Int Urol Nephrol DOI 10.1007/s11255-014-0716-z
NEPHROLOGY - ORIGINAL PAPER
An ignored cause of inflammation in patients undergoing continuous ambulatory peritoneal dialysis: periodontal problems Ismail Kocyigit • Hasan Esat Yucel • Omer Cakmak • Fatma Dogruel • Du¨rdane Banu Durukan • Hafsa Korkar • Aydin Unal • Murat Hayri Sipahioglu Oktay Oymak • Cem A. Gurgan • Bulent Tokgoz
•
Received: 28 January 2014 / Accepted: 8 April 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract Aim We aimed to assess whether there is a significant relation between periodontal health status and inflammation in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and also to reveal the efficiency of periodontal treatment in patients with various degrees of periodontal problems. Patients and methods Overall, 68 patients undergoing CAPD were included in the study. Clinical indices and measurements were obtained at baseline and panoramic radiographies were used for the diagnosis. According to the baseline values, patients were stratified into four groups according to the severity of periodontal problems as follows: healthy/gingivitis, slight-to-moderate, and severe periodontitis. A control examination was performed 3 months after the periodontal treatment for only 43 patients. Clinical and laboratory parameters before and after treatment were compared.
I. Kocyigit (&) A. Unal M. H. Sipahioglu O. Oymak B. Tokgoz Department of Nephrology, Erciyes University Medical Faculty, 38039 Kayseri, Turkey e-mail: [email protected] H. E. Yucel H. Korkar Department of Internal Medicine, Erciyes University Medical Faculty, Kayseri, Turkey O. Cakmak D. B. Durukan C. A. Gurgan Department of Periodontology, Erciyes University Faculty of Dentistry, Kayseri, Turkey F. Dogruel Department of Internal Medicine, Erciyes University Faculty of Dentistry, Kayseri, Turkey
Results The frequency of periodontal disease was found to be high in uremic patients on CAPD. The frequency and severity of periodontitis was also found to be significantly (p \ 0.01) higher in patients with high sensitive C-reactive protein levels and longer duration of peritoneal dialysis (p \ 0.01). In addition, the periodontitis rate was found to be higher in patients with cardiovascular disease (p \ 0.05) and diabetes mellitus (p \ 0.01). Conclusion A meticulous periodontal examination should be a routine part of management of the uremic patients on CAPD because periodontal disease could be one of the hidden sources of unexplained inflammatory status. Keywords Continuous ambulatory peritoneal dialysis Periodontal disease Inflammation
Introduction One of the most important goals in patients with chronic renal disease is to improve their quality of life [1]. Periodontal disease or periodontitis is an inflammatory disease of the gingiva and tissues surrounding teeth due to infectious reasons, which may lead to progressive loss of the supportive tissues of the teeth and consequently to alveolar bone loss. The severity of the disease is determined by the inflammatory response of the body [2, 3]. In addition, periodontitis is associated with disorders that pointed out systemic inflammation. The most remarkable example of this is the relationship between periodontal disease and cardiovascular diseases (CVD) such as atherosclerosis, myocardial infarction, and stroke [4, 5]. Oral hygiene and frequency of periodontal disease have become important issues in chronic renal disease patients. Thus, early assessment of oral health is important to decrease the risk of potential oral cavity infections [6].
123
Int Urol Nephrol
Periodontal health was found to be poor in continuous ambulatory peritoneal dialysis (CAPD) patients, and this inflammatory status was related with markers of malnutrition, inflammation, and atherosclerosis [7]. The prevalence of atherosclerotic complications (myocardial infarction, stroke, and sudden death) is increased in end-stage renal disease (ESRD) patients, especially in hemodialysis patients. Increasing evidence suggests that both in the general population and in dialysis patients, systemic inflammation plays an important role in the pathogenesis of atherosclerotic complications. In the general population, also, evidence shows that moderate to severe periodontitis can contribute to inflammatory burden by increasing highly sensitive C-reactive protein (hs-CRP) levels [8], the most important acute phase protein, which is monitored as a systemic marker of inflammation and also of endothelial dysfunction it is also used as an initial predictor of atherosclerotic events, and may contribute to the increase in the prevalence of atherosclerotic events. Moreover, the results of interventional studies reveal that effective phase I (non-surgical treatment) periodontal therapy may decrease serum hs-CRP levels [8, 9]. Considering that moderate to severe periodontal diseases have a higher prevalence in chronic kidney disease (CKD) and in dialysis populations [3, 10, 11], chronic and generalized periodontitis might be an ignored source of systemic inflammation in ESRD patients and may add to the chronic inflammatory status in CKD. According to very recently published systematic reviews, there is quite consistent evidence to support the positive association between periodontitis and CKD, as well as the positive effect of periodontal treatment on the estimated glomerular filtration rate [12]. There is a presence of strong evidence linking periodontitis with CVD in addition to CKD where improving patients’ oral health could possibly reduce CVD and CKD risks [13]. The main aim of our study was to evaluate the severity and extent of periodontal disease in patients undergoing CAPD. A secondary aim was to detect the changes in inflammatory status by providing appropriate treatment in cases with periodontal disease and finally to determine the association with other comorbidities such as diabetes mellitus (DM) and CVD.
Materials and methods This study was conducted in patients undergoing CAPD managed in the outpatient clinic for peritoneal dialysis at the Erciyes University School of Medicine between August 2012 and April 2013. The dental and periodontal examinations were performed by a periodontologist in the Department of Periodontology of the Faculty of Dentistry at Erciyes University.
123
Inclusion criteria were as follows: 1. 2. 3.
Presence of C15 natural teeth. Year of age C18. Undergoing peritoneal dialysis. Exclusion criteria were as follows:
1.
2. 3.
History of antibiotic therapy within the previous 6 months (including peritonitis treatment) and antiinflammatory drugs within the previous 3 months. Pregnancy or use of contraceptives or any other hormone therapy. Periodontal treatment within the previous 12 months.
Patients were informed about the tests and test methodology that would be used and about potential adverse effects. All patients gave their written consent for the test and physical examination. Also, all volunteer patients were informed about the aim and methods of this study and gave their written consent to participate. This study was conducted in full accordance with the applicable ethical principles, including the World Medical Association Declaration of Helsinki, and was independently reviewed and approved by the Ethical Committee in the Faculty of Medicine. In our center, 175 patients, of whom 155 (89 %) are treated with PD, are currently being followed. Among those treated with PD, 72 who were found to be suitable according to the inclusion/exclusion criteria were referred to the Faculty of Dentistry for diagnosis and treatment. Overall, 68 volunteer patients were included in the study and control visits were performed 3 months after the periodontal treatment. Enrolled patients were evaluated in terms of systemic inflammation and peritonitis both at baseline and at the control visit. None of the patients had any signs of systemic infection. The evaluated signs and symptoms of systemic infection were abdominal, nape, back and forehead pain, fever, nausea, vomiting, diarrhea, dysuria, cough, or rash. In addition to these symptoms, pain, fever, pus, redness, and swelling at the affected area were evaluated as the symptoms of local infection. A history of plaque based on coronary angiography, percutaneous transluminal coronary angioplasty (PTCA), or coronary bypass was accepted as CVD. In all the patients included, the following parameters were evaluated: periodontal clinical measurements and indices, and panoramic X-ray examinations. Periodontal parameters The following clinical parameters were evaluated both at the baseline and third month following the periodontal treatment:
Int Urol Nephrol
The indices used for the evaluation of oral health status were as follows: Plaque index (PI) [14]; presence of bacterial plaque on tooth/root surface. Plaque index scoring was as follows: 1. 2.
3.
4.
No plaque at gingival area in tooth. Presence of plaque which is not macroscopically visible at free gingival margin and tooth surface adjacent to gingival margin but appears as a film at the tip of probe, when probe is moved through orifice of gingival sulcus. Gingival area and tooth surface adjacent to gingival margin are coated by plaque with mild to moderate thickness and plaque is macroscopically visible. Presence of intense soft tissue attachment or plaque at gingival pocket and tooth surface adjacent to gingival edge.
Gingival index (GI) [14]; presence of bleeding at the marginal gingiva. Scoring was as follows: 1. 2.
3.
4.
There is no inflammation sign in marginal gingival. Gingiva is healthy. There is mild discoloration and edema at gingiva. No bleeding occurs during probing. There is mild inflammation. Gingiva is bright, edematous, and hyperemic. Bleeding occurs during probing. There is moderate inflammation. There is marked redness and edema at gingiva. Ulcerations are observed. There is a predisposition to bleeding spontaneously or after probing. There is severe inflammation.
The measurements used for the evaluation of periodontal status were as follows: Pocket depth (PD) measurements The distance between base of periodontal pocket and gingival margin. Bleeding on probing (BOP) Presence of bleeding from subgingival area during probing for PD measurements. Displayed as percentage of BOP (?) sites. Gingival recession (GR) The distance between cementoenamel junction and gingival margin. Clinical attachment level (CAL) Sum of PD and GR measurements. All clinical measurements were taken from mid-buccal and mid-lingual sites and the buccal aspects of the interproximal contact area for mesial and distal sites of each tooth to the nearest 0.5 mm by using Williams periodontal probe at the baseline and third month post-treatment period. According to periodontal status at baseline, the patients were classified into 4 groups depending on the severity and
into 2 groups according to the extent of periodontal problems as follows: Severity of periodontal problems Healthy Patients having no gingival inflammation or loss of attachment. Gingivitis Patients with clinical plaque-related gingival inflammation but not loss of attachment or radiological bone loss. Mild-to-moderate periodontitis Patients with loss of attachment of 1–2 mm for the mild and 3–4 mm for the moderate periodontitis and PD [5 mm in B30 % of the sites evaluated. Severe periodontitis Patients with loss of attachment [5 mm and PD[5 mm in[30 % of the sites evaluated. Extent of periodontal problems Localized Presence of CAL and PD B30 % of the evaluated sites. Generalized Presence of attachment loss and PD [30 % of the evaluated sites. Periodontal treatment The following periodontal treatment protocol was applied to all patients. After gingival local infiltration and/or regional block anesthesia, full-mouth scaling and root planning was performed with an assortment of periodontal curettes (HuFriedy, Chicago, IL) and ultrasonic instrumentation, completed in 2 or 4 sessions depending on the extent of periodontal disease. Additionally, the patients were instructed to rinse twice daily for 1 min with a 0.12 % solution of chlorhexidine digluconate during 14 days of post-treatment period. Standard oral hygiene instructions were given, including interdental plaque control (interdental brushes) and brushing of the dorsum of the tongue twice a day. During periodontal treatment sessions, necessary tooth extractions were performed and referrals of endodontic and restorative treatments were done immediately after periodontal treatment. Biochemical parameters Hemogram biochemical parameters, intact parathormone (iPTH), peritoneal white blood cell count, HbA1c in patients with a primary diagnosis of DM, Kt/V urea (dialysis adequacy marker), and creatinine clearance. Highsensitivity C-reactive protein (hs-CRP) was measured using a BN2 model nephelometer (Dade-Behring, Germany). The expected values for hs-CRP in our laboratory ranged from 0 to 6 mg/L.
123
Int Urol Nephrol
Statistical analysis The normal distribution of the data was analyzed by Shapiro–Wilk test (Normality of data was checked by the Shapiro–Wilk test.). The normally distributed data were reported as means and SD not normally distributed ones as medians and 25th and 75th percentiles. One way ANOVA was used for the numeric variables showing normal distribution and Kruskal–Wallis test for the ones not normally distributed. Student–Newman–Keuls and Dunn’s tests were used to compare multiple pairs. Comparisons between categorical variables were done using chi-square test. Correlation between the periodontal and biochemical parameters as well as the alterations was assessed using Spearman’s rank test. To estimate the reliability of the measurements during the treatment period, 10 randomly selected patients were re-evaluated. The reliability of the continuous variables was expressed as the SD of the differences divided by two. The range of mean error for PD and attachment loss was 0.12–0.17 and 0.17–0.25, respectively. The percentage agreement for PD with 98 % of sites within 1 mm of differences in measurement and same value for attachment loss measurements was with 96 % of sites within 1 mm of differences, which indicated stable reliability during the evaluation period. Cohen k was used to describe the reliability of discrete GI and BOP values. A p value of \0.05 was considered statistically significant.
treatment values of 43 patients according to the severity of periodontal problems are presented in Table 2. Together with the significant decreases in the periodontal parameters, the decrease in hs-CRP value following periodontal treatment was also observed at a significant level. In the healthy/gingivitis group, there was no significant difference between baseline and post-treatment for any of the periodontal values. However, both the slightly-to-moderate and severe periodontitis groups showed significant improvements following periodontal treatment. The serum CRP levels both at baseline (r = 0.411, p \ 0.001) and in the post-treatment period (r = 0.431, p \ 0.001) were positively correlated with the severity of periodontal disease. The frequency of CVD and DM in relation to periodontal status is presented in Table 3. The prevalence of CVD and DM in severe periodontitis patients was 80 % in both diseases. Moreover, the prevalence of both comorbidities was significantly (p \ 0.05) higher in the severe periodontitis group than in the rest of the groups. In addition, the duration of peritoneal dialysis was assessed together with the frequency of previous peritonitis attacks in relation to periodontal status. According to our findings, there was a highly significant (p = 0.003) relation between the duration of peritoneal dialysis and severity of periodontal disease but not for the frequency of previous peritonitis attacks (Table 4).
Discussion Results Of the 68 patients included at the baseline examination, 60.3 % were men and 39.7 % were women. Mean age was 47.9 ± 12.5 years. According to the severity categories for the periodontal problems, the mean age and female/male ratios are 46 ± 12.6 and 10/12 for healthy/gingivitis, 52 ± 13.45 and 5/7 for slight-to-moderate, and 57 ± 7.27 and 1/8 for the severe group, respectively. Thirty-nine patients did not have any periodontal problem during their baseline assessment, and oral hygiene instructions alone were given to them. In addition to the oral hygiene instructions, scaling and root planning for the removal of dental plaque and calculus were performed on 51 patients at baseline. However, only 43 patients attended to the control visit performed at the third month after treatment at which the number of dropouts was 25. Table 1 shows the baseline values for both the dropout and followed patients. Except for the PD measurements (p = 0.017), there was no significant difference among all the parameters evaluated between the dropout and followed patients. The baseline and third month post-periodontal
123
Oral examination, particularly examining the periodontal tissue, is generally overlooked in uremic patients. On the other hand, it has been shown that the treatment of the cases with periodontal disease is important to improve clinical outcomes in CAPD [2]. According to our study, quality of life may be improved in CAPD patients through resolution of inflammation by diagnosis and treatment of periodontal disease. Moreover, we proposed that regular controls of the oral cavity and diagnosis of periodontal problems which might play a role in evoking systemic inflammation by means of an increase in the level of CRP can be beneficial in the management of peritoneal dialysis patients [13]. Periodontal disease is prevalent, severe, and under recognized in CKD. It is particularly advanced in patients maintained on HD comparable to the full symptomatic form of periodontitis, which is less severe in CAPD and pre-dialysis subjects, and more developed in all groups of renal failure patients than in the general population [15]. Prophylaxis and early dental care should be intensified in CKD patients; this may, hopefully, have a beneficial impact on their general health status.
Int Urol Nephrol Table 1 Comparison between the dropout and follow-up patients in terms of biochemical and periodontal parameters
Variables
All patients n = 68
Dropout patients n = 25
Follow-up patients n = 43
27/41
11/14
16/27
Gender Female/male
p 0.383
Severity of periodontal problems
0.237
Healthy/gingivitis
39
17
Slightly moderate
19
7
22 12
Severe
10
1
9
Age (years)
47.9 ± 12.5
44.7 ± 12.7
49.8 ± 12.1
0.101
WBC (mm3/l)
7.4 ± 2.4
7.5 ± 2.4
7.4 ± 2.6
0.807
Hemoglobin (g/dL)
11.4 ± 1.9
11.1 ± 1.8
11.6 ± 2.1
0.284
Glucose (mg/dL)
97 (57–407)
98 (75–387)
97 (57–407)
0.651
Triglyceride (mg/v) Cholesterol (mg/dL)
151 (46–508) 189.3 ± 49.2
112 (46–559) 193.5 ± 64.1
160 (48–508) 187.7 ± 39.2
0.156 0.633
LDL (mg/dL)
113.1 ± 41.7
117.1 ± 49.2
110.6 ± 37.5
0.525
BUN (mg/dL)
54.1 ± 16.3
56.2 ± 13.3
52.8 ± 17.9
0.420
Creatinine (mg/dL)
8.3 ± 3.4
8.8 ± 3.1
8.1 ± 3.5
0.415
Calcium (mg/dL)
8.6 ± 1.1
8.5 ± 1.6
8.7 ± 0.8
0.661
Phosphorus (mg/dL)
4.4 ± 1.1
4.6 ± 0.9
4.3 ± 1.1
0.123
Albumin (g/dL)
3.0 ± 1.0
2.8 ± 1.1
3.1 ± 0.9
0.079
PTH (pq/dL)
286 (5–1,467)
293 (10–1,467)
273 (5.1–1,419)
0.940
Kt/V
2.1 (1.2–3.9)
2.0 (1.5–3.4)
2.2(1.2–3.9)
0.716
CRP (mg/dL)
9.7 (3.1–49.3)
5.7 (3.1–36.2)
10.2 (3.2–49.3)
0.210
HbA1C (%)
7.7 ± 1.4
7.2 ± 1.4
8.3 ± 1.5
0.287
Plaque index
2.7 (0.8–3)
2.4 (0.8–3)
3 (1–3)
0.170
Gingival index
1.8 (0.7–2.4)
1.6 (0.7–2)
2 (0.9–2.4)
0.556
Pocket depth
2.49 ± 0.87
2.25 ± 0.63
2.77 ± 1.13
0.017
Bleeding on probing
63.9 ± 3.1
66.9 ± 3.07
61.5 ± 3.1
0.487
Clinical attachment loss Gingival recession
1.6 ± 1.54 0.28 ± 0.92
1.1 ± 1.94 0.21 ± 0.92
2.01 ± 1.44 0.32 ± 0.91
0.095 0.636
In view of the causative association among periodontal infection, generalized inflammation, and important systemic diseases, it is not unreasonable to hypothesize that, which should be initiated in the very early stage of CKD, may have a positive effect on patients’ morbidity and survival. Related to the effect of periodontal treatment in CKD patients, an impressive threefold decrease in CRP in HD patients was reported to occur just after 4–6 weeks traditional periodontal therapy [16]. The comparison of data between baseline and third month post-periodontal treatment demonstrated a decline in clinical periodontal status and the improvement of CRP level as an inflammatory marker in our study. Significant positive correlations between CRP and periodontal status as well as for the alterations were also reported by Siribamrungwong et al. [17] who evaluated systemic responses following subsequent non-surgical and surgical periodontal treatments lasting more than 6 months in CAPD patients. Although the prevalence and severity of periodontitis were comparable in both studies, the length of evaluation was longer in
their study than in ours. However, the results of both studies showed successful periodontal treatment could have been achieved in PD with subsequent significant improvement in CRP levels. The presence of oral biofilm infection is not only related with local inflammatory reaction causing destruction of tooth supporting tissues but also provokes systemic inflammation [18]. In chronic renal disease, which affects the whole body, it is known that the periodontal tissues are adversely affected over time and that periodontitis is more frequent in CKD patients compared to healthy subjects [19]. Neglecting oral care due to the primary disease, disrupted metabolism of the periodontal tissues due to uremic toxins, and structural impairment of alveolar bone due to renal osteodystrophy could be the cofactors for the higher prevalence of periodontal disease in CKD patients [2–4]. In addition, this group of patients becomes more vulnerable to infections as a consequence of immunosuppression and malnutrition. Thus, local infections with systemic effects such as periodontitis can occur more frequently and readily [20].
123
Int Urol Nephrol Table 2 Comparison of parameters of demographic, biochemical, and periodontal among three groups according to severity of periodontal disease Parameters
White blood cell count (mm3) Hemoglobin (g/dL) Fasting glucose (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Serum calcium (mg/dL) Serum phosphorus (mg/dL) Serum albumin (g/dL) Transferrin saturation (%) hs-CRP(mg/L) Intact parathormon (pg/mL) Kt/vurea Plaque index Gingival index Pocket depth Bleeding on probing (%) Clinical attachment loss Gingival recession
Pre-treatment parameters
Post-treatment parameters
Healthy/ gingivitis (n = 22)
Slightly to moderate (n = 12)
Severe (n = 9)
6,716 ± 2,047a
9,007 ± 3,499
6,898 ± 1,107
11.8 ± 2.0
11.1 ± 2.2
93 (73–407)
Healthy/ gingivitis (n = 22)
Slightly to moderate (n = 12)
Severe (n = 9)
p value*
0.032
7,447 ± 1,937
8,820 ± 1,865
8,337 ± 1,849
0.137
12.2 ± 2.0
0.435
11.8 ± 1.6
12.5 ± 1.2
12.4 ± 1.6
0.374
114 (67–377)
102 (57–236)
0.352
93 (73–578)
86 (72–250)
86 (80–158)
0.802
187 ± 45
187 ± 35
188 ± 33
0.999
193 ± 75
188 ± 31
188 ± 32
0.968
150 (63–908)
162 (71–283)
243 (48–473)
0.260
155 (71–650)
164 (63–294)
285 (132–368)
0.199
109 ± 42
116 ± 34
109 ± 30
0.843
108 ± 57
112 ± 34
99 ± 35
0.827
38.7 ± 12.8
40.1 ± 13.4
32.0 ± 3.7
0.262
39 ± 13
41 ± 14
37 ± 9
0.829
8.7 ± 0.9
8.7 ± 0.7
8.7 ± 1.0
0.967
8.7 ± 0.8
8.9 ± 1.0
9.0 ± 1.2
0.728
4.2 ± 1.1
3.8 ± 1.0
4.0 ± 1.3
0.588
4.5 ± 2.1
4.3 ± 0.8
4.9 ± 1.4
0.770
3.1 ± 0.4
2.9 ± 0.4
3.2 ± 0.3
0.321
3.2 ± 0.6
3.2 ± 0.4
3.3 ± 0.3
0.758
28 ± 11
33 ± 15
30 ± 5
0.540
34 ± 14
31 ± 16
30 ± 6
0.690
5.6 (3.2–36.2)b 249 (25–1,067)
11.2 (3.2–38.3)** 248 (5–976)
26.2 (3.2–49.3)*** 387 (151–1,419)
0.01 0.379
4.0 (3.2–23.2) 225 (113–905)
5.6 (3.2–45.1) 382 (4–1,409)
15.3 (10.1–36.6) 195 (127–1,409)
0.012 0.914
2.3 2.5 1.4 2.1 0.5
2.5 3.0 2.0 2.7 0.7
1.8 3.0 2.0 4.4 0.8
2.1 2.4 1.3 2.5 0.4
(1.7–2.7) ± 0.4** ± 0.6 (1.2–5.6) (0–1.0)
0.380 0.134 0.290 0.082 0.364
(1.5–5.9) (1.0–3.0) (1.0–2.0)b (1.1–2.9)b (0.1–1.0)
(1.5–3.7) (1.0–3.0) (1.0–2.5) (1.6–4.0) (0.3–1.0)
p value*
(1.3–4.9) (2.1–3.0) (1.3–2.0) (2.6–5.8) (0–1.0)
0.292 0.122 0.003 \0.001 0.300
2.5 (1.3–5.9) 1.8 (1.0–2.7) ± 0.4 1.9 (1.1–3.2) 0.4 (0–1.0)
2.2 2.2 1.4 2.0 0.5
0.2 (0–1.1)
2.3 (1.2–3.8)**
3.8 (1.2–8.8)***
0.01
0 (-0.8–1.9)
0.3 (-0.7–1.6)
0.5 (0–4.6)
0.004
0 (0–0)b
3.2 (1.5–4.0)
5.9 (4.1–9.8)
\0.001
0 (0–0)b
0.1 (0–1.6)
0 (–0.4–4.3)
0.007
(1.8–4.9) ± 0.9** ± 0.5 (1.2–3.3) (0.1–1.0)
LDL low-density lipoprotein, HDL high-density lipoprotein, hs-CRP high-sensitivity C-reactive protein * Difference among the study groups ** Significant difference between pre- and post-treatment periods for slightly/moderate periodontitis group (p = 0.014) *** Significant difference between pre- and post-treatment periods for severe periodontitis group (p = 0.001) a Significant difference between healthy/gingivitis and slightly moderate periodontitis groups (p = 0.031) b Significant difference between healthy/gingivitis and slightly moderate (p = 0.023) and severe periodontitis groups (p \ 0.001)
It is known that periodontitis causes arteriosclerosis and related complications via low-level systemic inflammation and these adversely affect the survival rate of patients with
123
chronic renal failure undergoing peritoneal dialysis and hemodialysis. In fact, systemic inflammation and arteriosclerotic complications are decreased by effective
Int Urol Nephrol Table 3 Relationship between severity of periodontal disease and presence of cardiovascular disease (CVD)/diabetes mellitus (DM) Healthy and gingivitis n (%)
Slightly to moderate n (%)
Severe
p
n (%)
CVD Positive
14 (35.5)
9 (47.4)
8 (80.0)
Negative
25 (64.5)
10 (52.6)
2 (20.0)
Total
39 (100)
19 (100)
10 (100)
Positive
10 (25.5)
10 (52.6)
8 (80)
Negative
29 (74.5)
9 (47.4)
Total
39 (100)
19 (100)
0.028
DM 0.004
2 (20) 10 (100)
Table 4 Relationship between duration of peritoneal dialysis and number of peritonitis attacks in all patients median (25th and 75th percentiles) Groups
Duration (month) of peritoneal dialysis
Number of peritonitis attacks
Healthy and gingivitis (n = 39)
24 (12–64)
1 (0–5)
Slightly to moderate (n = 19)
48 (36–60)
2 (0–7)
Severe (n = 10)
56 (36–70)
2 (0–2)
p
0.003
0.235
periodontal therapy [21, 22], and several studies [9] suggest that not only can periodontitis increase inflammatory markers for CVD, such as CRP, but effective periodontal therapy can decrease CRP values. Hs-CRP is an extremely sensitive and non-specific acute phase marker for inflammation that is produced in response to many forms of tissue injury [23]. Although periodontitis is generally chronic in nature, acute phase elements, such as hs-CRP, are also part of the innate immunity response which has been determined in periodontitis [24, 25]. There is strong evidence from cross-sectional studies that plasma hs-CRP in periodontitis is increased compared with controls. There is modest evidence on the effect of periodontal therapy in lowering the levels of CRP [8]. Thus, it was plausible to establish a link between periodontitis and systemic inflammation. In this study, we found that the rate of periodontal disease was markedly higher and that hs-CRP values increased in parallel to severity of periodontitis in patients undergoing CAPD. After periodontal treatment, a significant decrease in hs-CRP level was observed in the control visit. Therefore, physicians should consider intraoral infections such as periodontitis if there was no known infectious focus such as otitis, peritonitis, cellulitis, or urinary tract infection in case of unexplained hs-CRP increase.
Several oral changes occur in patients with DM [26]. Although it is difficult to reach definitive conclusions regarding the specific effects of diabetes on the periodontium, severe gingival inflammation, deep periodontal pocket, rapid bone loss, and periodontal abscess occur more frequently in diabetic patients with poor oral hygiene [27, 28]. In recent studies, it has been suggested that there is an increased susceptibility to severe infections including periodontitis in patients with poorly controlled DM [29, 30]. It was reported that periodontal disease is relevant to complications of DM including neuropathy, nephropathy, retinopathy, and micro/macrovascular diseases [31, 32]. Finally, a bidirectional relationship between DM and periodontitis has been suggested by Iacopino [33]. More recently, higher serum hs-CRP levels and chronic periodontitis have been demonstrated in patients with cardiovascular disease [24, 25]. Indeed, the relation between CVD and CKD is well known [34]. The increasing prevalence of periodontal disease in peritoneal dialysis patients prompted us to investigate the temporal relation with inflammation to severity of periodontitis and the presence of CVD. Thus, it seems that periodontitis might be correlated with the presence of CVD in the CAPD population. According to our findings, there was a highly significant relation between the duration of peritoneal dialysis and severity of periodontal disease but not for the frequency of previous peritonitis attacks. Our findings are in agreement with the study published by Sekiguchi et al. [35] where the mean values for PD and CAL were statistically significantly higher in groups with longer (more than 3 years) duration compared to the group of\3 years. These data are also in agreement with the reports from Duran et al. [36] and Cengiz et al. [17] (who found a positive correlation between the length of time their subjects had been on HD and decrease in oral health status). The potential limitations of our study include limited sample size, presence of almost 40 % of dropouts, and higher prevalence of health/gingivitis within the follow-up group. Thus, there is need for further validation in a larger population with a control group. Also, there was a lack of usage of detailed inflammation markers and conventional methods to show the presence of CVD. The literature supports a bidirectional relation between CKD and periodontal disease. Patients with CKD have higher prevalence of periodontal disease while non-surgical periodontal therapy has been shown to decrease the systemic inflammatory burden in patients with CKD, especially in those undergoing dialysis therapy. Most of the trials conducted have observed the effect of periodontal therapy on hs-CRP levels. In conclusion, we aimed to re-assess periodontitis after diagnosis and management in a group of patients undergoing CAPD. We think that early recognition and treatment
123
Int Urol Nephrol
of periodontitis may contribute to improving the clinical course of CAPD and may target the reason for unexplained increased CRP level as a sign of systemic inflammation in patients undergoing peritoneal dialysis. Conflict of interest
None.
18.
19.
20.
References 1. Parkar SM, Ajithkrishnan CG (2012) Periodontal status in patients undergoing hemodialysis. Indian J Nephrol 22:246–250 2. Akar H, Akar GC, Carrero JJ et al (2011) Systemic consequences of poor oral health in chronic kidney disease patients. Clin J Am Soc Nephrol 6:218–226 3. Bayraktar G, Kurtulus I, Kazancioglu R et al (2009) Oral health and inflammation in patients with end-stage renal failure. Perit Dial Int 29:472–479 4. Nadeem M, Stephen L, Schubert C et al (2009) Association between periodontitis and systemic inflammation in patients with end-stage renal disease. SADJ 64:470–473 5. Siribamrungwong M, Puangpanngam K (2012) Treatment of periodontal diseases reduces chronic systemic inflammation in maintenance hemodialysis patients. Ren Fail 34:171–175 6. Proctor R, Kumar N, Stein A et al (2005) Oral and dental aspects of chronic renal failure. J Dent Res 84:199–208 7. Cengiz MI, Bal S, Go¨kc¸ay S et al (2007) Does periodontal disease reflect atherosclerosis in continuous ambulatory peritoneal dialysis patients? J Periodontol 78:1926–1934 8. Paraskevas S, Huizinga JD, Loos BG (2008) A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol 35:277–290 9. Craig RG, Kotanko P, Kamer AR et al (2007) Periodontal diseases—a modifiable source of systemic inflammation for the endstage renal disease patient on haemodialysis therapy? Nephrol Dial Transplant 22:312–315 10. Brito F, Almeida S, Figueredo CM et al (2012) Extent and severity of chronic periodontitis in chronic kidney disease patients. J Periodontal Res 47:426–430 11. Ismail G, Dumitriu HT, Dumitriu AS (2013) Periodontal disease: a covert source of inflammation in chronic kidney disease patients. Int J Nephrol 2013:515796 12. Chambrone L, Foz AM, Guglielmetti MR et al (2013) Periodontitis and chronic kidney disease: a systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate. J Clin Periodontol 40:443–456 13. Fisher MA, Borgnakke WS, Taylor GW (2010) Periodontal disease as a risk marker in coronary heart disease and chronic kidney disease. Curr Opin Nephrol Hypertens 19:519–526 14. Lo¨e H (1967) The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol 38:610–616 15. Borawski J, Wilczyn´ska-Borawska M, Stokowska W et al (2007) The periodontal status of pre-dialysis chronic kidney disease and maintenance dialysis patients. Nephrol Dial Transplant 22:457–464 16. Kadiroglu AK, Kadiroglu ET, Sit D et al (2006) Periodontitis is an important and occult source of inflammation in hemodialysis patients. Blood Purif 24:400–404 17. Siribamrungwong M, Yothasamutr K, Puangpanngam K (2013) Periodontal treatment reduces chronic systemic inflammation in
123
21.
22.
23. 24.
25.
26.
27.
28. 29.
30.
31.
32.
33. 34.
35.
36.
peritoneal dialysis patients. Ther Apher Dial. doi:10.1111/17449987.12105 Grossi SG, Mealey BL, Rose LF (2004) Effect of periodontal infection on systemic health and well-being. In: Rose LF, Mealey BL, Genco RJ, Cohen DW (eds) Periodontics: medicine, surgery, and implants. Elsevier, Amsterdam, pp 846–859 Cengiz MI, Su¨mer P, Cengiz S et al (2009) The effect of the duration of the dialysis in hemodialysis patients on dental and periodontal findings. Oral Dis 15:336–341 El-Shinnawi U, Soory M (2013) Associations between periodontitis and systemic inflammatory diseases: response to treatment. Recent Pat Endocr Metab Immune Drug Discov 7:169–188 Paparello J, Kshirsagar A, Batlle D et al (2002) Comorbidity and cardiovascular risk factors in patients with chronic kidney disease. Semin Nephrol 22:494–506 Yeun JY, Levine RA, Mantadilok V et al (2000) C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis populations. Am J Kidney Dis 35:469–476 Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111:1805–1812 Persson GR, Ohlsson O, Pettersson T et al (2003) Chronic periodontitis, a significant relationship with acute myocardial infarction. Eur Heart J 24:2108–2115 Persson GR, Pettersson T, Ohlsson O et al (2005) High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis. J Clin Periodontol 32:219–224 Bascones-Martinez A, Matesanz-Perez P, Escribano-Bermejo M et al (2011) Periodontal disease and diabetes—review of the literature. Med Oral Patol Oral Cir Bucal 16:722–729 Newman MG, Takei HH, Carranza FA (2002) Influence of systemic disease and disorders on the periodontium. In: Klokkevold PR, Mealey BL, Carranza FA (eds) Carranza’s clinical periodontology, 9th edn. WB Saunders, Philadelphia, pp 208–209 Negrato CA, Tarzia O, Jovanovicˇ L et al (2013) Periodontal disease and DM. J Appl Oral Sci 21:1–12 Sastrowijoto S, van der Velden U, van Steenbergen T et al (1990) Improved metabolic control, clinical periodontal status, and subgingival microbiology in insulin-dependent DM. J Clin Periodontol 17:233–242 Karjalainen K, Knuuttila M (1996) The onset of diabetes and poor metabolic control increases gingival bleeding in children and adolescents with insulin-dependent DM. J Clin Periodontol 23:1060–1067 Taylor GW (2001) Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective. Ann Periodontol 6:99–112 Southerland JH, Taylor GW, Moss K et al (2000) Commonality in chronic inflammatory diseases: periodontitis, diabetes, and coronary artery disease. Periodontology 40:130–143 Iacopino AM (2001) Periodontitis and diabetes inter-relationships: role of inflammation. Ann Periodontol 6:125–137 Shoji T, Emoto M, Shinohara K et al (2001) Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease. J Am Soc Nephrol 12:2117–2124 Sekiguchi RT, Pannuti CM, Silva HT Jr et al (2012) Decrease in oral health may be associated with length of time since beginning dialysis. Spec Care Dentist 32:6–10 Duran I, Erdemir EO (2004) Periodontal treatment needs of patients with renal disease receiving haemodialysis. Int Dent J 54:274–278
NEPHROLOGY - ORIGINAL PAPER
An ignored cause of inflammation in patients undergoing continuous ambulatory peritoneal dialysis: periodontal problems Ismail Kocyigit • Hasan Esat Yucel • Omer Cakmak • Fatma Dogruel • Du¨rdane Banu Durukan • Hafsa Korkar • Aydin Unal • Murat Hayri Sipahioglu Oktay Oymak • Cem A. Gurgan • Bulent Tokgoz
•
Received: 28 January 2014 / Accepted: 8 April 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract Aim We aimed to assess whether there is a significant relation between periodontal health status and inflammation in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and also to reveal the efficiency of periodontal treatment in patients with various degrees of periodontal problems. Patients and methods Overall, 68 patients undergoing CAPD were included in the study. Clinical indices and measurements were obtained at baseline and panoramic radiographies were used for the diagnosis. According to the baseline values, patients were stratified into four groups according to the severity of periodontal problems as follows: healthy/gingivitis, slight-to-moderate, and severe periodontitis. A control examination was performed 3 months after the periodontal treatment for only 43 patients. Clinical and laboratory parameters before and after treatment were compared.
I. Kocyigit (&) A. Unal M. H. Sipahioglu O. Oymak B. Tokgoz Department of Nephrology, Erciyes University Medical Faculty, 38039 Kayseri, Turkey e-mail: [email protected] H. E. Yucel H. Korkar Department of Internal Medicine, Erciyes University Medical Faculty, Kayseri, Turkey O. Cakmak D. B. Durukan C. A. Gurgan Department of Periodontology, Erciyes University Faculty of Dentistry, Kayseri, Turkey F. Dogruel Department of Internal Medicine, Erciyes University Faculty of Dentistry, Kayseri, Turkey
Results The frequency of periodontal disease was found to be high in uremic patients on CAPD. The frequency and severity of periodontitis was also found to be significantly (p \ 0.01) higher in patients with high sensitive C-reactive protein levels and longer duration of peritoneal dialysis (p \ 0.01). In addition, the periodontitis rate was found to be higher in patients with cardiovascular disease (p \ 0.05) and diabetes mellitus (p \ 0.01). Conclusion A meticulous periodontal examination should be a routine part of management of the uremic patients on CAPD because periodontal disease could be one of the hidden sources of unexplained inflammatory status. Keywords Continuous ambulatory peritoneal dialysis Periodontal disease Inflammation
Introduction One of the most important goals in patients with chronic renal disease is to improve their quality of life [1]. Periodontal disease or periodontitis is an inflammatory disease of the gingiva and tissues surrounding teeth due to infectious reasons, which may lead to progressive loss of the supportive tissues of the teeth and consequently to alveolar bone loss. The severity of the disease is determined by the inflammatory response of the body [2, 3]. In addition, periodontitis is associated with disorders that pointed out systemic inflammation. The most remarkable example of this is the relationship between periodontal disease and cardiovascular diseases (CVD) such as atherosclerosis, myocardial infarction, and stroke [4, 5]. Oral hygiene and frequency of periodontal disease have become important issues in chronic renal disease patients. Thus, early assessment of oral health is important to decrease the risk of potential oral cavity infections [6].
123
Int Urol Nephrol
Periodontal health was found to be poor in continuous ambulatory peritoneal dialysis (CAPD) patients, and this inflammatory status was related with markers of malnutrition, inflammation, and atherosclerosis [7]. The prevalence of atherosclerotic complications (myocardial infarction, stroke, and sudden death) is increased in end-stage renal disease (ESRD) patients, especially in hemodialysis patients. Increasing evidence suggests that both in the general population and in dialysis patients, systemic inflammation plays an important role in the pathogenesis of atherosclerotic complications. In the general population, also, evidence shows that moderate to severe periodontitis can contribute to inflammatory burden by increasing highly sensitive C-reactive protein (hs-CRP) levels [8], the most important acute phase protein, which is monitored as a systemic marker of inflammation and also of endothelial dysfunction it is also used as an initial predictor of atherosclerotic events, and may contribute to the increase in the prevalence of atherosclerotic events. Moreover, the results of interventional studies reveal that effective phase I (non-surgical treatment) periodontal therapy may decrease serum hs-CRP levels [8, 9]. Considering that moderate to severe periodontal diseases have a higher prevalence in chronic kidney disease (CKD) and in dialysis populations [3, 10, 11], chronic and generalized periodontitis might be an ignored source of systemic inflammation in ESRD patients and may add to the chronic inflammatory status in CKD. According to very recently published systematic reviews, there is quite consistent evidence to support the positive association between periodontitis and CKD, as well as the positive effect of periodontal treatment on the estimated glomerular filtration rate [12]. There is a presence of strong evidence linking periodontitis with CVD in addition to CKD where improving patients’ oral health could possibly reduce CVD and CKD risks [13]. The main aim of our study was to evaluate the severity and extent of periodontal disease in patients undergoing CAPD. A secondary aim was to detect the changes in inflammatory status by providing appropriate treatment in cases with periodontal disease and finally to determine the association with other comorbidities such as diabetes mellitus (DM) and CVD.
Materials and methods This study was conducted in patients undergoing CAPD managed in the outpatient clinic for peritoneal dialysis at the Erciyes University School of Medicine between August 2012 and April 2013. The dental and periodontal examinations were performed by a periodontologist in the Department of Periodontology of the Faculty of Dentistry at Erciyes University.
123
Inclusion criteria were as follows: 1. 2. 3.
Presence of C15 natural teeth. Year of age C18. Undergoing peritoneal dialysis. Exclusion criteria were as follows:
1.
2. 3.
History of antibiotic therapy within the previous 6 months (including peritonitis treatment) and antiinflammatory drugs within the previous 3 months. Pregnancy or use of contraceptives or any other hormone therapy. Periodontal treatment within the previous 12 months.
Patients were informed about the tests and test methodology that would be used and about potential adverse effects. All patients gave their written consent for the test and physical examination. Also, all volunteer patients were informed about the aim and methods of this study and gave their written consent to participate. This study was conducted in full accordance with the applicable ethical principles, including the World Medical Association Declaration of Helsinki, and was independently reviewed and approved by the Ethical Committee in the Faculty of Medicine. In our center, 175 patients, of whom 155 (89 %) are treated with PD, are currently being followed. Among those treated with PD, 72 who were found to be suitable according to the inclusion/exclusion criteria were referred to the Faculty of Dentistry for diagnosis and treatment. Overall, 68 volunteer patients were included in the study and control visits were performed 3 months after the periodontal treatment. Enrolled patients were evaluated in terms of systemic inflammation and peritonitis both at baseline and at the control visit. None of the patients had any signs of systemic infection. The evaluated signs and symptoms of systemic infection were abdominal, nape, back and forehead pain, fever, nausea, vomiting, diarrhea, dysuria, cough, or rash. In addition to these symptoms, pain, fever, pus, redness, and swelling at the affected area were evaluated as the symptoms of local infection. A history of plaque based on coronary angiography, percutaneous transluminal coronary angioplasty (PTCA), or coronary bypass was accepted as CVD. In all the patients included, the following parameters were evaluated: periodontal clinical measurements and indices, and panoramic X-ray examinations. Periodontal parameters The following clinical parameters were evaluated both at the baseline and third month following the periodontal treatment:
Int Urol Nephrol
The indices used for the evaluation of oral health status were as follows: Plaque index (PI) [14]; presence of bacterial plaque on tooth/root surface. Plaque index scoring was as follows: 1. 2.
3.
4.
No plaque at gingival area in tooth. Presence of plaque which is not macroscopically visible at free gingival margin and tooth surface adjacent to gingival margin but appears as a film at the tip of probe, when probe is moved through orifice of gingival sulcus. Gingival area and tooth surface adjacent to gingival margin are coated by plaque with mild to moderate thickness and plaque is macroscopically visible. Presence of intense soft tissue attachment or plaque at gingival pocket and tooth surface adjacent to gingival edge.
Gingival index (GI) [14]; presence of bleeding at the marginal gingiva. Scoring was as follows: 1. 2.
3.
4.
There is no inflammation sign in marginal gingival. Gingiva is healthy. There is mild discoloration and edema at gingiva. No bleeding occurs during probing. There is mild inflammation. Gingiva is bright, edematous, and hyperemic. Bleeding occurs during probing. There is moderate inflammation. There is marked redness and edema at gingiva. Ulcerations are observed. There is a predisposition to bleeding spontaneously or after probing. There is severe inflammation.
The measurements used for the evaluation of periodontal status were as follows: Pocket depth (PD) measurements The distance between base of periodontal pocket and gingival margin. Bleeding on probing (BOP) Presence of bleeding from subgingival area during probing for PD measurements. Displayed as percentage of BOP (?) sites. Gingival recession (GR) The distance between cementoenamel junction and gingival margin. Clinical attachment level (CAL) Sum of PD and GR measurements. All clinical measurements were taken from mid-buccal and mid-lingual sites and the buccal aspects of the interproximal contact area for mesial and distal sites of each tooth to the nearest 0.5 mm by using Williams periodontal probe at the baseline and third month post-treatment period. According to periodontal status at baseline, the patients were classified into 4 groups depending on the severity and
into 2 groups according to the extent of periodontal problems as follows: Severity of periodontal problems Healthy Patients having no gingival inflammation or loss of attachment. Gingivitis Patients with clinical plaque-related gingival inflammation but not loss of attachment or radiological bone loss. Mild-to-moderate periodontitis Patients with loss of attachment of 1–2 mm for the mild and 3–4 mm for the moderate periodontitis and PD [5 mm in B30 % of the sites evaluated. Severe periodontitis Patients with loss of attachment [5 mm and PD[5 mm in[30 % of the sites evaluated. Extent of periodontal problems Localized Presence of CAL and PD B30 % of the evaluated sites. Generalized Presence of attachment loss and PD [30 % of the evaluated sites. Periodontal treatment The following periodontal treatment protocol was applied to all patients. After gingival local infiltration and/or regional block anesthesia, full-mouth scaling and root planning was performed with an assortment of periodontal curettes (HuFriedy, Chicago, IL) and ultrasonic instrumentation, completed in 2 or 4 sessions depending on the extent of periodontal disease. Additionally, the patients were instructed to rinse twice daily for 1 min with a 0.12 % solution of chlorhexidine digluconate during 14 days of post-treatment period. Standard oral hygiene instructions were given, including interdental plaque control (interdental brushes) and brushing of the dorsum of the tongue twice a day. During periodontal treatment sessions, necessary tooth extractions were performed and referrals of endodontic and restorative treatments were done immediately after periodontal treatment. Biochemical parameters Hemogram biochemical parameters, intact parathormone (iPTH), peritoneal white blood cell count, HbA1c in patients with a primary diagnosis of DM, Kt/V urea (dialysis adequacy marker), and creatinine clearance. Highsensitivity C-reactive protein (hs-CRP) was measured using a BN2 model nephelometer (Dade-Behring, Germany). The expected values for hs-CRP in our laboratory ranged from 0 to 6 mg/L.
123
Int Urol Nephrol
Statistical analysis The normal distribution of the data was analyzed by Shapiro–Wilk test (Normality of data was checked by the Shapiro–Wilk test.). The normally distributed data were reported as means and SD not normally distributed ones as medians and 25th and 75th percentiles. One way ANOVA was used for the numeric variables showing normal distribution and Kruskal–Wallis test for the ones not normally distributed. Student–Newman–Keuls and Dunn’s tests were used to compare multiple pairs. Comparisons between categorical variables were done using chi-square test. Correlation between the periodontal and biochemical parameters as well as the alterations was assessed using Spearman’s rank test. To estimate the reliability of the measurements during the treatment period, 10 randomly selected patients were re-evaluated. The reliability of the continuous variables was expressed as the SD of the differences divided by two. The range of mean error for PD and attachment loss was 0.12–0.17 and 0.17–0.25, respectively. The percentage agreement for PD with 98 % of sites within 1 mm of differences in measurement and same value for attachment loss measurements was with 96 % of sites within 1 mm of differences, which indicated stable reliability during the evaluation period. Cohen k was used to describe the reliability of discrete GI and BOP values. A p value of \0.05 was considered statistically significant.
treatment values of 43 patients according to the severity of periodontal problems are presented in Table 2. Together with the significant decreases in the periodontal parameters, the decrease in hs-CRP value following periodontal treatment was also observed at a significant level. In the healthy/gingivitis group, there was no significant difference between baseline and post-treatment for any of the periodontal values. However, both the slightly-to-moderate and severe periodontitis groups showed significant improvements following periodontal treatment. The serum CRP levels both at baseline (r = 0.411, p \ 0.001) and in the post-treatment period (r = 0.431, p \ 0.001) were positively correlated with the severity of periodontal disease. The frequency of CVD and DM in relation to periodontal status is presented in Table 3. The prevalence of CVD and DM in severe periodontitis patients was 80 % in both diseases. Moreover, the prevalence of both comorbidities was significantly (p \ 0.05) higher in the severe periodontitis group than in the rest of the groups. In addition, the duration of peritoneal dialysis was assessed together with the frequency of previous peritonitis attacks in relation to periodontal status. According to our findings, there was a highly significant (p = 0.003) relation between the duration of peritoneal dialysis and severity of periodontal disease but not for the frequency of previous peritonitis attacks (Table 4).
Discussion Results Of the 68 patients included at the baseline examination, 60.3 % were men and 39.7 % were women. Mean age was 47.9 ± 12.5 years. According to the severity categories for the periodontal problems, the mean age and female/male ratios are 46 ± 12.6 and 10/12 for healthy/gingivitis, 52 ± 13.45 and 5/7 for slight-to-moderate, and 57 ± 7.27 and 1/8 for the severe group, respectively. Thirty-nine patients did not have any periodontal problem during their baseline assessment, and oral hygiene instructions alone were given to them. In addition to the oral hygiene instructions, scaling and root planning for the removal of dental plaque and calculus were performed on 51 patients at baseline. However, only 43 patients attended to the control visit performed at the third month after treatment at which the number of dropouts was 25. Table 1 shows the baseline values for both the dropout and followed patients. Except for the PD measurements (p = 0.017), there was no significant difference among all the parameters evaluated between the dropout and followed patients. The baseline and third month post-periodontal
123
Oral examination, particularly examining the periodontal tissue, is generally overlooked in uremic patients. On the other hand, it has been shown that the treatment of the cases with periodontal disease is important to improve clinical outcomes in CAPD [2]. According to our study, quality of life may be improved in CAPD patients through resolution of inflammation by diagnosis and treatment of periodontal disease. Moreover, we proposed that regular controls of the oral cavity and diagnosis of periodontal problems which might play a role in evoking systemic inflammation by means of an increase in the level of CRP can be beneficial in the management of peritoneal dialysis patients [13]. Periodontal disease is prevalent, severe, and under recognized in CKD. It is particularly advanced in patients maintained on HD comparable to the full symptomatic form of periodontitis, which is less severe in CAPD and pre-dialysis subjects, and more developed in all groups of renal failure patients than in the general population [15]. Prophylaxis and early dental care should be intensified in CKD patients; this may, hopefully, have a beneficial impact on their general health status.
Int Urol Nephrol Table 1 Comparison between the dropout and follow-up patients in terms of biochemical and periodontal parameters
Variables
All patients n = 68
Dropout patients n = 25
Follow-up patients n = 43
27/41
11/14
16/27
Gender Female/male
p 0.383
Severity of periodontal problems
0.237
Healthy/gingivitis
39
17
Slightly moderate
19
7
22 12
Severe
10
1
9
Age (years)
47.9 ± 12.5
44.7 ± 12.7
49.8 ± 12.1
0.101
WBC (mm3/l)
7.4 ± 2.4
7.5 ± 2.4
7.4 ± 2.6
0.807
Hemoglobin (g/dL)
11.4 ± 1.9
11.1 ± 1.8
11.6 ± 2.1
0.284
Glucose (mg/dL)
97 (57–407)
98 (75–387)
97 (57–407)
0.651
Triglyceride (mg/v) Cholesterol (mg/dL)
151 (46–508) 189.3 ± 49.2
112 (46–559) 193.5 ± 64.1
160 (48–508) 187.7 ± 39.2
0.156 0.633
LDL (mg/dL)
113.1 ± 41.7
117.1 ± 49.2
110.6 ± 37.5
0.525
BUN (mg/dL)
54.1 ± 16.3
56.2 ± 13.3
52.8 ± 17.9
0.420
Creatinine (mg/dL)
8.3 ± 3.4
8.8 ± 3.1
8.1 ± 3.5
0.415
Calcium (mg/dL)
8.6 ± 1.1
8.5 ± 1.6
8.7 ± 0.8
0.661
Phosphorus (mg/dL)
4.4 ± 1.1
4.6 ± 0.9
4.3 ± 1.1
0.123
Albumin (g/dL)
3.0 ± 1.0
2.8 ± 1.1
3.1 ± 0.9
0.079
PTH (pq/dL)
286 (5–1,467)
293 (10–1,467)
273 (5.1–1,419)
0.940
Kt/V
2.1 (1.2–3.9)
2.0 (1.5–3.4)
2.2(1.2–3.9)
0.716
CRP (mg/dL)
9.7 (3.1–49.3)
5.7 (3.1–36.2)
10.2 (3.2–49.3)
0.210
HbA1C (%)
7.7 ± 1.4
7.2 ± 1.4
8.3 ± 1.5
0.287
Plaque index
2.7 (0.8–3)
2.4 (0.8–3)
3 (1–3)
0.170
Gingival index
1.8 (0.7–2.4)
1.6 (0.7–2)
2 (0.9–2.4)
0.556
Pocket depth
2.49 ± 0.87
2.25 ± 0.63
2.77 ± 1.13
0.017
Bleeding on probing
63.9 ± 3.1
66.9 ± 3.07
61.5 ± 3.1
0.487
Clinical attachment loss Gingival recession
1.6 ± 1.54 0.28 ± 0.92
1.1 ± 1.94 0.21 ± 0.92
2.01 ± 1.44 0.32 ± 0.91
0.095 0.636
In view of the causative association among periodontal infection, generalized inflammation, and important systemic diseases, it is not unreasonable to hypothesize that, which should be initiated in the very early stage of CKD, may have a positive effect on patients’ morbidity and survival. Related to the effect of periodontal treatment in CKD patients, an impressive threefold decrease in CRP in HD patients was reported to occur just after 4–6 weeks traditional periodontal therapy [16]. The comparison of data between baseline and third month post-periodontal treatment demonstrated a decline in clinical periodontal status and the improvement of CRP level as an inflammatory marker in our study. Significant positive correlations between CRP and periodontal status as well as for the alterations were also reported by Siribamrungwong et al. [17] who evaluated systemic responses following subsequent non-surgical and surgical periodontal treatments lasting more than 6 months in CAPD patients. Although the prevalence and severity of periodontitis were comparable in both studies, the length of evaluation was longer in
their study than in ours. However, the results of both studies showed successful periodontal treatment could have been achieved in PD with subsequent significant improvement in CRP levels. The presence of oral biofilm infection is not only related with local inflammatory reaction causing destruction of tooth supporting tissues but also provokes systemic inflammation [18]. In chronic renal disease, which affects the whole body, it is known that the periodontal tissues are adversely affected over time and that periodontitis is more frequent in CKD patients compared to healthy subjects [19]. Neglecting oral care due to the primary disease, disrupted metabolism of the periodontal tissues due to uremic toxins, and structural impairment of alveolar bone due to renal osteodystrophy could be the cofactors for the higher prevalence of periodontal disease in CKD patients [2–4]. In addition, this group of patients becomes more vulnerable to infections as a consequence of immunosuppression and malnutrition. Thus, local infections with systemic effects such as periodontitis can occur more frequently and readily [20].
123
Int Urol Nephrol Table 2 Comparison of parameters of demographic, biochemical, and periodontal among three groups according to severity of periodontal disease Parameters
White blood cell count (mm3) Hemoglobin (g/dL) Fasting glucose (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL) LDL cholesterol (mg/dL) HDL cholesterol (mg/dL) Serum calcium (mg/dL) Serum phosphorus (mg/dL) Serum albumin (g/dL) Transferrin saturation (%) hs-CRP(mg/L) Intact parathormon (pg/mL) Kt/vurea Plaque index Gingival index Pocket depth Bleeding on probing (%) Clinical attachment loss Gingival recession
Pre-treatment parameters
Post-treatment parameters
Healthy/ gingivitis (n = 22)
Slightly to moderate (n = 12)
Severe (n = 9)
6,716 ± 2,047a
9,007 ± 3,499
6,898 ± 1,107
11.8 ± 2.0
11.1 ± 2.2
93 (73–407)
Healthy/ gingivitis (n = 22)
Slightly to moderate (n = 12)
Severe (n = 9)
p value*
0.032
7,447 ± 1,937
8,820 ± 1,865
8,337 ± 1,849
0.137
12.2 ± 2.0
0.435
11.8 ± 1.6
12.5 ± 1.2
12.4 ± 1.6
0.374
114 (67–377)
102 (57–236)
0.352
93 (73–578)
86 (72–250)
86 (80–158)
0.802
187 ± 45
187 ± 35
188 ± 33
0.999
193 ± 75
188 ± 31
188 ± 32
0.968
150 (63–908)
162 (71–283)
243 (48–473)
0.260
155 (71–650)
164 (63–294)
285 (132–368)
0.199
109 ± 42
116 ± 34
109 ± 30
0.843
108 ± 57
112 ± 34
99 ± 35
0.827
38.7 ± 12.8
40.1 ± 13.4
32.0 ± 3.7
0.262
39 ± 13
41 ± 14
37 ± 9
0.829
8.7 ± 0.9
8.7 ± 0.7
8.7 ± 1.0
0.967
8.7 ± 0.8
8.9 ± 1.0
9.0 ± 1.2
0.728
4.2 ± 1.1
3.8 ± 1.0
4.0 ± 1.3
0.588
4.5 ± 2.1
4.3 ± 0.8
4.9 ± 1.4
0.770
3.1 ± 0.4
2.9 ± 0.4
3.2 ± 0.3
0.321
3.2 ± 0.6
3.2 ± 0.4
3.3 ± 0.3
0.758
28 ± 11
33 ± 15
30 ± 5
0.540
34 ± 14
31 ± 16
30 ± 6
0.690
5.6 (3.2–36.2)b 249 (25–1,067)
11.2 (3.2–38.3)** 248 (5–976)
26.2 (3.2–49.3)*** 387 (151–1,419)
0.01 0.379
4.0 (3.2–23.2) 225 (113–905)
5.6 (3.2–45.1) 382 (4–1,409)
15.3 (10.1–36.6) 195 (127–1,409)
0.012 0.914
2.3 2.5 1.4 2.1 0.5
2.5 3.0 2.0 2.7 0.7
1.8 3.0 2.0 4.4 0.8
2.1 2.4 1.3 2.5 0.4
(1.7–2.7) ± 0.4** ± 0.6 (1.2–5.6) (0–1.0)
0.380 0.134 0.290 0.082 0.364
(1.5–5.9) (1.0–3.0) (1.0–2.0)b (1.1–2.9)b (0.1–1.0)
(1.5–3.7) (1.0–3.0) (1.0–2.5) (1.6–4.0) (0.3–1.0)
p value*
(1.3–4.9) (2.1–3.0) (1.3–2.0) (2.6–5.8) (0–1.0)
0.292 0.122 0.003 \0.001 0.300
2.5 (1.3–5.9) 1.8 (1.0–2.7) ± 0.4 1.9 (1.1–3.2) 0.4 (0–1.0)
2.2 2.2 1.4 2.0 0.5
0.2 (0–1.1)
2.3 (1.2–3.8)**
3.8 (1.2–8.8)***
0.01
0 (-0.8–1.9)
0.3 (-0.7–1.6)
0.5 (0–4.6)
0.004
0 (0–0)b
3.2 (1.5–4.0)
5.9 (4.1–9.8)
\0.001
0 (0–0)b
0.1 (0–1.6)
0 (–0.4–4.3)
0.007
(1.8–4.9) ± 0.9** ± 0.5 (1.2–3.3) (0.1–1.0)
LDL low-density lipoprotein, HDL high-density lipoprotein, hs-CRP high-sensitivity C-reactive protein * Difference among the study groups ** Significant difference between pre- and post-treatment periods for slightly/moderate periodontitis group (p = 0.014) *** Significant difference between pre- and post-treatment periods for severe periodontitis group (p = 0.001) a Significant difference between healthy/gingivitis and slightly moderate periodontitis groups (p = 0.031) b Significant difference between healthy/gingivitis and slightly moderate (p = 0.023) and severe periodontitis groups (p \ 0.001)
It is known that periodontitis causes arteriosclerosis and related complications via low-level systemic inflammation and these adversely affect the survival rate of patients with
123
chronic renal failure undergoing peritoneal dialysis and hemodialysis. In fact, systemic inflammation and arteriosclerotic complications are decreased by effective
Int Urol Nephrol Table 3 Relationship between severity of periodontal disease and presence of cardiovascular disease (CVD)/diabetes mellitus (DM) Healthy and gingivitis n (%)
Slightly to moderate n (%)
Severe
p
n (%)
CVD Positive
14 (35.5)
9 (47.4)
8 (80.0)
Negative
25 (64.5)
10 (52.6)
2 (20.0)
Total
39 (100)
19 (100)
10 (100)
Positive
10 (25.5)
10 (52.6)
8 (80)
Negative
29 (74.5)
9 (47.4)
Total
39 (100)
19 (100)
0.028
DM 0.004
2 (20) 10 (100)
Table 4 Relationship between duration of peritoneal dialysis and number of peritonitis attacks in all patients median (25th and 75th percentiles) Groups
Duration (month) of peritoneal dialysis
Number of peritonitis attacks
Healthy and gingivitis (n = 39)
24 (12–64)
1 (0–5)
Slightly to moderate (n = 19)
48 (36–60)
2 (0–7)
Severe (n = 10)
56 (36–70)
2 (0–2)
p
0.003
0.235
periodontal therapy [21, 22], and several studies [9] suggest that not only can periodontitis increase inflammatory markers for CVD, such as CRP, but effective periodontal therapy can decrease CRP values. Hs-CRP is an extremely sensitive and non-specific acute phase marker for inflammation that is produced in response to many forms of tissue injury [23]. Although periodontitis is generally chronic in nature, acute phase elements, such as hs-CRP, are also part of the innate immunity response which has been determined in periodontitis [24, 25]. There is strong evidence from cross-sectional studies that plasma hs-CRP in periodontitis is increased compared with controls. There is modest evidence on the effect of periodontal therapy in lowering the levels of CRP [8]. Thus, it was plausible to establish a link between periodontitis and systemic inflammation. In this study, we found that the rate of periodontal disease was markedly higher and that hs-CRP values increased in parallel to severity of periodontitis in patients undergoing CAPD. After periodontal treatment, a significant decrease in hs-CRP level was observed in the control visit. Therefore, physicians should consider intraoral infections such as periodontitis if there was no known infectious focus such as otitis, peritonitis, cellulitis, or urinary tract infection in case of unexplained hs-CRP increase.
Several oral changes occur in patients with DM [26]. Although it is difficult to reach definitive conclusions regarding the specific effects of diabetes on the periodontium, severe gingival inflammation, deep periodontal pocket, rapid bone loss, and periodontal abscess occur more frequently in diabetic patients with poor oral hygiene [27, 28]. In recent studies, it has been suggested that there is an increased susceptibility to severe infections including periodontitis in patients with poorly controlled DM [29, 30]. It was reported that periodontal disease is relevant to complications of DM including neuropathy, nephropathy, retinopathy, and micro/macrovascular diseases [31, 32]. Finally, a bidirectional relationship between DM and periodontitis has been suggested by Iacopino [33]. More recently, higher serum hs-CRP levels and chronic periodontitis have been demonstrated in patients with cardiovascular disease [24, 25]. Indeed, the relation between CVD and CKD is well known [34]. The increasing prevalence of periodontal disease in peritoneal dialysis patients prompted us to investigate the temporal relation with inflammation to severity of periodontitis and the presence of CVD. Thus, it seems that periodontitis might be correlated with the presence of CVD in the CAPD population. According to our findings, there was a highly significant relation between the duration of peritoneal dialysis and severity of periodontal disease but not for the frequency of previous peritonitis attacks. Our findings are in agreement with the study published by Sekiguchi et al. [35] where the mean values for PD and CAL were statistically significantly higher in groups with longer (more than 3 years) duration compared to the group of\3 years. These data are also in agreement with the reports from Duran et al. [36] and Cengiz et al. [17] (who found a positive correlation between the length of time their subjects had been on HD and decrease in oral health status). The potential limitations of our study include limited sample size, presence of almost 40 % of dropouts, and higher prevalence of health/gingivitis within the follow-up group. Thus, there is need for further validation in a larger population with a control group. Also, there was a lack of usage of detailed inflammation markers and conventional methods to show the presence of CVD. The literature supports a bidirectional relation between CKD and periodontal disease. Patients with CKD have higher prevalence of periodontal disease while non-surgical periodontal therapy has been shown to decrease the systemic inflammatory burden in patients with CKD, especially in those undergoing dialysis therapy. Most of the trials conducted have observed the effect of periodontal therapy on hs-CRP levels. In conclusion, we aimed to re-assess periodontitis after diagnosis and management in a group of patients undergoing CAPD. We think that early recognition and treatment
123
Int Urol Nephrol
of periodontitis may contribute to improving the clinical course of CAPD and may target the reason for unexplained increased CRP level as a sign of systemic inflammation in patients undergoing peritoneal dialysis. Conflict of interest
None.
18.
19.
20.
References 1. Parkar SM, Ajithkrishnan CG (2012) Periodontal status in patients undergoing hemodialysis. Indian J Nephrol 22:246–250 2. Akar H, Akar GC, Carrero JJ et al (2011) Systemic consequences of poor oral health in chronic kidney disease patients. Clin J Am Soc Nephrol 6:218–226 3. Bayraktar G, Kurtulus I, Kazancioglu R et al (2009) Oral health and inflammation in patients with end-stage renal failure. Perit Dial Int 29:472–479 4. Nadeem M, Stephen L, Schubert C et al (2009) Association between periodontitis and systemic inflammation in patients with end-stage renal disease. SADJ 64:470–473 5. Siribamrungwong M, Puangpanngam K (2012) Treatment of periodontal diseases reduces chronic systemic inflammation in maintenance hemodialysis patients. Ren Fail 34:171–175 6. Proctor R, Kumar N, Stein A et al (2005) Oral and dental aspects of chronic renal failure. J Dent Res 84:199–208 7. Cengiz MI, Bal S, Go¨kc¸ay S et al (2007) Does periodontal disease reflect atherosclerosis in continuous ambulatory peritoneal dialysis patients? J Periodontol 78:1926–1934 8. Paraskevas S, Huizinga JD, Loos BG (2008) A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol 35:277–290 9. Craig RG, Kotanko P, Kamer AR et al (2007) Periodontal diseases—a modifiable source of systemic inflammation for the endstage renal disease patient on haemodialysis therapy? Nephrol Dial Transplant 22:312–315 10. Brito F, Almeida S, Figueredo CM et al (2012) Extent and severity of chronic periodontitis in chronic kidney disease patients. J Periodontal Res 47:426–430 11. Ismail G, Dumitriu HT, Dumitriu AS (2013) Periodontal disease: a covert source of inflammation in chronic kidney disease patients. Int J Nephrol 2013:515796 12. Chambrone L, Foz AM, Guglielmetti MR et al (2013) Periodontitis and chronic kidney disease: a systematic review of the association of diseases and the effect of periodontal treatment on estimated glomerular filtration rate. J Clin Periodontol 40:443–456 13. Fisher MA, Borgnakke WS, Taylor GW (2010) Periodontal disease as a risk marker in coronary heart disease and chronic kidney disease. Curr Opin Nephrol Hypertens 19:519–526 14. Lo¨e H (1967) The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol 38:610–616 15. Borawski J, Wilczyn´ska-Borawska M, Stokowska W et al (2007) The periodontal status of pre-dialysis chronic kidney disease and maintenance dialysis patients. Nephrol Dial Transplant 22:457–464 16. Kadiroglu AK, Kadiroglu ET, Sit D et al (2006) Periodontitis is an important and occult source of inflammation in hemodialysis patients. Blood Purif 24:400–404 17. Siribamrungwong M, Yothasamutr K, Puangpanngam K (2013) Periodontal treatment reduces chronic systemic inflammation in
123
21.
22.
23. 24.
25.
26.
27.
28. 29.
30.
31.
32.
33. 34.
35.
36.
peritoneal dialysis patients. Ther Apher Dial. doi:10.1111/17449987.12105 Grossi SG, Mealey BL, Rose LF (2004) Effect of periodontal infection on systemic health and well-being. In: Rose LF, Mealey BL, Genco RJ, Cohen DW (eds) Periodontics: medicine, surgery, and implants. Elsevier, Amsterdam, pp 846–859 Cengiz MI, Su¨mer P, Cengiz S et al (2009) The effect of the duration of the dialysis in hemodialysis patients on dental and periodontal findings. Oral Dis 15:336–341 El-Shinnawi U, Soory M (2013) Associations between periodontitis and systemic inflammatory diseases: response to treatment. Recent Pat Endocr Metab Immune Drug Discov 7:169–188 Paparello J, Kshirsagar A, Batlle D et al (2002) Comorbidity and cardiovascular risk factors in patients with chronic kidney disease. Semin Nephrol 22:494–506 Yeun JY, Levine RA, Mantadilok V et al (2000) C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis populations. Am J Kidney Dis 35:469–476 Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111:1805–1812 Persson GR, Ohlsson O, Pettersson T et al (2003) Chronic periodontitis, a significant relationship with acute myocardial infarction. Eur Heart J 24:2108–2115 Persson GR, Pettersson T, Ohlsson O et al (2005) High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis. J Clin Periodontol 32:219–224 Bascones-Martinez A, Matesanz-Perez P, Escribano-Bermejo M et al (2011) Periodontal disease and diabetes—review of the literature. Med Oral Patol Oral Cir Bucal 16:722–729 Newman MG, Takei HH, Carranza FA (2002) Influence of systemic disease and disorders on the periodontium. In: Klokkevold PR, Mealey BL, Carranza FA (eds) Carranza’s clinical periodontology, 9th edn. WB Saunders, Philadelphia, pp 208–209 Negrato CA, Tarzia O, Jovanovicˇ L et al (2013) Periodontal disease and DM. J Appl Oral Sci 21:1–12 Sastrowijoto S, van der Velden U, van Steenbergen T et al (1990) Improved metabolic control, clinical periodontal status, and subgingival microbiology in insulin-dependent DM. J Clin Periodontol 17:233–242 Karjalainen K, Knuuttila M (1996) The onset of diabetes and poor metabolic control increases gingival bleeding in children and adolescents with insulin-dependent DM. J Clin Periodontol 23:1060–1067 Taylor GW (2001) Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective. Ann Periodontol 6:99–112 Southerland JH, Taylor GW, Moss K et al (2000) Commonality in chronic inflammatory diseases: periodontitis, diabetes, and coronary artery disease. Periodontology 40:130–143 Iacopino AM (2001) Periodontitis and diabetes inter-relationships: role of inflammation. Ann Periodontol 6:125–137 Shoji T, Emoto M, Shinohara K et al (2001) Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease. J Am Soc Nephrol 12:2117–2124 Sekiguchi RT, Pannuti CM, Silva HT Jr et al (2012) Decrease in oral health may be associated with length of time since beginning dialysis. Spec Care Dentist 32:6–10 Duran I, Erdemir EO (2004) Periodontal treatment needs of patients with renal disease receiving haemodialysis. Int Dent J 54:274–278
