Oral health in patients with chronic kidney disease : emphasis on periodontitis

Background: Periodontitis is a common bacteria-induced chronic inflammatory disease with mild symptoms. It leads to destruction of the periodontium and finally to tooth loss in a susceptible patient. Periodontitis is associated with many systemic diseases such as diabetes, atherosclerosis, cardiovascular diseases, and chronic kidney disease (CKD) through low-grade systemic inflammation. However, no causality can be drawn. CKD is defined as a deficiency in kidney structure or function lasting over three months. Its prevalence is over 10% globally. The main risk factors of CKD are diabetes mellitus, hypertension, and obesity although periodontitis has been proposed to be a non-traditional risk factor. When CKD is progressed to end-stage renal disease (ESRD), renal replacement therapy (dialysis or kidney transplantation) is needed. Prior to entering kidney transplantation, the candidate must be screened for infections, including oral infections, before immunosuppressive medication can be administered. Patients with ESRD have higher mortality rates compared with general population. Aim and hypotheses: The general aim of this thesis was to examine the oral health of 144 CKD patients with emphasis on periodontal disease; first at predialysis and secondly at post-transplantation stage. Other purposes were to investigate the association between periodontal inflammatory burden and salivary matrix metalloproteinase -8 (MMP-8) concentration, and further, to determine whether oral inflammatory burden associates with mortality. Oral health of diabetic nephropathy patients were compared with other CKD patients. The main hypotheses were that oral health, periodontal disease in particular, is more severe among diabetic nephropathy patients than among other CKD patients. Furthermore, we expected oral health being worse at predialysis compared with post-transplantation stage. Methods: CKD patients were followed up for 157 months (over 13 years). They underwent a full clinical and radiographic oral examination. Salivary samples were collected both at predialysis and post-transplantation stages for detection of MMP-8 by immunofluorometric assay (IFMA). Results: Patients with diabetic nephropathy indeed had worse oral health. Higher salivary MMP-8 concentrations associated with worse oral health at prediaysis stage. The follow-up study showed that the 10-year survival rate of diabetic nephropathy patients was 28% compared to 62% of the other CKD patients. The overall 10-year survival rate was 50%. The most common cause of death was a major cardiovascular event, followed by infection and malignant disease. In the multivariable Cox regression model, older age, diabetic nephropathy diagnosis and having fewer teeth were significant independent risk factors for death. Oral health was better at the follow-up than at the predialysis stage when oral infection treatment had been given. Conclusion: The present results support the existing protocol of the Helsinki University Hospital, where oral examination, accurate diagnosis and proper treatment of oral infection foci are mandatory at the predialysis stage for reducing systemic inflammation among CKD patients. Salivary MMP-8 assessment could help clinical decision making in the future. The association of missing teeth and mortality could be explained by long lasting low grade systemic oral inflammation. Since diabetic nephropathy is associated with poorer oral health, this patient group needs particular attention.