the systemic inflammation.There was a significant association between hs-CRP and the extent of periodontitis. Two polymorphisms of hs-CRP gene(rs2794520 and rs1205) may have a close relationship with coexistence CKD and periodontitis in rural Uygur adults.