Evaluation of monocyte chemotactic protein (MCP-1) in saliva as an early sign of metabolic disorders in patients with chronic kidney disease
Research Abstract
Summary
The oral health is a mirror of the systemic health of the human body, systemic diseases may be affected by the oral health or give oral manifestations and sometimes oral manifestations may be the early signs of the systemic disease. Chronic kidney disease is one of the systemic diseases accompanied by worsen oral and periodontal condition. A bidirectional relation will result in further deterioration of the renal disease due to the neglected oral hygiene. (Fisher et al. 2011).
There are many mechanisms by which chronic kidney disease can affect the oral cavity; uremia, hyperparathyroid hormone, anemia, oxidative stress and and the dramatic rise in inflammatory mediators such as IL-1, IL-6,TNF-α, CRP and MCP-1(Thorman et al. 2010). The oral mucosa, salivary glands, teeth and even periodontal tissues all are affected by the disease (Sunil et al. 2012).
Complications of chronic kidney disease could be prevented if the condition was early detected and controlled; metabolic complications and cardiovascular complication are the most serious complications of chronic kidney disease (Levey et al. 2011); both can be early detected and controlled. One successful approach to control the complications is to monitor the inflammatory mediators such as MCP-1(Thorman et al. 2010) a key chemokine; its increasing level translates the decline in renal function (Murea et al. 2012) and predates the onset of its serious complications (Nishi et al. 2011).
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Saliva is a noninvasive successful diagnostic method that can be used to diagnose and monitor many systemic diseases. The salivary composition and volume can predict many diseases and reflect the systemic condition. Almost all disease markers detected in serum or urine are also detectable in saliva (Sebastien et al. 2010). Salivary changes in chronic kidney disease are due to increased concentration of urea, hyposalivation, hyperphosphatemia, increased inflammatory mediators and oxidative stress (Vahedi et al. 2012). MCP-1 in saliva not only predicts the complications of chronic kidney disease but also jeopardizes the periodontal health (Gupta et al. 2013).
The aim of the present study was to evaluate the levels of pro-inflammatory cytokines (MCP-1) a biomarker in secreted stimulated saliva of patients with CKD as an early sign of metabolic disorder for those patients and its effect on their oral condition.
The current study was conducted on 50 individuals, selected from the outpatients’ clinic in the oral medicine and periodontology department, Faculty of oral and dental medicine, the chronic kidney disease clinic outpatients, and the nephrology department inpatients, Faculty of medicine, Cairo University Hospital. They were divided into 4 groups as follow:
Group 1: consists of fifteen patients with a GFR 59-30 ml/min/1.73 m2 “Stage3”.
Group 2: consists of fifteen Patients with a GFR 29-15 ml/min/1.73 m2 “Stage 4”.
Group 3: diseased control group, consists of ten individuals with chronic moderate to severe periodontitis, these patients were selected to be medically free.
Group 4: control group, consists of ten individuals, these patients were selected to be medically free.
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Patients were subjected to full history taking, full clinical examination to oral and dental tissues including examination of the oral mucosa, plaque index, gingival index, and clinical attachment level for evaluation of the periodontal condition and stimulated salivary sample collection for evaluation of MCP-1 and evaluation of the salivary flow rate.
Quantitative data were presented as mean and standard deviation (SD) values. Data were explored for normality using Kolmogorov-Smirnov and Shapiro-Wilk tests. Age, salivary flow rate, MCP-1 levels and CAL data showed parametric distribution while DMFT index and its components, GI and PI data showed non-parametric distribution.
In the present study GFR values were used to describe the decline in renal function in the two CKD stages. MCP-1 values were compared to GFR in different CKD stages in salivary samples; the results showed that salivary MCP-1 values are inversely proportional to the GFR values. Salivary MCP-1 values were statistically correlated to all other parameters in this study; age, salivary flow, DMFT, GI, PI and CAL. The results have shown that a direct proportional relation was found between MCP-1 and age, M score (number of missing teeth), DMFT, GI, PI, CAL. An inverse proportional relation was found between MCP-1 and D score (number of decayed teeth), F score (number of filled teeth) and salivary flow rate.
The results of this study were as follow:
The salivary MCP-1 values were higher in stage 4 CKD or the late stage (464± 84.7 pg/ ml), followed by stage 3 CKD or the early stage (273.5± 42.1 pg/ ml), the chronic periodontitis group (147.5± 20.9 pg/ ml) and the healthy control group (114.3± 8.2 pg/ml).
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A relatively decreased salivary flow rate was found in stage 4 CKD which was (0.8± 0.06 ml/ min) and stage 3 CKD which was (1.4± 0.4 ml/ min). The decreased salivary flow rate was significant in both groups compared to the control groups as the chronic periodontitis group was (1.9± 0.1 ml/ min) and the healthy control group was (2.1± 0.1 ml/ min). An inversely proportional relation was found between the salivary flow rate and salivary MCP-1 values.
Periodontal disease was higher in stage 4 CKD patients. The gingival index percentage; stage 4 CKD had the significantly higher percentage of surfaces with moderate to severe gingival inflammation (95%), compared to the chronic periodontitis group (89.5%), and healthy control group (0%). Stage 3 CKD was (82.7%), the percentage was significantly lower than stage 4 CKD and chronic periodontitis group but was significantly higher than the healthy control group.
The plaque index results showed that the percentage of teeth surfaces with moderate to severe plaque accumulation was significantly higher in stage 4 CKD (94.9%), compared to the chronic periodontitis group (87.6%) and the healthy control group (0%). Stage 3 CKD was (86.6%) the value was significantly lower than stage 4 CKD and not significantly lower than the chronic periodontitis group but was significantly higher than the healthy control group.
The clinical attachment level results showed that the percentage of surfaces with moderate to severe periodontitis was (87.6%), compared to chronic periodontitis group which was (81.6%) and healthy subjects (0%) despite the fact that the stage 4 CKD patients had lower number of remaining teeth in relation to all other study groups. Stage 3 was (53.9%) and it was significantly lower
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comparing the results to stage 4 CKD and the chronic periodontitis group but was significantly higher than the healthy control group.
Chronic kidney disease patients in stage 4 had the higher DMFT (24.4± 4.5), followed by chronic periodontitis group (20.7± 4.3). The healthy control group was next (15.9± 3), followed by the early CKD stage (14.1± 6.4).
Research Keywords
Evaluation of monocyte chemotactic protein (MCP-1) in saliva as an early sign of metabolic disorders in patients with chronic kidney disease