There may be a bidirectional relationship between ESRD and chronic periodontitis. In ESRD patients receiving HD and/or PD are easier to suffer from the microvascular disease, atherosclerosis, systemic inflammation, malnutrition, and chronic periodontitis [12]. CP is a chronic immunoinflammatory disease which is caused by main gram-negative bacteria that destroys the supporting tissues of the teeth and, if left untreated, eventually results in tooth loss [29]. Local periodontal infections may lead to the systemic burden of inflammatory mediators and aggravate the existing metabolic, endocrine and immune disorders in patients receiving HD and/or PD. The presence of periodontitis is associated with high levels of hs-CRP and protein consumption [6, 30]. Thus, periodontitis may be a potential risk factor of systemic inflammation and malnutrition in ESRD patients [19]. PT is the basis of periodontal treatment and the feasible and easily accessible method to control infection of periodontal disease. Recently, the control of systemic inflammation and nutritional status through PT in ESRD patients has aroused the interest of clinicians and researchers. However, current evidence showed that the results of the effects of PT on systemic inflammation and metabolic status in these affected patients were inconsistent. This inconsistency is not conducive to the clinical application of PT, the control of systematic inflammation and improvement of metabolism in patients receiving HD and/or PD. Hence, it is imperative to perform this systematic review to determine whether the effect of PT on reducing serum inflammation levels and improving metabolic status in dialysis patients with CP through published RCT evidence.
Relevant inflammatory and metabolic markers played a crucial role in the pathological process and diagnosis of dialysis patients [13, 31]. This systematic review described 3 serum inflammation markers: hs-CRP, IL-6, and/or TNF-α. Hs-CRP is an acute-phase protein produced only by the liver and is considered diagnostic and prognostic markers of inflammatory diseases. As we all know, hs-CRP has been considered to be independent predictors of death in dialysis patients [32]. Hs-CRP can promote the secretion of IL-6. IL-6 is a peptide medium synthesized by a variety of cell types, including T cells, fibroblasts, epithelial cells, and endothelial cells, which mainly work in the immune and inflammatory response [17]. The levels of IL-6 and hs-CRP in dialysis patients have been demonstrated to be higher than those in systemic healthy patients with periodontitis. Additionally, studies have shown that CP is associated with elevated serum hs-CR and IL-6 [33]. Researchers have focused on exploring whether a decline of serum inflammatory factors levels after PT in dialysis patients. On the bias of the existing evidence, we perform two separate meta-analyses for hs-CRP and IL – 6 through PT in ESRD patients with periodontitis. Besides, the inflammation was qualitatively evaluated by the TNF-a level. In our study, the included studies ranged from 4 weeks, 6weeks, 8 weeks, 3 months and 6 months evaluation periods for hs-CRP. The duration of the intervention of 4 studies varied from 4 weeks to 2 months, so we perform subgroup analysis by follow-up period in less than or equal to 2 months, at 3 months and 6 months. A subgroup analysis by follow-up time verified a significant reduction in the level of hS-CRP, suggesting a reduction in systemic inflammation after PT in dialysis patients with periodontitis. The level of IL-6 showed a trend towards a decrease following PT, however, the level of serum IL – 6 in the PT group had no statistically significant reduction than the control group. Although the results of these three markers revealed that the reducing levels of inflammation in dialysis patients, only the hs-CRP level was statistically significant. We think these different results may be due to the small size and a limited number of studies, meaning larger scale and more clinical intervention trials are required in the future.
To assess the metabolic markers more comprehensively in dialysis patients, we also evaluated nutrition (albumin, Alb) and lipid metabolic markers (TC, TG, HDL-C, LDL-C). Fang and colleagues showed that the PT achieved a greater increase in lipid metabolic markers than no treatment while no significant differences were found. Regarding Alb markers, two of the included studies compared the Alb parameter. One of the included studies evaluated Alb after 6 weeks, 3 months and 6 months, whereas the other one’ s Alb changes had been reported after a 3-month and 6-month study period. Thus, further studies with longer follow-up are needed to elucidate the effects of the PT on serum Alb maker. So we perform subgroup analyses by follow-up periods while no significant differences were found. Wehmeyer and colleagues showed that the PT achieved a greater increase in Alb markers than no treatment while no significant differences were found. Fang and colleagues found that the PT achieved a significant reduction in Alb. Previous studies reported that a negative correlation between serum inflammatory and nutrition markers, so the results demonstrated improvement in the nutritional parameter. Since PT can achieve better inflammation markers, more Alb level increase can be gained after PT in patients receiving HD and/or PD.
In the present meta-analysis, we observed substantial heterogeneity for the combined SMD of serum biochemical markers after PD in ESRD patients undergoing dialysis. As we know, heterogeneity in clinical research is inevitable. Biochemical markers are associated with the common risk factors of CP and ESRD, including demographic data for the ESRD subjects with or without diabetes, dialysis types, dialysis time, PT with or without auxiliary use of antibiotics and different follow-up times contributed predominantly to the observed heterogeneity. Considering limited studies, we would have not conducted subgroup analyses by these confounders. Thus, it should be remembered that our conclusions are based on limited studies, and therefore needs to be confirmed by more large and well-designed studies.
This is the first systematic review and meta-analysis to analyze the effect on systemic inflammation and metabolic measures after PT for the treatment of periodontitis in HD or/and PD patients. Four of 5 included RCTs were published within the past four years. Thus, the results of this study are reliable. In this study, we quantitatively assessed the systematic inflammation markers and nutrition markers, and the results found potential advantages of serum inflammation markers and biochemical measures after PT in dialysis patients with CP. Simultaneously, several limitations were identified in our systematic review. First, PT, as a traditional technique for the treatment of periodontitis, lacks sufficient original clinical trials in chronic renal diseases, especially HD and/or PD patients with CP, so only 5 articles were included. Second, the heterogeneity noticed among the selected studies is a possible limitation of this study, which is associated with the presence of confounding factors, such as demographic data for the subjects with or without diabetes, dialysis types, dialysis time and different follow-up times. Third, all of the included articles were evaluated as moderate-risk bias. Finally, we did not perform the evaluation of publication bias and sensitivity analyses for a small number of papers. Additionally, we qualitatively analyzed the TNF-a level and lipid metabolic markers since the included studies provided limited information. Considering the above limitations, the effects on serum clinical and biochemical markers after PT for the treatment of periodontitis remain worthy of investigation.
A few studies have evaluated the effect of non-operative periodontal therapy on inflammatory markers in this population. We need a large number of studies to assess the benefits of periodontal treatment in patients undergoing HD and/or PD. Further well-design of studies is needed to provide robust evidence regarding the systematic effects of PT in ESRD patients undergoing HD and/or PD. A longer evaluation time may produce more comparable results when studying clinical parameters of periodontitis.