基于横断面数据的慢性肾病与牙周炎相关性分析及致病机制探究

Correlation and mechanism between chronic kidney disease and periodontitis based on cross-sectional data

目的探讨成年人慢性肾病与牙周炎是否存在相关性,以及两种疾病的潜在致病机制。方法下载美国国家健康和营养检查调查数据库(NHANES)1999-2014年慢性肾病与牙周炎相关调查资料数据,筛选出患有慢性肾病或牙周炎的对象,针对人口学和临床检验指标,采用加权的单因素和多因素Logistic回归分析,探讨慢性肾病与牙周炎的危险因素相关性。用公开的慢性肾病与牙周炎全基因组关联研究(GWAS)汇总数据集为结局变量,以OPEN GWAS数据库中731种免疫细胞表型和91种炎症蛋白为暴露因素,运用逆方差加权法进行两样本孟德尔随机化(TSMR)分析。结果性别、年龄、种族、教育水平、婚姻状况、收入和健康等7项人口学指标与慢性肾病和牙周炎的发病率有关,其中高龄(≥60岁)、贫困(贫困收入比<1.3)、离婚或丧偶、男性比例在慢性肾病与牙周炎共病组[分别为67.12%(833/1241)、36.83%(457/1241)、34.41%(427/1241)和57.78%(717/1241)]均显著高于非共病组[分别为23.71%(4179/17623)、29.17%(5141/17623)、18.16%(3200/17623)和48.73%(8587/17623)](均P<0.001),高学历(大学及以上)、自评健康状况为极好者在共病组占比较少[分别为14.10%(175/1241)、8.22%(102/1241)]。肾功能检测指标存在异常的人群(包括肾小球滤过率、尿蛋白/肌酐比值、血肌酐、血尿酸、血尿素氮)牙周炎患病率上升。单因素Logistic回归分析显示,牙周炎与慢性肾病的发病率呈显著正相关[优势比(OR)=2.14,95%置信区间(95%CI)为1.90~2.42,P<0.001],多因素Logistic回归分析也显示,慢性肾病与牙周炎互为潜在风险因素(牙周炎对慢性肾病:OR=1.22,95%CI为1.07~1.40,P=0.004;慢性肾病对牙周炎:OR=1.19,95%CI为1.04~1.37,P=0.012);根据人口学指标对模型进行调整后,慢性肾病与牙周炎仍存在显著相关性(P=0.010)。在机制上,TSMR分析结果支持慢性肾病与牙周炎之间存在免疫细胞介导的共同风险因素,即CD64在多种单核细胞上的表达介导慢性肾病和慢性牙周炎的发生,CD64+单核细胞是关键的调控细胞。结论慢性肾病与牙周炎的发病率呈正相关,两者共同的发病机制涉及循环系统中CD64+单核细胞,可针对CD64分子或单核细胞亚群开展有针对性的疾病干预。

ObjectiveTo explore the correlation between periodontitis(PD)and chronic kidney disease(CKD)in adults,as well as the potential mechanisms involved.MethodsData on PD and CKD from the National Health and Nutrition Examination Survey(NHANES)database between 1999 and 2014 were downloaded.Weighted univariate and multivariate logistic regression analyses were conducted to investigate the risk factors associated with PD and CKD,considering demographic and clinical indicators.Using publicly available genome-wide association study(GWAS)summary datasets for CKD and PD as outcome variables,as well as 731 immune cell phenotypes and 91 inflammatory proteins as exposure factors from the OPEN GWAS database,a two-sample Mendelian randomization(TSMR)analysis was performed using the inverse-variance weighted(IVW)method.ResultsSeven demographic indicators including gender,age,race,education level,marital status,income,and health are related to the incidence of CKD and PD.Among them,the elderly(≥60 years old),poverty(poverty-income ratio<1.3),divorce or widowhood,and male ratio in the comorbidity group of CKD and PD[67.12%(833/1241),36.83%(457/1241),34.41%(427/1241),and 57.78%(717/1241)respectively]were significantly higher than those in the control group[23.71%(4179/17623),29.17%(5141/17623),18.16%(3200/17623),and 48.73%(8587/17623)respectively](all P<0.001).Those with high educational level(university and above)and self-rated excellent health accounted for a relatively small proportion in the comorbidity group[14.10%(175/1241)and 8.22%(102/1241)respectively].The prevalence of PD increased among individuals with abnormal renal function indices,including glomerular filtration rate,urine protein/creatinine ratio,serum creatinine,serum uric acid,and blood urea nitrogen.Univariate logistic regression analysis showed a positive correlation between the incidence of PD and CKD(OR=2.14,95%CI:1.90-2.42,P<0.001).Multivariate logistic regression analysis also indicated that PD and CKD were potential risk factors for each other(PD for CKD:OR=1.22,95%CI:1.07-1.40,P=0.004;CKD for PD:OR=1.19,95%CI:1.04-1.37,P=0.012).Furthermore,after adjusting the model based on demographic indicators,there was still a significant correlation between PD and CKD(P=0.010).Mechanistically,the results of the TSMR analysis support the existence of a common risk factor mediated by immune cells between CKD and PD,namely the expression of CD64 on multiple innate immune cells mediates the occurrence of CKD and PD.The absolute count of CD64+monocytes is associated with an increased risk for both CKD(HR=1.11)and PD(HR=1.07),while same tendency showed in the absolute count of CD64+neutrophils for CKD(HR=1.22)and PD(HR=1.23).ConclusionsThere is a positive correlation between CKD and PD,particularly moderate to severe PD,and the shared pathogenesis involves CD64+monocytes in the circulatory system.Targeted interventions focusing on CD64 molecules or monocyte subsets may be beneficial.