AbstractPeriodontitis is a ubiquitous chronic inflammatory disease affecting the supporting tissues of the teeth and is a major cause of multiple tooth loss. Despite being preventable, periodontitis and dental caries are responsible for more years lost to disability than any other human condition. The most severe form of periodontitis affects 1 billion individuals, and its prevalence is increasing globally.

摘要牙周炎是一种普遍存在的慢性炎症性疾病，影响牙齿的支持组织，是多发性牙齿脱落的主要原因。尽管牙周炎和龋齿是可以预防的，但与其他任何人类疾病相比，牙周炎和龋齿是导致残疾损失更多年的原因。最严重的牙周炎影响了10亿人，其患病率在全球范围内正在增加。

Periodontitis arises from a dysregulated and hyperactive inflammatory response to dysbiosis in the periodontal microbiome. This response has systemic effects associated with premature mortality and elevated risk of several systemic non-communicable diseases (NCDs), including atheromatous cardiovascular disease, type 2 diabetes and chronic kidney disease (CKD).

牙周炎是由牙周微生物组中对生态失调的失调和过度活跃的炎症反应引起的。这种反应具有与过早死亡和几种全身性非传染性疾病（NCD）风险升高相关的全身性影响，包括动脉粥样硬化性心血管疾病，2型糖尿病和慢性肾病（CKD）。

This risk association between periodontitis and NCDs is independent of their shared common risk factors, suggesting that periodontitis is a non-traditional risk factor for NCDs such as CKD. As periodontitis progresses, the immune cells and mediators underpinning its pathophysiology leak into the systemic circulation through the ulcerated oral mucosal lining, inducing in a systemic inflammatory profile that closely mirrors that observed in patients with CKD.

牙周炎和非传染性疾病之间的这种风险关联与其共同的危险因素无关，这表明牙周炎是CKD等非传染性疾病的非传统危险因素。随着牙周炎的进展，支持其病理生理学的免疫细胞和介质通过溃疡的口腔粘膜衬里渗入体循环，诱导全身炎症反应，这与CKD患者的观察结果非常相似。

The relationship between periodontitis and CKD seems to be bi-directional, but large-scale intervention studies are required to clarify causality and could lead to new care pathways for managing each condition as an exposure for the other.Key points.

牙周炎和CKD之间的关系似乎是双向的，但需要进行大规模的干预研究来阐明因果关系，并可能导致新的护理途径来管理每种疾病作为另一种疾病的暴露。关键点。

Periodontitis is a ubiquitous chronic inflammatory non-communicable disease (NCD) and the most common cause of multiple tooth loss in humans. Alongside dental caries, periodontitis is responsible for more years lost to disability than any other human disease.

牙周炎是一种普遍存在的慢性炎症性非传染性疾病（NCD），也是人类多发性牙齿脱落的最常见原因。除了龋齿，牙周炎比任何其他人类疾病都要导致更多的残疾。

Periodontitis shares common risk factors with other NCDs but is also an independent risk factor for type 2 diabetes mellitus, atherogenic cardiovascular disease and chronic kidney disease (CKD), amongst other NCDs.

牙周炎与其他非传染性疾病有共同的危险因素，但也是2型糖尿病，致动脉粥样硬化性心血管疾病和慢性肾病（CKD）以及其他非传染性疾病的独立危险因素。

Periodontitis arises from a dysregulated and hyperactive immune-inflammatory response to dysbiosis within the periodontal microbiome. These responses cause local injury that leads to the release of inflammatory mediators and pathogenic bacteria into the vasculature, with systemic effects that can affect distant organs..

牙周炎是由牙周微生物组内对生态失调的失调和过度活跃的免疫炎症反应引起的。这些反应会导致局部损伤，导致炎症介质和病原菌释放到脉管系统中，并产生可能影响远处器官的全身作用。。

Several studies suggest a bidirectional causal relationship between periodontitis and CKD, with systemic oxidative stress being identified as an important mediator.

一些研究表明牙周炎和CKD之间存在双向因果关系，全身氧化应激被确定为重要的介质。

Immune cell hyper-activity and -reactivity is a feature of periodontitis. Among innate immune cells of myeloid lineage (predominantly neutrophils), persistent hyperreactivity is likely driven by maladaptive innate immune training. Clonal haematopoiesis of indeterminate potential in older individuals might be another source of pro-inflammatory cells that contribute to the bidirectional link between periodontitis and CKD..

免疫细胞高活性和高反应性是牙周炎的一个特征。在骨髓谱系的先天免疫细胞（主要是中性粒细胞）中，持续的高反应性可能是由适应不良的先天免疫训练驱动的。老年人不确定潜能的克隆性造血可能是促炎细胞的另一个来源，这有助于牙周炎和CKD之间的双向联系。。

Large-scale intervention studies are needed to examine the causal nature of the relationship between periodontitis and CKD definitively, and could lead to novel therapeutic strategies.

需要大规模的干预研究来明确检查牙周炎和CKD之间关系的因果关系，并可能导致新的治疗策略。

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Fig. 1: Influence of periodontitis and diabetes on CKD survival.Fig. 2: Progression from pristine health to periodontitis.Fig. 3: Potential causal pathways linking periodontal disease and kidney dysfunction.Fig. 4: Biologically plausible mechanisms underlying the interplay between periodontitis and CKD..

图1：牙周炎和糖尿病对CKD存活的影响。图2：从原始健康到牙周炎的进展。图3：连接牙周病和肾功能障碍的潜在因果途径。图4：牙周炎和CKD之间相互作用的生物学合理机制。。

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(Quintessence Publishing, 2022).Download referencesAuthor informationAuthors and AffiliationsPeriodontal Research Group, Institute of Clinical Sciences, University of Birmingham and Birmingham Community Healthcare NHS Foundation Trust, Birmingham, UKIain L. C. Chapple, Josefine Hirschfeld, Thomas Dietrich & Praveen SharmaNIHR Birmingham Biomedical Research Centre in Inflammation, Birmingham, UKIain L.

（精粹出版社，2022年）。下载参考文献作者信息作者和附属机构伯明翰大学临床科学研究所和伯明翰社区医疗保健NHS基金会信托基金会，伯明翰，UKIain L.C.Chapple，Josefine Hirschfeld，Thomas Dietrich＆Praveen SharmaNIHR伯明翰炎症生物医学研究中心，伯明翰，UKIain L。

C. Chapple, Josefine Hirschfeld, Thomas Dietrich & Praveen SharmaDepartment of Nephrology, University Hospital Birmingham, Birmingham, UKPaul CockwellAuthorsIain L. C. ChappleView author publicationsYou can also search for this author in.

C、 Chapple，Josefine Hirschfeld，Thomas Dietrich＆Praveen SharmaDepartment of Nephrology，University Hospital Birmingham，Birmingham，UKPaul CockwellAuthorsIain L.C.ChappleView author Publications您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsAll authors researched data for the article and wrote the manuscript. I.L.C.C., P.C., T.D. and P.S. made substantial contributions to discussions of the content. I.L.C.C., J.H., P.C. and P.S. reviewed or edited the manuscript before submission.Corresponding authorCorrespondence to.

PubMed谷歌学术贡献所有作者都研究了文章的数据并撰写了手稿。一、 L.C.C.，P.C.，T.D.和P.S.对内容的讨论做出了重大贡献。一、 。对应作者对应。

Iain L. C. Chapple.Ethics declarations

伊恩·L·C·查普尔。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Peer review

同行评审

Peer review information

同行评审信息

Nature Reviews Nephrology thanks Kazuhiko Nakano and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

《自然评论肾脏病学》感谢Kazuhiko Nakano和另一位匿名审稿人对这项工作的同行评审做出的贡献。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.GlossaryInvesting gingiva

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。舌诊牙龈

Specialized mucosal tissue comprising a stromal core with an orthokeratinized stratified squamous epithelial surface that covers and attaches to the alveolar process of the jaw bones.

特殊的粘膜组织，包括基质核心，具有角化的层状鳞状上皮表面，覆盖并附着于颌骨的肺泡过程。

Periodontal pocket

牙周袋

Pathologically deepened gingival crevice arising owing to apical migration of the junctional epithelial attachment to the enamel of the tooth and in response to dental plaque-induced loss of the periodontal connective tissue attachment to the root and alveolar bone loss.

由于连接上皮附着于牙齿牙釉质的顶端迁移以及牙菌斑引起的牙周结缔组织附着于牙根的损失和牙槽骨损失，导致牙龈缝隙病理性加深。

Rights and permissionsSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleChapple, I.L.C., Hirschfeld, J., Cockwell, P.

权利和许可Pringer Nature或其许可人（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Chapple，I.L.C.，Hirschfeld，J.，Cockwell，P。

et al. Interplay between periodontitis and chronic kidney disease..

牙周炎和慢性肾脏疾病之间的相互作用。。

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