Oral health in patients with chronic kidney disease

Chronic kidney disease (CKD) is a complex disorder in which active intervention leads to longer survival expectancy. Oral diseases are complex disorders caused mainly by bacterial, fungal, or viral infections, where primary defense mechanisms are influenced. The most common complications seen in CKD patients are malnutrition, inflammation, and atherosclerosis (MIA syndrome), leading to high morbidity and mortality. Oraldiseases, often asymptomatic, may contribute to a worse prognosis in this patient group. Loss of teeth and inflammation of oral tissues initiate an increasing interest in the effort to describe complicating factors for the MIA syndrome. Oral diseases and consequences of dental treatment are established over a lifetime. By the time an end-stage renal disease appears in old age, the longtime oral health neglect affecting general health can lead to unwanted consequences.

The objective of this thesis is to describe the influence of oral diseases on the medical conditions of CKD patients, to describe possible oral disease acceleration during CKD progression, and to try to explain these phenomena in this specific group of patients. Oral health neglect identified and treated at an early stage of CKD might contribute to slow down development of coronary heart disease, and thus contribute to better prognosis for CKD patients.

Paper I. Oral health is described, comparing CKD patients to controls with normal renal function. We investigated teeth conditions both clinically and with radiographs. We also investigated the loss of attachment on tooth supportive tissues. Inflammatory lesions around teeth apices were investigated, as were mucosal changes. We found that CKD patients were worse affected than their age- and sex-matched controls even after adjusting for a number of confounders.

Paper II. The immune system in CKD-5 patients is affected for a number of reasons. Fungal infections might appear in periods of low primary defense both locally and systemically. An untreated oral fungal infection might influence eating and swallowing and the general health becomes affected. This paper describes the prevalence of oral fungal infections and suggests routines to avoid complications in the care of CKD-5 patients.

Paper III. Hyposalivation becomes a big issue for many CKD patients. The oral health is highly dependent on saliva as one important factor to maintain primary defense mechanisms and protect oral tissues from invading pathogens. The literature has been contradictory in how hyposalivation affects CKD patients. In this paper we show that hyposalivation is affected during CKD, and also describe the profiles of secreted proinflammatory factors of interest. Salivary glands are tissues with a high metabolism, and are affected early due to disturbances of water and electrolyte balance. We found elevated levels of whole salivary proteins and cytokines/chemokines signaling transmigration of leukocytes and resolution of inflammation in CKD patients, as compared to controls.

Paper IV. CKD patients are found to have an increased circulatory DNA oxidative stress. This process is shown to correlate to the MIA syndrome, as it affects endothelial tissues and is one factor in the pathogenesis of cardiovascular disease. This study investigates how accessory gland tissue reacts to this process. We found a correlation between oxidative DNA damage and hyposalivation.

List of scientific papers

I. Thorman R, Neovius M, Hylander B (2009). Clinical findings in oral health during progression of chronic kidney disease to end-stage renal disease in a Swedish population. Scand J Urol Nephrol. 43(2): 154-9.
https://pubmed.ncbi.nlm.nih.gov/18949632

II. Thorman R, Neovius M, Hylander B (2009). Prevalence and early detection of oral fungal infection: a cross-sectional controlled study in a group of Swedish end-stage renal disease patients. Scand J Urol Nephrol. 43(4): 325-30.
https://pubmed.ncbi.nlm.nih.gov/19363743

III. Thorman R, Lundahl J, Lindberg T, Hylander B (2009). Inflammatory cytokines in saliva: early signs of metabolic disorders in chronic renal failure. A controlled cross-sectional study. [Submitted]

IV. Thorman R, Johansson C, Rodhe Y, Möller L, Hylander B (2009). DNA damage in salivary gland tissue in patients with chronic kidney disease, measured by the Comet assay. [Manuscript]