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  • Review Article
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Interplay between periodontitis and chronic kidney disease

Nature Reviews Nephrology (2024)Cite this article

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Abstract

Periodontitis 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. 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). 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. 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

  • 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.

  • 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.

  • 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.

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

  • 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.

  • 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.

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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.

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Authors and Affiliations

  1. Periodontal Research Group, Institute of Clinical Sciences, University of Birmingham and Birmingham Community Healthcare NHS Foundation Trust, Birmingham, UK

    Iain L. C. Chapple, Josefine Hirschfeld, Thomas Dietrich & Praveen Sharma

  2. NIHR Birmingham Biomedical Research Centre in Inflammation, Birmingham, UK

    Iain L. C. Chapple, Josefine Hirschfeld, Thomas Dietrich & Praveen Sharma

  3. Department of Nephrology, University Hospital Birmingham, Birmingham, UK

    Paul Cockwell

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All 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.

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Glossary

Investing gingiva

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.

Periodontal pocket

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.

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Chapple, I.L.C., Hirschfeld, J., Cockwell, P. et al. Interplay between periodontitis and chronic kidney disease. Nat Rev Nephrol (2024). https://doi.org/10.1038/s41581-024-00910-5

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