Title: Impact of Successful Periodontal Intervention on Renal and Vascular Systems in patients with Chronic Kidney Disease-A Pilot Interventional Randomised Controlled Trial
Funder: Department of Health and Social Care

Abstract: Background Chronic Kidney DiseaseIn the UK, Chronic Kidney Disease (CKD) affects approximately 13% of the adult population and is associated with high morbidity and mortality. The treatment of CKD represents a significant burden to the healthcare economy. In patients with CKD, the main cause of excess mortality cardiovascular disease (CVD) which is related to the severity of kidney disease and also to an increased systemic inflammatory burden. Hence, biomarkers of systemic inflammation and oxidative stress are reliable indicators of mortality in such patients. Arterial stiffness is increased in patients with CKD and studies show an association between arterial stiffness and CKD progression. Therefore, identifying and targeting modifiable risk factors that contribute to systemic inflammation in CKD patients is an important strategy in reducing morbidity and mortality in these patients. PeriodontitisPeriodontitis is a common chronic inflammatory condition in humans and periodontal inflammation contributes to the systemic inflammatory burden as evidenced by increases in biomarkers of systemic inflammation and oxidative stress in patients with periodontitis. Successful periodontal therapy is associated with reductions in these markers. Therefore, periodontitis may act as a co-morbid chronic inflammatory disease in patients with CKD, contributing to disease progression and mortality and this pathway may be amenable to treatment.Periodontitis and CKD: Research to date by the applicantI have shown that patients with CKD have a greater prevalence and severity of periodontitis (compared to a locally derived control population) and that worsening periodontal health in these patients is associated with decreasing eGFR and increasing arterial stiffness. I have also shown that the presence of periodontitis is associated with a 40% increase in the rate of mortality in patients with CKD. Periodontitis and CKD: Literature review To date, the majority of studies in this field have been cross-sectional in nature, showing (as I have) an increased prevalence of periodontitis in patients with CKD, rather than its impact upon CKD progression and cardiovascular complications. There are currently no randomised controlled trials studies in this area and the two interventional studies that have been conducted in the field cannot be used to inform on changes in renal or cardiovascular health with periodontal treatment. A recent systematic review into the association between periodontitis and CKD concluded with the urgent need for RCTs' in this field. Due to the paucity of literature in this field, pilot studies are needed before large-scale, definitive trials are embarked upon. Research QuestionThe overarching research question which this pilot will contribute to answering is: In patients with Chronic Kidney Disease, does the intensive treatment of periodontitis and subsequent maintenance of periodontal health, compared with the current, community standard of periodontal care, have an effect on renal and cardiovascular health? Plan of investigationThe proposed design for this pilot study is a randomised controlled trial (RCT) using a parallel group RCT design. 100 patients with periodontitis and CKD will be randomised into two arms; 50 to receive intensive periodontal treatment and 50 to act as a control arm. Patients will be followed up for 18 months and data on a range of pilot, feasibility and clinical outcomes will be collected. Impact If this pilot study provides encouraging results, a larger, definitive study will follow. If that shows that periodontal therapy confers a systemic health benefit in patients with CKD, this could provide a simple and cost-effective intervention to reduce morbidity and mortality in such patients. The next stage would include developing a care pathway for CKD patients that involves establishing a network of dental hygienists to deliver such therapy in a primary care setting.

Lay abstract: Patients with Chronic Kidney Disease (CKD) may also have a common, bacterial inflammatory condition affecting the gums (periodontitis). The harmful effects of this inflammation spread to the rest of the body via the blood stream. I propose a pilot study to assess the practicality of a larger trial into the effects of improving periodontal health on the general health of patients with CKD. This will be achieved by comparing patients who receive thorough periodontal treatment with those that don't. If treating periodontitis in patients with CKD improves their health, this may be an inexpensive and safe treatment for such patients.

Research activity codes: 6.1 PHARMACEUTICALS;6.4 SURGERY
Health categories: RENAL AND UROGENITAL