Oxidative stress links periodontal inflammation and renal function.

Praveen Sharma,Irundika H K Dias,Anthony Fenton,Caroline L R Brown,Thomas Dietrich,Iain L Chapple,Mutahir Rahman,Helen R Griffiths,Charles J Ferro,Amneet Sidhu,Paul Cockwell,Brenda Heaton

doi:10.1111/jcpe.13414

Abstract

AimsPatients with chronic kidney disease (CKD) are also susceptible to periodontitis. The causal link between periodontitis and CKD may be mediated via systemic inflammation/oxidative stress. Using structural equation modelling (SEM), this cross‐sectional study aimed to explore the causal relationship between periodontal inflammation (PI) and renal function.Materials and methodsBaseline data on 770 patients with stage 3–5 (pre‐dialysis) CKD from an ongoing cohort study were used. Detailed, bioclinical data on PI and renal function, as well as potential confounders and mediators of the relationship between the two, were collected. SEMs of increasing complexity were created to test the causal assumption that PI affects renal function and vice versa.ResultsStructural equation modelling confirmed the assumption that PI and renal function are causally linked, mediated by systemic oxidative stress. The magnitude of this effect was such that a 10% increase in PI resulted in a 3.0% decrease in renal function and a 10% decrease in renal function resulted in a 25% increase in PI.ConclusionsPeriodontal inflammation represents an occult source of oxidative stress in patients with CKD. Further clinical studies are needed to confirm whether periodontal therapy, as a non‐pharmacological approach to reducing systemic inflammatory/oxidative stress burden, can improve outcomes in CKD.

Highlights

Chronic kidney disease (CKD) affects 8-16% of the global population (Jha et al, 2013) and is strongly associated with premature mortality secondary to cardiovascular disease and progression to end-stage kidney disease
In investigating the path-specific effect of estimated glomerular filtration rate (eGFR) on periodontal inflamed surface area (PISA), there was no clinically or statistically significant effect of eGFR on PISA via any pathway, apart from via the latent variable oxidative stress where a 10% decrease in eGFR led to a 25.0% increase in PISA (95%CI:0.4 to 49.6)
We found a bidirectional, causal relationship between periodontal inflammation and renal function: a 10% increase in PISA led to a 3.0% decrease in eGFR and a 10% decrease in eGFR led to a 25.0% increase in PISA

Summary

Introduction

Chronic kidney disease (CKD) affects 8-16% of the global population (Jha et al, 2013) and is strongly associated with premature mortality secondary to cardiovascular disease and progression to end-stage kidney disease. Prognostic factors associated with worse outcomes in CKD include severity of kidney disease (Go, Chertow, Fan, McCulloch, & Hsu, 2004), systemic inflammation and oxidative stress (Cachofeiro et al, 2008; Small, Coombes, Bennett, Johnson, & Gobe, 2012). Periodontal inflammation is associated with increased systemic inflammatory and oxidative stress (Allen, Matthews, Halloran, Griffiths, & Chapple, 2011; Tonetti & VanDyke, 2013). Periodontitis has been associated with increased all-cause mortality in patients with CKD (Zhang, Jiang, Sun, & Chen, 2017). Periodontitis is associated with worse outcomes in patients with cardiovascular disease (Dietrich, Sharma, Walter, Weston, & Beck, 2013) and diabetes (Sanz et al, 2018). Periodontitis treatment reduces plasma concentrations of pro-inflammatory mediators (D'Aiuto, Orlandi, & Gunsolley, 2013; D'Aiuto et al, 2004; Demmer et al, 2013; Freitas et al, 2012; Teeuw et al, 2014) and, in patients with diabetes, reduces glycated haemoglobin (HbA1C) by 0.27– 0.48% (Sanz et al, 2018)

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