Q U I N T E S S E N C E I N T E R N AT I O N A L
ORAL MEDICINE
Karita Nylund
Oral health in predialysis patients with emphasis on periodontal disease Karita Nylund, DDS1/Jukka H. Meurman, MD, PhD, D Odont2/Anna Maria Heikkinen, DDS, PhD3/ Eero Honkanen, MD, PhD4/Maarit Vesterinen, DDS, MD, PhD3/Hellevi Ruokonen, DDS, PhD, MSc 5 Objective: Oral and periodontal infection load need to be treated in the predialysis stage among chronic kidney disease (CKD) patients in order to avoid later complications in dialysis or transplantation. Periodontal health was studied by specifically comparing diabetic nephropathy patients with those with other kidney disease. Method and Materials: This descriptive retrospective study comprised 144 predialysis patients (47 women), aged 23 to 83 years, examined at the Helsinki University Hospital, Finland. Of them, 52 (36%) had diabetic nephropathy. Oral and general health data, Periodontal Inflammatory Burden Index (PIBI), and Total Dental Index (TDI) were recorded from hospital records. Results were analyzed with cross tabulation, Pearson chi-square test, and binary logis-
tic regression with Wald test. Results: Of the diabetic nephropathy patients 39%, and of those with high A1C values 36%, respectively, had two or more sites with probing depths ≥ 6 mm compared with 19% in the other CKD group, and 18% of those with lower A1C values. TDI scores were high among 55% of the diabetic nephropathy patients. A1C values ≥ 6.5% associated with moderate periodontitis in 67%, and elevated PIBI in 62%. Conclusion: High A1C values associated with high oral infection burden indices. Diabetic nephropathy patients had more often high TDI scores and deep periodontal pockets compared with the other CKD patients. (Quintessence Int 2015;46:899–907; doi: 10.3290/j.qi.a34698)
Key words: chronic kidney disease (CKD), diabetes, glycosylated hemoglobin, periodontal disease, predialysis
An association between poor oral health and various systemic diseases and conditions has been observed. In addition to the much discussed cardiovascular diseases in this regard, chronic obstructive pulmonary disease, 1
PhD Student, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
2
Professor, Head Physician, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
3
Postdoctoral Researcher, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
4
Associate Professor, Chief Physician, Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
5
Deputy Chief Dentist, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Correspondence: Dr Karita Nylund, Specialist in Periodontology, Biomedicum Helsinki, Department of Oral and Maxillofacial Diseases, PO Box 63 (Haartmanninkatu 8), 00014 Helsinki, Finland. Email: karita. [email protected]
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chronic kidney disease (CKD), rheumatoid arthritis, obesity, metabolic syndrome, and even erectile dysfunction have also been studied.1,2 Periodontitis affects approximately half of the adults worldwide; the prevalence of severe periodontitis has been estimated to be up to 15% in many populations.3 This chronic bacterial infection is characterized by pro-inflammatory events thought indeed to play a role in a number of systemic diseases, but so far the association between periodontitis and other diseases does not imply causality.1 Kidneys play a major role in excretory, metabolic, and endocrine functions. Disturbances in kidney structure and function can lead to renal disease, defined as acute or chronic based on its duration (≤ 3 to > 3
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a
b
Figs 1a and 1b (a) Clinical photograph and (b) panoramic radiograph of a 58-year-old man with IgA nephropathy showing several foci of infections. These must be treated at latest at the predialysis stage among CKD patients.
months).4 CKD is an increasing public health concern worldwide, the prevalence being > 10% in many countries.4 CKD can be classified into glomerular, vascular, tubulointerstitial, cystic, and other congenital diseases, respectively. Reduced glomerular infiltration rate (GFR) and increased protein excretion (albumin) into urine are the classical sings of renal disease. In CKD, the GFR is < 60 mL/min per 1.73 m2 for > 3 months according to the National Kidney Foundation.4 Hypertension, diabetes, and obesity are the main causes of CKD in the developed countries.5,6 In Finland, diabetic nephropathy with end-stage renal disease is the most common cause to enter dialysis treatment.7 CKD patients are also considered potential future kidney transplantation candidates. Since infection is a significant cause in graft loss or death of the organ transplant patient, there is a need for diagnosing and treating the potential foci of infections early.8 In renal disease patients this means intervention at latest at the predialysis stage (Fig 1). Diabetes, especially when poorly controlled, also increases the risk of periodontitis.9,10 CKD patients with diabetes also have more dental caries and lower stimulated salivary flow rates than other CKD patients, rendering the patients liable to oral infections in general.11 Moderate to severe periodontitis may also predict the development of nephropathy and end-stage renal disease in type 2 diabetic patients.3,12 Oral and dental infections can therefore be particularly important sources of systemic inflammation in this patient group.13
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The present authors have previously published a descriptive study on oral health of CKD patients in general.11 Periodontal data were then reported by using the fairly crude World Health Organization (WHO) Community Periodontal Index for Treatment Needs. Therefore in the present study the periodontal status of the patients was analyzed in more detail. Records from diabetic nephropathy patients were compared with those from the other CKD patients with the hypothesis that periodontal health is poorer among diabetic nephropathy patients. It was also assumed that periodontal health is poorer in patients with higher glycosylated hemoglobin (A1C) values compared with patients with lower A1C values.
METHOD AND MATERIALS This study was a cross-sectional secondary analysis of 146 CKD patients aged 23 to 83 years in the predialysis stage. The clinical part of the study was carried out during 2000 and 2005 at the Departments of Oral and Maxillofacial Diseases, and Nephrology, of the Helsinki University Hospital, Finland. The patients underwent clinical and radiographic oral health examination by one specialist investigator (HR) with emphasis on recording all potential foci of infection. According to the current inclusion criteria, all predialysis patients had estimated GFR (eGFR) < 20 mL/ min/1.73 m2. This threshold corresponds the mid of CKD stage 4 (eGFR < 30 mL/min/1.73 m2) and stage 5
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(eGFR < 15 mL/min/1.73 m2), and is used as a definition for predialysis stage in our Department of Nephrology. Patients below this GFR threshold value are normally referred to dialysis and renal transplantation planning. Dialysis is usually started electively when GFR is less than 10% of normal (< 9 mL/min/1.73 m2). Exclusion criteria were children and young adults (< 18 years), pregnant or breastfeeding women, handicapped (physically or mentally disabled), and prisoners. Medical records and blood samples were available and the diagnosis of CKD had been set by a nephrologist. Diabetic nephropathy had been originally diagnosed either by renal biopsy or concomitant retinopathy associated with proteinuric renal disease. Patients underwent a full clinical and radiographic oral and periodontal examination including medical history. They also filled in a questionnaire regarding education, oral health home care, smoking habits, and symptoms of xerostomia. Education level and working status were reported in the previous publication in detail.11 Oral clinical examination was carried out by using the WHO criteria14 and decayed, missing, and filled teeth index (DMFT) was calculated. Caries lesions were recorded clinically and focus radiographs, including bite-wings, were taken when needed. Gingival recession, periodontal pocket depth (PPD), furcation lesions, signs of inflammation, and gingival overgrowth were recorded at six sites per tooth including third molars. A WHO-probe was used in measuring the PPD. Periodontal pockets had been recorded from six sites from each tooth, and were categorized as: • no periodontal pocket • one or more sites with probing depths ≥ 4 mm • further 0 to 1 sites with ≥ 6 mm deep periodontal pocket • two or more sites with ≥ 6 mm deep periodontal pockets. According to the Center for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP), severe periodontitis is defined as two or more teeth with clinical attachment loss (CAL) ≥ 6 mm at interproximal sites and one or more teeth with
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PPD ≥ 5 mm at interproximal sites. Moderate periodontitis is classified as two or more teeth with CAL ≥ 4 mm at interproximal sites, or two or more teeth with PPD ≥ 5 mm at interproximal sites. Cases that do not fulfil the criteria for moderate/severe disease are classified as mild/no periodontitis.15 A furcation probe was used in classifying furcation lesions according to Hamp et al16 as stage I, II, or III, respectively, illustrating the loss of periodontal support in the furcation area. Diastemas, mobility of teeth, signs of mucosal lesions, dental erosions, attritions, and abrasions were also recorded. Of the 146 predialysis patients, the periodontal statuses of two patients were missing in the hospital records and thus the severity of periodontitis could be studied in 144 patients. Panoramic radiographic analyses were available from 127 patients. Alveolar bone loss was measured from each tooth in the cervical, middle, and apical thirds of the roots by a specialist in oral radiology in the hospital. The radiographs were further analyzed by sextants and the maximal horizontal and vertical bone loss in each sextant was recorded. Maximal alveolar bone loss in any sextant was reported as “yes” or “no” in relation to the root lengths. Total Dental Index (TDI)17 and Periodontal Inflammatory Burden Index (PIBI)18 were calculated to describe the total degree of oral inflammation. Table 1 gives the details of TDI and PIBI, respectively. TDI and PIBI scores were classified into two groups by median distribution and values compared between the diabetic nephropathy and the other CKD groups, and between the patients with A1C values lower or higher than 6.5% (48 mmol/mol), respectively. The study was approved by the Ethical Committee of the Helsinki and Uusimaa Hospital District (Dnro305/13/03/02/2012) and registered in the hospital database for clinical trials. Informed consent was obtained from all the patients.
Statistical analyses SPSS statistical program version 21 was used to perform statistical analyses. Results were analyzed with cross-tabulation and Pearson chi-square test by com-
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Table 1
Determination of TDI (32 teeth) and PIBI (28 teeth)
Type of disease
Score No caries lesions
0
1–3 caries lesions
1
4–7 caries lesions or no teeth in maxilla or mandible
2
≥ 8 caries lesions or relics or no teeth
3
Caries
Periodontitis
Periapical lesions
4–5 mm deep gingival pocket
1
≥ 6 mm deep gingival pocket
2
Pus in gingival pocket
3
1 periapical lesion or vertical bone pocket or both
1
2 periapical lesions
2
≥ 3 periapical lesions
3
Absent
0
Present
1
Pericoronitis PIBI = Ʃ (Nmod PPD + 2Nadv PPD). Nmod, number of sites with moderate periodontal lesions (4–5 mm). Nadv, number of sites with advanced periodontal lesions (≥ 6 mm).
146 patients
93 other kidney diseases (60 men, 33 women)
53 diabetic nephropathy (38 men, 15 women)
1 periodontal status missing 92 other kidney disease (59 men, 33 women)
1 periodontal status missing 52 diabetic nephropathy (38 men, 14 women)
Total 144 CKD patients (with clinical periodontal status)
Fig 2
Study profile.
paring the diabetic nephropathy group with the other kidney disease group, and patients with lower A1C values (< 6.5%) with higher (≥ 6.5%) A1C values, respectively. The percentages of different variables were compared. A1C values were compared by means between the diabetic nephropathy group and other kidney disease group by independent samples t test as appropriate. Multivariate analyses with covariates sex, age, smoking, PIBI, TDI, and deep periodontal pockets
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(two or more teeth with PPD ≥ 5 mm and two or more sites with ≥ 6 mm) were conducted using binary logistic regression with Wald test regarding the A1C values.
RESULTS Periodontal disease Of the 146 patients, 53 had diabetic nephropathy (30 [20.5%] DM I, 23 [15.8%] DM II), while 93 (63.7%) had
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Table 2
Basic characteristics of the patients
Age (mean ± SD; years)
Diabetic nephropathy, n = 52 (36%)
Other kidney disease, n = 92 (64%)
DM I (30), DM II (22)
CKD total, N = 144 (100%)
P*
55 ± 12.5
52 ± 13.5
54 ± 12.9
.170
Men
59 (64.1%)
38 (73.1%)
97 (67.4%)
Women
33 (35.9%)
14 (26.9%)
47 (32.6%)
Current smoker
22 (31.4%)
11 (32.4%)
33 (31.7%)
Nonsmoker
48 (68.6%)
23 (67.6%)
71 (68.3%)
Sex
.271
Smoking†
.924
A1C (%)‡ (mean ± SD)
5.7 ± 0.8, N = 63
8.2 ± 1.6, N = 52
6.8 ± 1.8
< 6.5% (< 48 mmol/mol)
55 (87.3%)
5 (9.6%)
60 (52.2%)
≥ 6.5% (≥ 48 mmol/mol)
8 (12.7%)
47 (90.4%)
55 (47.8%)
< .001 < .001
*P value (unadjusted) obtained from Pearson χ2 and independent-sample t test (Mann-Whitney test) when comparing mean age and mean A1C (%). †104 smoking status included, exsmokers (n = 32) were excluded, 8 smoking status missing. ‡A1C (%) available from 115 patients.
other CKD, respectively. As shown in Fig 2, periodontal pockets were measured from 144 patients. Only one patient had no specific diagnosis for kidney failure. The other CKD diagnoses included among others polycystic kidney disease (n = 31), nephrosclerosis (n = 16), immunoglobulin A (IgA)-nephropathy (n = 13), focal segmental glomerulosclerosis (n = 9), and membranous glomerulonephritis (n = 4). Mean A1C was 5.7% (± 0.8) in the other CKD group, and 8.2% (± 1.6) in the diabetic nephropathy group (P < .001). Table 2 gives basic characteristics of the patients. No statistically significant differences were found between the background variables other than in the working status.11 In general, the prevalence of periodontal disease (PPD ≥ 4 mm) was high among the CKD patients (88%). This was diagnosed in 90% of the diabetic nephropathy patients and in 87% of the other CKD patients, respectively. This result was not statistically significant, however (Table 3). Comparing the different PPDs, the diabetic nephropathy group had more often two or more teeth with PPD ≥ 5 mm than the other CKD group. This defines moderate periodontitis according to the CDC/ AAP (Table 3). When comparing the different A1C values, however, patients with higher A1C values associated with moderate periodontitis more often (67%) than patients with lower A1C values (40%), respectively (P < .005)
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(Table 4). Of the diabetic nephropathy patients 39% (or patients with higher A1C 36%) had two or more sites with PPD ≥ 6 mm compared with 19% of the other CKD patients (or 18% with lower A1C values), and patients with only 0 to 1 sites with ≥ 6 mm PPD were more common in the other CKD group, and with lower A1C values (82%), than in the diabetic nephropathy group (62%) or with higher A1C values (64%), respectively (P < .05) (Tables 3 and 4). There was no statistically significant difference in the prevalence of furcation lesions between the different subgroups. A Class I furcation lesion was found in 25% of CKD patients, a Class II lesion in 14%, and a Class III lesion in 4% of CKD patients.
Radiographic examination Maximum alveolar bone loss was investigated from each sextant in the panoramic radiographs. In general, alveolar bone loss (vertical or horizontal) was common in the CKD patients. Bone loss up to cervical thirds of root lengths was observed in 54%, while alveolar bone loss up to middle thirds was observed in 31%. Apical thirds of root lengths was found in 12% of the CKD patients (Table 3). There was no statistically significant difference in bone loss when comparing the different CKD diagnoses or when comparing the different A1C values, respectively (Tables 3 and 4).
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Table 3
Periodontal status parameters
Parameter
Other CKD, n = 92 (64%)
Diabetic nephropathy, n = 52 (36%)
CKD total, N = 144 (100%)
P*
Number of teeth, median ± SD
26 ± 8.1
24 ± 7.3
25 ± 7.8
.144
No periodontal pocket/subject
12 (13.0%)
5 (9.6%)
17 (11.8%)
≥ 1 site with ≥ 4 mm PPD
80 (87.0%)
47 (90.4%)
127 (88.2%)
0–1 teeth with ≥ 5 mm deep PPD†
48 (52.2%)
20 (38.5%)
68 (47.2%)
≥ 2 teeth with ≥ 5 mm deep PPD
44 (47.8%)
32 (61.5%)
76 (52.8%)
0–1 site with ≥ 6 mm deep PPD
75 (81.5%)
32 (61.5%)
107 (74.3%)
≥ 2 sites with ≥ 6 mm deep PPD
17 (18.5%)
20 (38.5%)
37 (25.7%)
Yes
46 (54.1%)
23 (54.8%)
69 (54.3%)
No
39 (45.9%)
19 (45.2%)
58 (45.7%)
Yes
25 (29.4%)
14 (33.3%)
39 (30.7%)
No
60 (70.6%)
28 (66.7%)
88 (69.3%)
Yes
9 (10.6%)
6 (14.3%)
15 (11.8%)
No
76 (89.4%)
36 (85.7%)
112 (88.2%)
PIBI (0–5)
50 (54.3%)
23 (44.2%)
73 (50.7%)
PIBI (6–111)
42 (45.7%)
29 (55.8%)
71 (49.3%)
TDI (0–3)§
55 (64.7%)
19 (45.2%)
74 (58.3%)
TDI (4–10)
30 (35.3%)
23 (54.8%)
53 (41.7%)
.540
.113
.008
Cervical Maximum bone loss‡
.945
Middle
.652
Apical
.544
.243
.036 *P value (unadjusted) obtained from Pearson χ2 test and Mann-Whitney when comparing median number of teeth. Bold indicates statistical significance (P < .05). †Moderate periodontitis case definition according to the CDC/AAP. ‡Maximum bone loss of root lengths (horizontal or vertical) in any sextant. §Panoramic radiograph available from 127/144 (17 missing).
PIBI Patients with higher A1C values showed higher PIBI scores (PIBI 6 to 111 in 62%) compared with patients with lower A1C (PIBI 6 to 111 in 40%; P < .05) (Table 4).
pared with the other CKD group (35%) (P < .05) (Table 3). Higher A1C values associated with higher TDI scores (4 to 10 in 51%) when compared with patients with lower A1C values (4 to 10 in 41%), but the result was not statistically significant (Table 4).
Smoking Smokers were divided into two groups, namely current and nonsmokers, while exsmokers were excluded. Smokers had statistically significant higher TDI values (P < .05). No statistically significant difference was observed in the effect of smoking on the subjects with higher A1C, and severity of periodontitis, or high PIBI scores, respectively.
TDI TDI and A1C values were available from only 99 patients. Diabetic nephropathy diagnosis associated more often with higher TDI scores (4 to 10 in 55%) com-
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Multivariate analyses According to multivariate analyses no variable seemed to be significant to A1C values (Table 5).
DISCUSSION The main finding in the present study was that periodontal disease indeed was prevalent in predialysis CKD patients and that high oral infection burden (assessed by using deep PPD, the PIBI, and TDI scorings) was associated with poor metabolic control among these patients. Diabetic nephropathy patients or patients
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Table 4
A1C’s association on number of periodontal pockets, alveolar bone loss, PIBI, and TDI A1C < 6.5% (< 48 mmol/ mol), n = 60 (42%)†
A1C ≥ 6.5% (≥ 48 mmol/ mol), n = 55 (38%)†
Total, N = 115
P*
Number of teeth, median ± SD
25 ± 8.7
24 ± 7.1
25 ± 7.8
.688
No periodontal pockets/subject
7 (11.7%)
5 (9.1%)
12 (10.4%)
≥ 4 mm PPD
53 (88.3%)
50 (90.9%)
103 (89.6%)
0–1 teeth with ≥ 5 mm deep pocket
36 (60.0%)
18 (32.7%)
54 (47.0%)
≥ 2 teeth with ≥ 5 mm deep pockets
24 (40.0%)
37 (67.3%)
61 (53.0%)
0–1 sites with ≥ 6 mm deep pocket
49 (81.7%)
35 (63.6%)
84 (73.0%)
≥ 2 sites with ≥ 6 mm deep pockets
11 (18.3%)
20 (36.4%)
31 (27.0%)
.652
.003
.030 Yes
31 (57.4%)
25 (55.6%)
56 (56.6%)
No
23 (42.6%)
20 (44.4%)
43 (43.4%)
Yes
17 (31.5%)
15 (33.3%)
32 (32.3%)
No
37 (68.5%)
30 (66.7%)
67 (67.7%)
Cervical Maximum bone loss‡
.853
Middle
.844 Yes
6 (11.1%)
7 (15.6%)
13 (13.1%)
No
48 (88.9%)
38 (84.4%)
86 (86.9%)
PIBI (0–5)
36 (60.0%)
21 (38.2%)
57 (49.6%)
PIBI (6–111)
24 (40.0%)
34 (61.8%)
58 (50.4%)
TDI (0–3)§
32 (59.3%)
22 (48.9%)
54 (54.5%)
TDI (4–10)
22 (40.7%)
23 (51.1%)
45 (45.5%)
Apical
.514
.019
.302 *P value (unadjusted) obtained from Pearson χ2 test and Mann-Whitney when comparing median number of teeth. Bold indicates statistical significance (P < .05) †A1C (%) available from 115 patients (29 missing). Panoramic radiograph analysis available from 127/144 (17 missing). ‡Maximum bone loss of root lengths (horizontal or vertical) in any sextant. §Both A1C (%) and panoramic radiograph analysis available from 99 patients (see maximal bone loss and TDI).
Table 5
Variables affecting A1C levels (odds ratios and 95% confidence intervals [CI] based on logistic regression)
Independent variables
A1C values ≥ 6.5%* (n = 33), P†
OR (95% CI)
.789
1.2 (0.4–3.6)
.562
1.4 (0.5–4.0)
.152
0.4 (0.2–1.4)
.216
0.4 (0.1–1.6)
.419
0.6 (0.2–2.0)
.632
0.7 (0.2–2.9)
.615
0.7 (0.2–2.9)
Male Sex Female‡ ≤ 54 y Age, median > 55 y‡ Current smokers Smoking Nonsmokers‡ 0–5 PIBI 6–111‡ 0–3 TDI 4–10‡ 0–1 sites with ≥ 6 mm PPD PPD ≥ 2 sites with ≥ 6 mm PPD‡ 0–1 teeth with ≥ 5 PPD Moderate periodontitis ≥ 2 teeth with ≥ 6 mm PPD‡ *The reference category is 0–6.4. †P value obtained from Wald test. ‡This parameter is set to zero because it is redundant.
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with high A1C values in general showed poorer periodontal health as expected. The results thus confirmed the study hypotheses. The review by Chambrone et al19 concludes that there is enough evidence to support the association between periodontitis and CKD. Earlier studies have also shown an association between poor metabolic control (high A1C values) and suboptimal periodontal treatment outcome.20 Reasons for the association between periodontitis and CKD are explained by uremia with subsequent impaired immune system which results in decreased host response, intense psychologic burden among the patients, hyperparathyroidism, or diabetes.21 In general, there is a well-known two-way relationship between periodontitis and diabetes, and poor periodontal health may exacerbate glycemic control, and vice versa.22,23 This should be taken into account when treating CKD patients. Periodontal treatment as such can improve glycemic control; improvement of A1C level by 0.4% has been subsequently reported.24-26 Periodontitis increases chronic systemic inflammatory burden through pro-inflammatory cytokines and by invasion of bacteria and their products to bloodstream. Periodontal disease could even be considered as a non-traditional risk factor for CKD.27 A study by Kshirsagar et al28 found an association with antibodies to the periodontal pathogens Porphyromonas gingivalis, Treponema denticola, Aggregatibacter actinomycetemcomitans and CKD. In the present study, the focus was the number of periodontal deep pockets, radiologic bone loss, and the number of caries, periapical, and pericoronitis lesions. The limitation of the present retrospective study is that bleeding on probing results, Plaque Index, or CAL values could not be taken into account, since these parameters had not been reported systematically in all patients. Lack of data made it impossible to use the thorough definition for severe (or mild) periodontitis according to CDC/AAP.15 Hence only the definition for moderate periodontitis (two or more teeth with PPD 5 mm or deeper) could be used. The PIBI score reflects the subgingival inflammatory area better than CAL,
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however. A limitation of the study was also that alveolar bone loss was measured only from panoramic radiographs while caries lesions were recorded at clinical examination. However, focused radiographs were taken when needed. Another limitation was that other diseases or drugs used by the patients were not taken into account. These aspects were given in more detail in the previous study by Vesterinen et al.11 A further limitation was that there was no healthy control group in the original study, as well as the slightly small size of the data due to practical reasons. These weaknesses could thus not be avoided due to the nature of the investigation. In the present study a statistically significant difference was found between the different subgroups of CKD and between the different A1C values by comparing deep periodontal pockets, TDI, and PIBI scores, respectively. TDI is the sum of severity of dental diseases and was used for a holistic approach in the measuring of mouth-derived infection burden, not only that of periodontitis. This index was originally used by Mattila et al17 in assessing the link between poor dental health and coronary heart disease. The index has since been well documented. Smoking has been associated with both periodonti29,30 tis and CKD.31 A study by Hallan and Orth32 showed in a Norwegian population that current smokers had 4.0 times higher and former smokers 3.3 times higher risk for kidney failure than never smokers, respectively. In the present study, however, no effect of smoking other than on higher TDI values could be found. Many predialysis patients are potential dialysis patients and prospective kidney transplant recipients. Treating all infections is especially important in patients who will later have an organ transplant with subsequently higher risk of post-transplant complications.8 The future aim is to follow patients through dialysis and up to the kidney transplant phase. Finally, the present study gives, for the first time, information about oral health among predialysis CKD patients. The results could benefit the whole health care cycle of CKD patients especially in hospital units. Hence the present findings may also offer hypothesis generation for further treatment studies.
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CONCLUSION Studies of the association between periodontitis and CKD have mainly investigated patients on maintenance hemodialysis. Findings on predialysis stage patients of different CKD etiology are reported herein. The results showed that diabetic nephropathy patients had more often deep periodontal pockets, and higher TDI scores, compared with the other CKD patients, and that A1C levels ≥ 6.5% (≥ 48 mmol/mol) associated with more severe oral infection burden than lower A1C levels < 6.5% (< 48 mmol/mol). Many of these predialysis patients are potential prospective dialysis patients and kidney transplant recipients. Therefore oral and particularly periodontal infection could be an important source of systemic inflammation and should subsequently be diagnosed and treated on time.
ACKNOWLEDGMENT This study was funded by hospital research funding (EVO TYH20012128), Finnish Women Dentists’ Association, and by the Finnish Dental Society Apollonia.
REFERENCES 1. Linden GJ, Lyons A, Scannapieco FA. Periodontal systemic associations: review of the evidence. J Clin Periodontol 2013;40(Suppl 14):S8–S19. 2. Zadik Y, Bechor R, Galor S, Justo D, Heruti RJ. Erectile dysfunction might be associated with chronic periodontal disease: two ends of the cardiovascular spectrum. J Sex Med 2009;6:1111–1116. 3. Chapple ILC, Genco R and on behalf of working group 2 of the joint EFP/AAP workshop. Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol 2013;40(Suppl 14):S106–S112. 4. Eckardt K-U, Coresh J, Devuyst O, et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 2013;382:158–169. 5. Cignarelli M, Lamacchia O. Obesity and kidney disease. Nutr Metab Cardiovasc Dis 2007;17:757–762. 6. Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet 2013;382:260–272. 7. Saha H. Krooninen munuaisten vajaatoiminta (uremia). Available at: http:// www.terveyskirjasto.fi Lääkärikirja Duodecim. Accessed: 20 Aug 2012. 8. Helenius-Hietala J, Åberg F, Meurman JH, Isoniemi H. Increased infection risk post liver transplant without pretransplant dental treatment. Oral Dis 2013;19:271–278. 9. Mealey BL, Oates TW. Diabetes mellitus and periodontal diseases. J Periodontol 2006;77:1289–1303.
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10. Nagasawa T, Noda M, Katagiri S, et al. Relationship between periodontitis and diabetes: importance of a clinical study to prove the vicious cycle. Inter Med 2010;49:881–885. 11. Vesterinen M, Ruokonen H, Furuholm J, Honkanen E, Meurman JH. Oral health in predialysis patients with emphasis on diabetic nephropathy. Clin Oral Invest 2011;15:99–104. 12. Shultis WA, Weil EJ, Looker HC, et al. Effect of periodontitis on overt nephropathy and end-stage renal disease in type 2 diabetes. Diabetes Care 2007;30:306–311. 13. Bayraktar G, Kurtulus I, Kazancioglu R, et al. Oral health and inflammation in patients with end-stage renal failure. Perit Dial Int 2009;29:472–479. 14. World Health Organization (1997). Oral health surveys - basic methods, 4th edn. Geneva: World Health Organization. Available at: http://www.paho.org/ hq/dmdocuments/2009/OH_st_Esurv.pdf. 15. Page RC, Eke PI. Case definitions for use in population-based surveillance of periodontitis. J Periodontol 2007;78:1387–1399. 16. Hamp SE, Nyman S, Lindhe J. Periodontal treatment of multirooted teeth. Results after 5 years. J Clin Periodontol 1975;2:125–135. 17. Mattila KJ, Nieminen MS, Valtonen VV, et al. Association between dental health and acute myocardial infarction. Br Med J 1989;298:779–781. 18. Lindy O, Suomalainen K, Mäkelä M, Lindy S. Statin use is associated with fewer periodontal lesions: a retrospective study. BMC Oral Health 2008;8:16. 19. Chambrone L, Foz AM, Guglielmetti MR, et al. 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 2013;40:443–456. 20. Tonetti MS, Claffey N, on behalf of the European Workshop in Periodontology group C. Advances in the progression of periodontitis and proposal of definitions of a periodontitis case and disease progression for use in risk factor research. J Clin Periodontol 2005;32(Suppl 6):210–213. 21. Ismail G, Dumitriu HT, Dumitriu AS, Ismail FB. Periodontal disease: a covert source of inflammation in chronic kidney disease patients. Int J Nephrol 2013;2013:515796. 22. Preshaw PM, Alba AL, Herrera D, et al. Periodontitis and diabetes: a two-way relationship. Diabetologia 2012;55:21–31. 23. Grossi SG, Zambon JJ, Ho AW, et al. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol 1994;65:260–267. 24. Janket S-J, Wightman A, Baird AE, Van Dyke TE, Jones JA. Does periodontal treatment improve glycemic control in diabetic patients? A meta-analysis of intervention studies. J Dent Res 2005;84:1154–1159. 25. Teeuw WJ, Gerdes, VEA, Loos BG. Effect of periodontal treatment on glycemic control of diabetic patients. A systematic review and meta-analysis. Diabetes Care 2010;33:421–427. 26. Telgi RL, Tandon V, Tangade PS, Tirth A, Kumar S, Yadav V. Efficacy of nonsurgical periodontal therapy on glycaemic control in type II diabetic patients: a randomized controlled clinical trial. J Periodontal Implant Sci 2013;43:177–182. 27. Fisher MA, Taylor GW, Shelton BJ, et al. Periodontal disease and other nontraditional risk factors for CKD. Am J Kidney Dis 2007;51:45–52. 28. Kshirsagar AV, Offenbacher S, Moss KL, Barros SP, Beck JD. Antibodies to periodontal organisms are associated with decreased kidney function. The dental atherosclerosis risk in communities study. Blood Purif 2007;25:125–132. 29. Kinane DF, Marshall GJ. Periodontal manifestations of systemic disease. Aust Dent J 2001;46:2–12. 30. Heasman L, Stacey F, Preshaw PM, McCracken GI, Hepburn S, Heasman PA. The effect of smoking on periodontal treatment response: a review of clinical evidence. J Clin Periodontol 2006;33:241–253. 31. Haroun MK, Jaar BG, Hoffman SC, Comstock GW, Klag MJ, Coresh J. Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol 2003;14:2934–2941. 32. Hallan SI, Orth SR. Smoking is a risk factor in the progression to kidney failure. Kidney Int 2011;80:516–523.
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ORAL MEDICINE
Karita Nylund
Oral health in predialysis patients with emphasis on periodontal disease Karita Nylund, DDS1/Jukka H. Meurman, MD, PhD, D Odont2/Anna Maria Heikkinen, DDS, PhD3/ Eero Honkanen, MD, PhD4/Maarit Vesterinen, DDS, MD, PhD3/Hellevi Ruokonen, DDS, PhD, MSc 5 Objective: Oral and periodontal infection load need to be treated in the predialysis stage among chronic kidney disease (CKD) patients in order to avoid later complications in dialysis or transplantation. Periodontal health was studied by specifically comparing diabetic nephropathy patients with those with other kidney disease. Method and Materials: This descriptive retrospective study comprised 144 predialysis patients (47 women), aged 23 to 83 years, examined at the Helsinki University Hospital, Finland. Of them, 52 (36%) had diabetic nephropathy. Oral and general health data, Periodontal Inflammatory Burden Index (PIBI), and Total Dental Index (TDI) were recorded from hospital records. Results were analyzed with cross tabulation, Pearson chi-square test, and binary logis-
tic regression with Wald test. Results: Of the diabetic nephropathy patients 39%, and of those with high A1C values 36%, respectively, had two or more sites with probing depths ≥ 6 mm compared with 19% in the other CKD group, and 18% of those with lower A1C values. TDI scores were high among 55% of the diabetic nephropathy patients. A1C values ≥ 6.5% associated with moderate periodontitis in 67%, and elevated PIBI in 62%. Conclusion: High A1C values associated with high oral infection burden indices. Diabetic nephropathy patients had more often high TDI scores and deep periodontal pockets compared with the other CKD patients. (Quintessence Int 2015;46:899–907; doi: 10.3290/j.qi.a34698)
Key words: chronic kidney disease (CKD), diabetes, glycosylated hemoglobin, periodontal disease, predialysis
An association between poor oral health and various systemic diseases and conditions has been observed. In addition to the much discussed cardiovascular diseases in this regard, chronic obstructive pulmonary disease, 1
PhD Student, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
2
Professor, Head Physician, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
3
Postdoctoral Researcher, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
4
Associate Professor, Chief Physician, Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
5
Deputy Chief Dentist, Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Correspondence: Dr Karita Nylund, Specialist in Periodontology, Biomedicum Helsinki, Department of Oral and Maxillofacial Diseases, PO Box 63 (Haartmanninkatu 8), 00014 Helsinki, Finland. Email: karita. [email protected]
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chronic kidney disease (CKD), rheumatoid arthritis, obesity, metabolic syndrome, and even erectile dysfunction have also been studied.1,2 Periodontitis affects approximately half of the adults worldwide; the prevalence of severe periodontitis has been estimated to be up to 15% in many populations.3 This chronic bacterial infection is characterized by pro-inflammatory events thought indeed to play a role in a number of systemic diseases, but so far the association between periodontitis and other diseases does not imply causality.1 Kidneys play a major role in excretory, metabolic, and endocrine functions. Disturbances in kidney structure and function can lead to renal disease, defined as acute or chronic based on its duration (≤ 3 to > 3
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a
b
Figs 1a and 1b (a) Clinical photograph and (b) panoramic radiograph of a 58-year-old man with IgA nephropathy showing several foci of infections. These must be treated at latest at the predialysis stage among CKD patients.
months).4 CKD is an increasing public health concern worldwide, the prevalence being > 10% in many countries.4 CKD can be classified into glomerular, vascular, tubulointerstitial, cystic, and other congenital diseases, respectively. Reduced glomerular infiltration rate (GFR) and increased protein excretion (albumin) into urine are the classical sings of renal disease. In CKD, the GFR is < 60 mL/min per 1.73 m2 for > 3 months according to the National Kidney Foundation.4 Hypertension, diabetes, and obesity are the main causes of CKD in the developed countries.5,6 In Finland, diabetic nephropathy with end-stage renal disease is the most common cause to enter dialysis treatment.7 CKD patients are also considered potential future kidney transplantation candidates. Since infection is a significant cause in graft loss or death of the organ transplant patient, there is a need for diagnosing and treating the potential foci of infections early.8 In renal disease patients this means intervention at latest at the predialysis stage (Fig 1). Diabetes, especially when poorly controlled, also increases the risk of periodontitis.9,10 CKD patients with diabetes also have more dental caries and lower stimulated salivary flow rates than other CKD patients, rendering the patients liable to oral infections in general.11 Moderate to severe periodontitis may also predict the development of nephropathy and end-stage renal disease in type 2 diabetic patients.3,12 Oral and dental infections can therefore be particularly important sources of systemic inflammation in this patient group.13
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The present authors have previously published a descriptive study on oral health of CKD patients in general.11 Periodontal data were then reported by using the fairly crude World Health Organization (WHO) Community Periodontal Index for Treatment Needs. Therefore in the present study the periodontal status of the patients was analyzed in more detail. Records from diabetic nephropathy patients were compared with those from the other CKD patients with the hypothesis that periodontal health is poorer among diabetic nephropathy patients. It was also assumed that periodontal health is poorer in patients with higher glycosylated hemoglobin (A1C) values compared with patients with lower A1C values.
METHOD AND MATERIALS This study was a cross-sectional secondary analysis of 146 CKD patients aged 23 to 83 years in the predialysis stage. The clinical part of the study was carried out during 2000 and 2005 at the Departments of Oral and Maxillofacial Diseases, and Nephrology, of the Helsinki University Hospital, Finland. The patients underwent clinical and radiographic oral health examination by one specialist investigator (HR) with emphasis on recording all potential foci of infection. According to the current inclusion criteria, all predialysis patients had estimated GFR (eGFR) < 20 mL/ min/1.73 m2. This threshold corresponds the mid of CKD stage 4 (eGFR < 30 mL/min/1.73 m2) and stage 5
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(eGFR < 15 mL/min/1.73 m2), and is used as a definition for predialysis stage in our Department of Nephrology. Patients below this GFR threshold value are normally referred to dialysis and renal transplantation planning. Dialysis is usually started electively when GFR is less than 10% of normal (< 9 mL/min/1.73 m2). Exclusion criteria were children and young adults (< 18 years), pregnant or breastfeeding women, handicapped (physically or mentally disabled), and prisoners. Medical records and blood samples were available and the diagnosis of CKD had been set by a nephrologist. Diabetic nephropathy had been originally diagnosed either by renal biopsy or concomitant retinopathy associated with proteinuric renal disease. Patients underwent a full clinical and radiographic oral and periodontal examination including medical history. They also filled in a questionnaire regarding education, oral health home care, smoking habits, and symptoms of xerostomia. Education level and working status were reported in the previous publication in detail.11 Oral clinical examination was carried out by using the WHO criteria14 and decayed, missing, and filled teeth index (DMFT) was calculated. Caries lesions were recorded clinically and focus radiographs, including bite-wings, were taken when needed. Gingival recession, periodontal pocket depth (PPD), furcation lesions, signs of inflammation, and gingival overgrowth were recorded at six sites per tooth including third molars. A WHO-probe was used in measuring the PPD. Periodontal pockets had been recorded from six sites from each tooth, and were categorized as: • no periodontal pocket • one or more sites with probing depths ≥ 4 mm • further 0 to 1 sites with ≥ 6 mm deep periodontal pocket • two or more sites with ≥ 6 mm deep periodontal pockets. According to the Center for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP), severe periodontitis is defined as two or more teeth with clinical attachment loss (CAL) ≥ 6 mm at interproximal sites and one or more teeth with
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PPD ≥ 5 mm at interproximal sites. Moderate periodontitis is classified as two or more teeth with CAL ≥ 4 mm at interproximal sites, or two or more teeth with PPD ≥ 5 mm at interproximal sites. Cases that do not fulfil the criteria for moderate/severe disease are classified as mild/no periodontitis.15 A furcation probe was used in classifying furcation lesions according to Hamp et al16 as stage I, II, or III, respectively, illustrating the loss of periodontal support in the furcation area. Diastemas, mobility of teeth, signs of mucosal lesions, dental erosions, attritions, and abrasions were also recorded. Of the 146 predialysis patients, the periodontal statuses of two patients were missing in the hospital records and thus the severity of periodontitis could be studied in 144 patients. Panoramic radiographic analyses were available from 127 patients. Alveolar bone loss was measured from each tooth in the cervical, middle, and apical thirds of the roots by a specialist in oral radiology in the hospital. The radiographs were further analyzed by sextants and the maximal horizontal and vertical bone loss in each sextant was recorded. Maximal alveolar bone loss in any sextant was reported as “yes” or “no” in relation to the root lengths. Total Dental Index (TDI)17 and Periodontal Inflammatory Burden Index (PIBI)18 were calculated to describe the total degree of oral inflammation. Table 1 gives the details of TDI and PIBI, respectively. TDI and PIBI scores were classified into two groups by median distribution and values compared between the diabetic nephropathy and the other CKD groups, and between the patients with A1C values lower or higher than 6.5% (48 mmol/mol), respectively. The study was approved by the Ethical Committee of the Helsinki and Uusimaa Hospital District (Dnro305/13/03/02/2012) and registered in the hospital database for clinical trials. Informed consent was obtained from all the patients.
Statistical analyses SPSS statistical program version 21 was used to perform statistical analyses. Results were analyzed with cross-tabulation and Pearson chi-square test by com-
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Table 1
Determination of TDI (32 teeth) and PIBI (28 teeth)
Type of disease
Score No caries lesions
0
1–3 caries lesions
1
4–7 caries lesions or no teeth in maxilla or mandible
2
≥ 8 caries lesions or relics or no teeth
3
Caries
Periodontitis
Periapical lesions
4–5 mm deep gingival pocket
1
≥ 6 mm deep gingival pocket
2
Pus in gingival pocket
3
1 periapical lesion or vertical bone pocket or both
1
2 periapical lesions
2
≥ 3 periapical lesions
3
Absent
0
Present
1
Pericoronitis PIBI = Ʃ (Nmod PPD + 2Nadv PPD). Nmod, number of sites with moderate periodontal lesions (4–5 mm). Nadv, number of sites with advanced periodontal lesions (≥ 6 mm).
146 patients
93 other kidney diseases (60 men, 33 women)
53 diabetic nephropathy (38 men, 15 women)
1 periodontal status missing 92 other kidney disease (59 men, 33 women)
1 periodontal status missing 52 diabetic nephropathy (38 men, 14 women)
Total 144 CKD patients (with clinical periodontal status)
Fig 2
Study profile.
paring the diabetic nephropathy group with the other kidney disease group, and patients with lower A1C values (< 6.5%) with higher (≥ 6.5%) A1C values, respectively. The percentages of different variables were compared. A1C values were compared by means between the diabetic nephropathy group and other kidney disease group by independent samples t test as appropriate. Multivariate analyses with covariates sex, age, smoking, PIBI, TDI, and deep periodontal pockets
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(two or more teeth with PPD ≥ 5 mm and two or more sites with ≥ 6 mm) were conducted using binary logistic regression with Wald test regarding the A1C values.
RESULTS Periodontal disease Of the 146 patients, 53 had diabetic nephropathy (30 [20.5%] DM I, 23 [15.8%] DM II), while 93 (63.7%) had
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Table 2
Basic characteristics of the patients
Age (mean ± SD; years)
Diabetic nephropathy, n = 52 (36%)
Other kidney disease, n = 92 (64%)
DM I (30), DM II (22)
CKD total, N = 144 (100%)
P*
55 ± 12.5
52 ± 13.5
54 ± 12.9
.170
Men
59 (64.1%)
38 (73.1%)
97 (67.4%)
Women
33 (35.9%)
14 (26.9%)
47 (32.6%)
Current smoker
22 (31.4%)
11 (32.4%)
33 (31.7%)
Nonsmoker
48 (68.6%)
23 (67.6%)
71 (68.3%)
Sex
.271
Smoking†
.924
A1C (%)‡ (mean ± SD)
5.7 ± 0.8, N = 63
8.2 ± 1.6, N = 52
6.8 ± 1.8
< 6.5% (< 48 mmol/mol)
55 (87.3%)
5 (9.6%)
60 (52.2%)
≥ 6.5% (≥ 48 mmol/mol)
8 (12.7%)
47 (90.4%)
55 (47.8%)
< .001 < .001
*P value (unadjusted) obtained from Pearson χ2 and independent-sample t test (Mann-Whitney test) when comparing mean age and mean A1C (%). †104 smoking status included, exsmokers (n = 32) were excluded, 8 smoking status missing. ‡A1C (%) available from 115 patients.
other CKD, respectively. As shown in Fig 2, periodontal pockets were measured from 144 patients. Only one patient had no specific diagnosis for kidney failure. The other CKD diagnoses included among others polycystic kidney disease (n = 31), nephrosclerosis (n = 16), immunoglobulin A (IgA)-nephropathy (n = 13), focal segmental glomerulosclerosis (n = 9), and membranous glomerulonephritis (n = 4). Mean A1C was 5.7% (± 0.8) in the other CKD group, and 8.2% (± 1.6) in the diabetic nephropathy group (P < .001). Table 2 gives basic characteristics of the patients. No statistically significant differences were found between the background variables other than in the working status.11 In general, the prevalence of periodontal disease (PPD ≥ 4 mm) was high among the CKD patients (88%). This was diagnosed in 90% of the diabetic nephropathy patients and in 87% of the other CKD patients, respectively. This result was not statistically significant, however (Table 3). Comparing the different PPDs, the diabetic nephropathy group had more often two or more teeth with PPD ≥ 5 mm than the other CKD group. This defines moderate periodontitis according to the CDC/ AAP (Table 3). When comparing the different A1C values, however, patients with higher A1C values associated with moderate periodontitis more often (67%) than patients with lower A1C values (40%), respectively (P < .005)
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(Table 4). Of the diabetic nephropathy patients 39% (or patients with higher A1C 36%) had two or more sites with PPD ≥ 6 mm compared with 19% of the other CKD patients (or 18% with lower A1C values), and patients with only 0 to 1 sites with ≥ 6 mm PPD were more common in the other CKD group, and with lower A1C values (82%), than in the diabetic nephropathy group (62%) or with higher A1C values (64%), respectively (P < .05) (Tables 3 and 4). There was no statistically significant difference in the prevalence of furcation lesions between the different subgroups. A Class I furcation lesion was found in 25% of CKD patients, a Class II lesion in 14%, and a Class III lesion in 4% of CKD patients.
Radiographic examination Maximum alveolar bone loss was investigated from each sextant in the panoramic radiographs. In general, alveolar bone loss (vertical or horizontal) was common in the CKD patients. Bone loss up to cervical thirds of root lengths was observed in 54%, while alveolar bone loss up to middle thirds was observed in 31%. Apical thirds of root lengths was found in 12% of the CKD patients (Table 3). There was no statistically significant difference in bone loss when comparing the different CKD diagnoses or when comparing the different A1C values, respectively (Tables 3 and 4).
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Table 3
Periodontal status parameters
Parameter
Other CKD, n = 92 (64%)
Diabetic nephropathy, n = 52 (36%)
CKD total, N = 144 (100%)
P*
Number of teeth, median ± SD
26 ± 8.1
24 ± 7.3
25 ± 7.8
.144
No periodontal pocket/subject
12 (13.0%)
5 (9.6%)
17 (11.8%)
≥ 1 site with ≥ 4 mm PPD
80 (87.0%)
47 (90.4%)
127 (88.2%)
0–1 teeth with ≥ 5 mm deep PPD†
48 (52.2%)
20 (38.5%)
68 (47.2%)
≥ 2 teeth with ≥ 5 mm deep PPD
44 (47.8%)
32 (61.5%)
76 (52.8%)
0–1 site with ≥ 6 mm deep PPD
75 (81.5%)
32 (61.5%)
107 (74.3%)
≥ 2 sites with ≥ 6 mm deep PPD
17 (18.5%)
20 (38.5%)
37 (25.7%)
Yes
46 (54.1%)
23 (54.8%)
69 (54.3%)
No
39 (45.9%)
19 (45.2%)
58 (45.7%)
Yes
25 (29.4%)
14 (33.3%)
39 (30.7%)
No
60 (70.6%)
28 (66.7%)
88 (69.3%)
Yes
9 (10.6%)
6 (14.3%)
15 (11.8%)
No
76 (89.4%)
36 (85.7%)
112 (88.2%)
PIBI (0–5)
50 (54.3%)
23 (44.2%)
73 (50.7%)
PIBI (6–111)
42 (45.7%)
29 (55.8%)
71 (49.3%)
TDI (0–3)§
55 (64.7%)
19 (45.2%)
74 (58.3%)
TDI (4–10)
30 (35.3%)
23 (54.8%)
53 (41.7%)
.540
.113
.008
Cervical Maximum bone loss‡
.945
Middle
.652
Apical
.544
.243
.036 *P value (unadjusted) obtained from Pearson χ2 test and Mann-Whitney when comparing median number of teeth. Bold indicates statistical significance (P < .05). †Moderate periodontitis case definition according to the CDC/AAP. ‡Maximum bone loss of root lengths (horizontal or vertical) in any sextant. §Panoramic radiograph available from 127/144 (17 missing).
PIBI Patients with higher A1C values showed higher PIBI scores (PIBI 6 to 111 in 62%) compared with patients with lower A1C (PIBI 6 to 111 in 40%; P < .05) (Table 4).
pared with the other CKD group (35%) (P < .05) (Table 3). Higher A1C values associated with higher TDI scores (4 to 10 in 51%) when compared with patients with lower A1C values (4 to 10 in 41%), but the result was not statistically significant (Table 4).
Smoking Smokers were divided into two groups, namely current and nonsmokers, while exsmokers were excluded. Smokers had statistically significant higher TDI values (P < .05). No statistically significant difference was observed in the effect of smoking on the subjects with higher A1C, and severity of periodontitis, or high PIBI scores, respectively.
TDI TDI and A1C values were available from only 99 patients. Diabetic nephropathy diagnosis associated more often with higher TDI scores (4 to 10 in 55%) com-
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Multivariate analyses According to multivariate analyses no variable seemed to be significant to A1C values (Table 5).
DISCUSSION The main finding in the present study was that periodontal disease indeed was prevalent in predialysis CKD patients and that high oral infection burden (assessed by using deep PPD, the PIBI, and TDI scorings) was associated with poor metabolic control among these patients. Diabetic nephropathy patients or patients
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Table 4
A1C’s association on number of periodontal pockets, alveolar bone loss, PIBI, and TDI A1C < 6.5% (< 48 mmol/ mol), n = 60 (42%)†
A1C ≥ 6.5% (≥ 48 mmol/ mol), n = 55 (38%)†
Total, N = 115
P*
Number of teeth, median ± SD
25 ± 8.7
24 ± 7.1
25 ± 7.8
.688
No periodontal pockets/subject
7 (11.7%)
5 (9.1%)
12 (10.4%)
≥ 4 mm PPD
53 (88.3%)
50 (90.9%)
103 (89.6%)
0–1 teeth with ≥ 5 mm deep pocket
36 (60.0%)
18 (32.7%)
54 (47.0%)
≥ 2 teeth with ≥ 5 mm deep pockets
24 (40.0%)
37 (67.3%)
61 (53.0%)
0–1 sites with ≥ 6 mm deep pocket
49 (81.7%)
35 (63.6%)
84 (73.0%)
≥ 2 sites with ≥ 6 mm deep pockets
11 (18.3%)
20 (36.4%)
31 (27.0%)
.652
.003
.030 Yes
31 (57.4%)
25 (55.6%)
56 (56.6%)
No
23 (42.6%)
20 (44.4%)
43 (43.4%)
Yes
17 (31.5%)
15 (33.3%)
32 (32.3%)
No
37 (68.5%)
30 (66.7%)
67 (67.7%)
Cervical Maximum bone loss‡
.853
Middle
.844 Yes
6 (11.1%)
7 (15.6%)
13 (13.1%)
No
48 (88.9%)
38 (84.4%)
86 (86.9%)
PIBI (0–5)
36 (60.0%)
21 (38.2%)
57 (49.6%)
PIBI (6–111)
24 (40.0%)
34 (61.8%)
58 (50.4%)
TDI (0–3)§
32 (59.3%)
22 (48.9%)
54 (54.5%)
TDI (4–10)
22 (40.7%)
23 (51.1%)
45 (45.5%)
Apical
.514
.019
.302 *P value (unadjusted) obtained from Pearson χ2 test and Mann-Whitney when comparing median number of teeth. Bold indicates statistical significance (P < .05) †A1C (%) available from 115 patients (29 missing). Panoramic radiograph analysis available from 127/144 (17 missing). ‡Maximum bone loss of root lengths (horizontal or vertical) in any sextant. §Both A1C (%) and panoramic radiograph analysis available from 99 patients (see maximal bone loss and TDI).
Table 5
Variables affecting A1C levels (odds ratios and 95% confidence intervals [CI] based on logistic regression)
Independent variables
A1C values ≥ 6.5%* (n = 33), P†
OR (95% CI)
.789
1.2 (0.4–3.6)
.562
1.4 (0.5–4.0)
.152
0.4 (0.2–1.4)
.216
0.4 (0.1–1.6)
.419
0.6 (0.2–2.0)
.632
0.7 (0.2–2.9)
.615
0.7 (0.2–2.9)
Male Sex Female‡ ≤ 54 y Age, median > 55 y‡ Current smokers Smoking Nonsmokers‡ 0–5 PIBI 6–111‡ 0–3 TDI 4–10‡ 0–1 sites with ≥ 6 mm PPD PPD ≥ 2 sites with ≥ 6 mm PPD‡ 0–1 teeth with ≥ 5 PPD Moderate periodontitis ≥ 2 teeth with ≥ 6 mm PPD‡ *The reference category is 0–6.4. †P value obtained from Wald test. ‡This parameter is set to zero because it is redundant.
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with high A1C values in general showed poorer periodontal health as expected. The results thus confirmed the study hypotheses. The review by Chambrone et al19 concludes that there is enough evidence to support the association between periodontitis and CKD. Earlier studies have also shown an association between poor metabolic control (high A1C values) and suboptimal periodontal treatment outcome.20 Reasons for the association between periodontitis and CKD are explained by uremia with subsequent impaired immune system which results in decreased host response, intense psychologic burden among the patients, hyperparathyroidism, or diabetes.21 In general, there is a well-known two-way relationship between periodontitis and diabetes, and poor periodontal health may exacerbate glycemic control, and vice versa.22,23 This should be taken into account when treating CKD patients. Periodontal treatment as such can improve glycemic control; improvement of A1C level by 0.4% has been subsequently reported.24-26 Periodontitis increases chronic systemic inflammatory burden through pro-inflammatory cytokines and by invasion of bacteria and their products to bloodstream. Periodontal disease could even be considered as a non-traditional risk factor for CKD.27 A study by Kshirsagar et al28 found an association with antibodies to the periodontal pathogens Porphyromonas gingivalis, Treponema denticola, Aggregatibacter actinomycetemcomitans and CKD. In the present study, the focus was the number of periodontal deep pockets, radiologic bone loss, and the number of caries, periapical, and pericoronitis lesions. The limitation of the present retrospective study is that bleeding on probing results, Plaque Index, or CAL values could not be taken into account, since these parameters had not been reported systematically in all patients. Lack of data made it impossible to use the thorough definition for severe (or mild) periodontitis according to CDC/AAP.15 Hence only the definition for moderate periodontitis (two or more teeth with PPD 5 mm or deeper) could be used. The PIBI score reflects the subgingival inflammatory area better than CAL,
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however. A limitation of the study was also that alveolar bone loss was measured only from panoramic radiographs while caries lesions were recorded at clinical examination. However, focused radiographs were taken when needed. Another limitation was that other diseases or drugs used by the patients were not taken into account. These aspects were given in more detail in the previous study by Vesterinen et al.11 A further limitation was that there was no healthy control group in the original study, as well as the slightly small size of the data due to practical reasons. These weaknesses could thus not be avoided due to the nature of the investigation. In the present study a statistically significant difference was found between the different subgroups of CKD and between the different A1C values by comparing deep periodontal pockets, TDI, and PIBI scores, respectively. TDI is the sum of severity of dental diseases and was used for a holistic approach in the measuring of mouth-derived infection burden, not only that of periodontitis. This index was originally used by Mattila et al17 in assessing the link between poor dental health and coronary heart disease. The index has since been well documented. Smoking has been associated with both periodonti29,30 tis and CKD.31 A study by Hallan and Orth32 showed in a Norwegian population that current smokers had 4.0 times higher and former smokers 3.3 times higher risk for kidney failure than never smokers, respectively. In the present study, however, no effect of smoking other than on higher TDI values could be found. Many predialysis patients are potential dialysis patients and prospective kidney transplant recipients. Treating all infections is especially important in patients who will later have an organ transplant with subsequently higher risk of post-transplant complications.8 The future aim is to follow patients through dialysis and up to the kidney transplant phase. Finally, the present study gives, for the first time, information about oral health among predialysis CKD patients. The results could benefit the whole health care cycle of CKD patients especially in hospital units. Hence the present findings may also offer hypothesis generation for further treatment studies.
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CONCLUSION Studies of the association between periodontitis and CKD have mainly investigated patients on maintenance hemodialysis. Findings on predialysis stage patients of different CKD etiology are reported herein. The results showed that diabetic nephropathy patients had more often deep periodontal pockets, and higher TDI scores, compared with the other CKD patients, and that A1C levels ≥ 6.5% (≥ 48 mmol/mol) associated with more severe oral infection burden than lower A1C levels < 6.5% (< 48 mmol/mol). Many of these predialysis patients are potential prospective dialysis patients and kidney transplant recipients. Therefore oral and particularly periodontal infection could be an important source of systemic inflammation and should subsequently be diagnosed and treated on time.
ACKNOWLEDGMENT This study was funded by hospital research funding (EVO TYH20012128), Finnish Women Dentists’ Association, and by the Finnish Dental Society Apollonia.
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