Prevalence of oral infections in chronic kidney disease patients: A cross-sectional study

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Oral Diseases. 2023;00:1–8. wileyonlinelibrary.com/journal/odi

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1 | INTRODUCTION

Chronic kidney disease (CKD) is a progressive, slow, silence, and irre- versible disease characterized by a gradual destruction of the neph- rons and a consequent reduction of kidney function in a few months or years and cause a systemic inflammatory reaction. CKD is clinically defined as estimated decrease glomerular filtration rate (GFR)

<60 mL/min/1.73 m², for 3 months or more (Levey et al., 2005). The

number of patients with CKD is increasing worldwide, estimating its global prevalence, including the end- stage kidney disease, between 11% and 13%, being stage 3 (GFR 30– 59) the most prevalent (7.6%) (Hill et al., 2016). Thus, CKD can be considered a main public health problem (Evans et al., 2022). The well- established risk factors for people with CKD include uncontrolled diabetes, cardiovascular disease, uncontrolled high blood pressure, and age more than 60 years (Stevens et al., 2006). The life- saving treatment of CKD includes DOI: 10.1111/odi.14663

O R I G I N A L A R T I C L E

Prevalence of oral infections in chronic kidney disease patients:

A cross- sectional study

Eduarda Palmeira

¹

| Flor de Liz Pérez- Losada

²

| Víctor Díaz- Flores- García

³

| Juan J. Segura- Sampedro

⁴

| Juan J. Segura- Egea

⁵

| José López- López

²

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

1Hospital Geral de Santo António, Oporto, Portugal

2Department of Odontostomatology, Faculty of Medicine and Health Sciences (School of Dentistry), University of Barcelona, Barcelona, Spain

3Department of Pre- Clinical Dentistry, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain

4General & Digestive Surgery Unit, Hospital Universitario Son Espases, School of Medicine, Health Research Institute of Balearic Islands, University of Balearic Islands, Palma de Mallorca, Spain

5Department of Stomatology, School of Dentistry, University of Seville, Seville, Spain

Correspondence

Juan J. Segura- Egea, Facultad de Odontología, C/ Avicena s/n, Seville 41009, Spain.

Email: [email protected]

José López- López, Department of Odontostomatology, Faculty of Medicine and Health Sciences (School of Dentistry), University of Barcelona, L’Hospitalet de Llobregat, 08907, Barcelona, Spain.

Email: [email protected]

Abstract

Objectives: The purpose of this investigation was to analyze the prevalence of apical periodontitis (AP) and periodontal disease (periodontitis) (PD) in Chronic kidney disease (CKD) patients in relation to their treatment phase.

Subjects and Methods: In this cross- sectional study, 188 patients with CKD were divided into two groups: patients without dialysis (WD group, n = 53) and patients on dialysis (DP group, n = 135). Panoramic radiographs were used to diagnose AP. The presence of periodontal disease was evaluated radiographically assessing alveolar bone loss. Student's t- test, chi- squared test, and logistic regression analysis were used to determine the significance of differences between groups.

Results: In the WD group, 55% of patients had at least one tooth with AP, whereas in the DP group 67% had at least one tooth with AP (OR = 2.11; 95% CI = 1.09– 4.08;

p < 0.05). PD was more prevalent in the DP group (78%) than in the WD group (36%) (OR = 6.26; CI 95% = 3.13– 12.52; p < 0.01).

Conclusions: Oral infections are more prevalent in the advanced stages of CKD. The treatment of PD and AP should be incorporated in the treatment planning of patients with CKD.

K E Y W O R D S

chronic apical periodontitis, chronic kidney disease, dialysis, endodontics, periodontal disease

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dialysis (hemodialysis or peritoneal dialysis), which is the most common treatment, and/or kidney transplant (Bailie et al., 2005).

On the other hand, inflammation is the result of the body's immune response to different stimuli. In acute inflammation, the primary immune response draws immune cells to the site of injury, thus resolving the problem and allowing a return to the status quo.

However, chronic inflammation, the result of acquired immune response, can lead to tissue damage and fibrosis, having been associated with numerous diseases, such as arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, cancer, aging, and CKD (Germolec et al., 2018). Chronic inflammation is considered a risk factor for CKD. In chronic debilitating disorders, such as CKD, systemic persistent inflammation becomes maladaptive, uncontrolled and persistent, being recognized as a major contributor to the uremic phenotype (Cobo et al., 2018).

A high percentage of CKD patients suffer from apical periodontitis (AP) or periodontal disease (periodontitis) (PD), two very similar oral infections that cause chronic oral inflammation (Ruokonen et al., 2019). Both AP and PD are chronic infections of the oral cavity characterized by the inflammation and destruction of the connective tissue and bone around the teeth. Both diseases are polymicrobial infections sharing a common microbiota with a predominance of gram- negative anaerobic bacteria associated with numerous bacte- rial species existent in the oral biofilm of the gingiva and teeth sur- face (Siqueira & Rôças, 2014). Finally, elevated cytokine levels may be released systemically from acute and chronic manifestations of both disease processes (Caplan et al., 2006). Moreover, both AP and PD have been associated with several systemic diseases such as cardiovascular disease, diabetes mellitus, pulmonary disease, obesity, chronic liver disease, and others (Castellanos- Cosano et al., 2013;

Cintra et al., 2021; Kalhan et al., 2022; Segura- Egea et al., 2015;

Segura- Sampedro et al., 2022). In AP and PD, the exacerbated local immune response may reflect systemically, showing mechanisms that are still unknown, but capable of triggering changes that may or not have a systemic repercussion depending on the organism of each in- dividual or even potentiate a systemic condition (Cintra et al., 2021).

Regarding CKD, a significant positive association between PD and CKD has been established (Deschamps- Lenhardt et al., 2019;

Nylund et al., 2018; Ruokonen et al., 2019; Shimizu et al., 2023).

Moreover, PD is universally present in patients undergoing peritoneal dialysis, and the presentation of periodontitis influences their systemic inflammatory state (Chen et al., 2023). On the other hand, a previous study have found association between the prevalence of AP and patients with end- stage renal disease (Khalighinejad et al., 2017). However, no study has investigated the prevalence of AP in CKD patients in different phases of treatment.

The purpose of this investigation was to analyze the prevalence of AP and PD, in CKD patients in relation to their treatment phase.

The primary null hypothesis is that the prevalence of oral infections is the same in predialysis patients as in those undergoing dialysis.

The secondary null hypothesis is that the prevalence of oral infections is the same in peritoneal dialysis patients as in those undergoing hemodialysis.

2 | MATERIALS AND METHODS

2.1 | Patients

Patients were recruited when they went to treatment of CKD or routine consults of nephrology at the Hospital Geral de Santo António, Oporto (Oporto, Portugal). Patients with renal diseases, diagnosed with CKD according with internal protocols of the hospital (KDIGO— Kidney Disease Improving Global Outcomes Guidelines) (Stevens & Levin, 2013). They were asked to voluntary participated and sign the informed consent form, approved by the ethical committee of the Hospital Geral de Santo António of Oporto, Portugal. Only three patients refused to participate. Once the minimum sample size was widely surpassed, the recruitment was terminated.

Questionnaires were filled for each patient and the medical and biochemical parameters were collected from the medical reports of the hospital, including age, gender, smoking status, the diagno- sis of CKD, the stage of CKD, current level of glomerular filtration rate (GRF), and the presence of diabetes or cardiovascular diseases.

Dental information, including periapical status and periodontal status, was obtained directly through a clinical review of each patient.

2.2 | Inclusion and exclusion criteria

The inclusion criteria were patients aged between 18 and 80 years, with history of CKD (GRF < 60 mL/min/1.73m²) and with no change of medication in the last 3 months.

The exclusion criteria were patients under 18 years and older than 80 years, with no history of CKD, with changes in the medication in the last 3 months and patients who did not agree to a radio- logic examination.

A total of 188 patients with CKD, 90 men and 98 women, agreed and were included in the study. The patients were divided into two groups according to the stage of renal failure they suffered: the patients who did not yet need dialysis constituted the WD (without dialysis) group (n = 53), and those who were already on dialysis, ei- ther peritoneal or hemodialysis, were included in the DP (dialysis patients) group (n = 135).

2.3 | Assessment of periapical status

First, observer were calibrated. One investigator examined 30 periapical and panoramic radiographies, following the Orstavik et al. (1986) criteria and using the Periapical Index (PAI) score.

When all the data were analyzed, the investigator participated in a calibration course for the PAI system that consists of two investigators to see 100 periapical radiographic images of the teeth, provided by Dr. Ørstavik. Using the visual references of Ørstavik et al., a PAI score was assigned to each tooth. After each teeth have a PAI score, the results were compered and calculated the Kappa Index.

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The Kappa Index will provide a concordance between the two co- investigators. We obtained a Kappa Index with a value of a K ≥ 0.81, which was a valid value.

Once we obtained a Kappa Index valid, we started analyzing the panoramic radiographies of the descriptive study. The panoramic radiographies of 188 patients were facilitated by the Department of Stomatology and Maxillofacial of the Hospital of Sto. António, Oporto. All the panoramic radiographies were analyzed between 2 p.m. and 6 p.m. and with environmental light. The periapical status was assessed using the PAI score (Orstavik et al., 1986), as described previously (López- López et al., 2012; Segura- Egea et al., 2011). A score >2 (PAI ≥ 3) was considered to be a sign of periapical pathology. The worst score of all roots was taken to rep- resent the PAI score for multirooted teeth. Teeth were categorized as root- filled teeth if they had been filled with a radiopaque mate- rial in the root canal(s).

2.4 | Assessment of periodontal status

The presence of periodontal disease was evaluated radiographically assessing alveolar bone loss. The height of the alveolar bone crest was measured from a fixed reference point (the cementoenamel junction) proximal to all available teeth. Subjects with alveolar bone loss ≥4 mm were considered periodontal patients (Oettinger- Barak et al., 2007).

2.5 | Description of the variables

The successive variables were drawn from the patient's medical history and from the panoramic radiographies: sex (qualitative variable);

age (quantitative variable); number of teeth (quantitative variable);

type of CKD (qualitative variable), according of the data provided by the department of Nephrology of the Hospital Sto. António and according the classification of KDIGO; smoking habits (dichotomized qualitative variable); presence of diabetes mellitus (dichotomized qualitative variable); periodontal disease (dichotomized qualitative variable); periapical status (dichotomized qualitative variable), number of teeth with apical periodontitis (quantitative variable); and number of root- filled teeth (RFT) (quantitative variable).

2.6 | Statistical analysis

The minimal sample size (n = 121) was calculated using the sample size calculator software of the National Center for Advancing Translational Sciences (NIH, UK), (NIH, n.d.) for the comparison of proportions in two independent samples, with continuity correction.

They were taken into account a two- sided significance level of 5%

(α = 0.05, Zα = 1.960), and 80% power (β = 0.20, Zβ = 0.842). The calculations were performed in order to detect a twofold difference in risk. Thus, the baseline risk was established in 0.3 in WD group,

and the risk in DP was established in 0.6. Raw data were entered into Excel (Microsoft Corporation). All analyses were done in an SPSS environment (Version 11; SPSS, Inc). The Student's t- test, chi- squared test, and logistic regression analysis were used to determine the significance of differences between groups. Data are reported as mean ± standard deviation. According to the established significance level, a value of p ≤ 0.05 was considered statistically significant.

2.7 | Ethical standards

This study was guide the accord of the ethical principles of the Helsinki Declaration and the study had the approval of the Ethics Committee of the Hospital Sto. António de Oporto, Portugal (number 132/10. 085- Departamento de Ensino, Formaçao e Investigaçao/125- CES).

Personal data and the name of the patients in all the study were always kept anonymous, and also did not appear in any document during the study or in any publication or communication made in the study. The panoramic radiographies were moved every time in an anonymous way.

The study was made according to the General Rules of Data protection (EU) 2016/679 Appl. Sci. 2022, 12, 7141 6 of 15 and the Organic Law 3/2018, 5th December, of Data Personal Protection and Digital Rights Guarantee.

3 | RESULTS

The distribution of analyzed variables among patients with CKD is shown in Table 1. The proportion of men and women in both groups was similar (p > 0.05). On the contrary, mean age of patients in the WD group was aged 42.6 ± 13.6 years old, whereas in the DP group mean age of patients was higher (54.2 ± 12.4 years old; p < 0.01). The average number of teeth per patient was 25.5 ± 3.2 and 23.5 ± 4.3 teeth in the WD and DP groups, respectively (p < 0.01).

Regarding the periapical status, in the WD group, the average number of teeth with AP was 1.0 ± 2.0, whereas in the DP group, it was 5.2 ± 5.3 (p < 0.01). Taking the patient as a reference, in the WD group 29 patients (54.7%) had at least one tooth with radiolucent periapical lesion (RPL), whereas in the DP group 97 patients (67.4%) had at least one tooth with RPL. The calculated odds ratio (OR) was 2.11 (CI 95% = 1.09– 4.08; p < 0.05). The number of RFT was similar in both groups, being 1.6 ± 1.7 in the WD and 1.7 ± 2.3 in the DP (p > 0.05).

Periodontal disease was more prevalent in the DP group (77.8%) than in WD patients (35.8%) (OR = 6.26; CI 95% = 3.13– 12.52;

p < 0.01). There were no significant differences in smoking between both groups (p > 0.05). On the contrary, the percentage of diabetic patients was higher in the DP group (42.2%) compared to the WD group (17.0%) (OR = 3.57; CI 95% = 1.61– 7.90; p < 0.01).

To analyze which variables were associated to CKD (dependent variable), multivariate logistic regression analyses were run with age,

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gender, number of teeth, number of RFT, diabetic status, smoking habits, periodontal status, and periapical status (number of teeth with apical periodontitis) as independent variables (Table 2). In the multivariate analysis, including all the above factors as covariates, periodontal status was associated to the treatment stage of CKD (OR = 3.29; CI 95% = 1.40– 7.75; p = 0.0065).

To better investigate the possible relationship between inflammatory oral diseases and the type of dialysis treatment, the distribution of analyzed variables among patients with peritoneal dialysis and patients undergoing hemodialysis is shown in Table 3. The proportion of men and women in both groups was similar (p > 0.05). On the contrary, mean age of patients on hemodialysis was almost 10 years higher than that of patients on peritoneal dialysis (p < 0.0001). The average number of teeth per patient was similar in both group of patients (p > 0.05).

Concerning the periapical status, the average number of teeth with AP was 3.4 ± 4.2 in peritoneal dialysis patients, whereas in hemodialysis patients, it was 5.8 ± 5.6 (p < 0.01). Taking the patient as a reference, in peritoneal hemodialysis patients (63.5%) had at least one tooth with radiolucent periapical lesion (RPL), whereas in patients on hemodialysis (79.2%) had at least one tooth with RPL. The WD (n = 53) DP (n = 135)

Total

(n = 188) p Value/OR Age/Years, Mean ± SD 42.6 ± 13.6 54.2 ± 12.4 50.9 ± 13.7 <0.01 Gender (n, %)

Male 24 (45.3) 66 (48.9) 90 (47.9) >0.05

Female 29 (54.7) 69 (51.1) 98 (52.1)

No. teeth, Mean ± SD 25.5 ± 3.2 23.5 ± 4.5 24.1 ± 4.3 <0.01 No. teeth with AP,

Mean ± SD

1.0 ± 2.0 5.2 ± 5.3 4.0 ± 4.9 <0.01

Teeth with AP

Present 29 (54.7) 97 (67.4) 126 (67.0) <0.05

Absent 24 (45.3) 38 (32.6) 62 (33.0)

OR (95% CI) 2.11 (1.09– 4.08)

No. of RFT, Mean ± SD 1.6 ± 1.7 1.7 ± 2.3 1.7 ± 2.1 >0.05 Periodontal status

Present 19 (35.8) 105 (77.8) 124 (66.0) <0.01

Absent 34 (64.2) 30 (22.2) 64 (34.0)

OR (95% CI) 6.26 (3.13– 12.52)

Diabetes

Present 9 (17.0) 57 (42.2) 66 (35.1) <0.01

Absent 44 (83.0) 78 (57.8) 122 (64.9)

OR (95% CI) 3.57 (1.61– 7.90)

Smoking habits

Present 18 (34.0) 32 (23.7) 50 (26.6) >0.05

Absent 35 (66.0) 103 (76.3) 138 (73.4)

OR (95% CI) 0.60 (0.30– 1.21)

Note: OR values, and their 95% CI, have been estimated using chi- squared test.

Abbreviations: CI, confidence interval; CKD, Chronic kidney disease; DP group, dialysis patients group; OR, Odds ratio; WD group, without dialysis group.

variables among patients with CKD.

TA B L E 2 Multivariate logistic regression analyses of the influence of the independent variables age, gender (0 = female;

1 = male), number of teeth, number of RFT, diabetic status (0 = absent; 1 = present), smoking habits (0 = absent; 1 = present), periodontal status (0 = absent; 1 = present), and periapical

status (number of teeth with apical periodontitis), on the dependent variable “treatment stage of CKD” (0 = predialysis; 1 = dialysis).

Independent variable p Odds

ratio 95% CI

Inf. limit 95% CI Sup. limit

Age 0.0091 1.0510 1.0124 1.0910

Gender 0.5575 1.2660 0.5757 2.7840

No teeth 0.6180 0.9683 0.8532 1.0990

No RFT 0.2730 0.9078 0.7635 1.0793

Diabetes 0.7816 1.1565 0.4137 3.2325

Smoking habit 0.0203 0.3547 0.1479 0.8510

Periodontal status 0.0065 3.2886 1.3959 7.7477 Periapical status 0.4500 1.0359 0.9453 1.1351 Note: Overall model fit: χ² = 46.1289; df = 8; p = 0.0000.

Abbreviations: AP, apical periodontitis; CKD: chronic kidney disease;

RFT, root filled teeth

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calculated odds ratio (OR) was 2.19 (CI 95% = 1.02– 4.70; p < 0.05).

The number of RFT was similar in both groups of dialysis treatment (p > 0.05).

Regarding periodontal status, periodontal disease was more prevalent in patients on hemodialysis (91.7%) than in peritoneal dialysis patients (61.9%) (OR = 6.77; CI 95% = 2.54– 18.00; p < 0.01). The group of hemodialysis patients showed significantly higher percent- ages of both smokers (OR = 3.44; CI 95% = 1.417– 6.81; p < 0.01) and diabetics (OR = 4.48; CI 95% = 2.13– 9.44; p < 0.01).

To analyze which variables were associated to the type of dialysis treatment (dependent variable), multivariate logistic regression analyses were run with age, gender, number of teeth, number of RFT, diabetic status, smoking habits, periodontal status, and periapical status (number of teeth with apical periodontitis) as independent variables (Table 4). In the multivariate analysis, including all the above factors as covariates, neither periodontal status (OR = 1.94; CI 95% = 0.59–

6.35; p > 0.05) nor periapical status (OR = 1.07; CI 95% = 0.98–

1.17; p > 0.05) were associated with the type of dialysis treatment.

However, smoking status were significantly more prevalent in hemodialysis patients (OR = 4.05; CI 95% = 1.30– 12.60; p < 0.05).

4 | DISCUSSION

In the present study, the prevalence of AP and PD in CKD patients in different phases of treatment have been analyzed. The null hypothesis, that is, the prevalence of AP and PD is the same in predialysis patients and in those undergoing dialysis, must be rejected. CKD patients on dialysis showed significantly higher prevalence of both oral infectious diseases, AP and PD. Patients on peritoneal dialysis and hemodialysis showed similar prevalence of both PD and AP.

The recruitment method of the patients was similar to that used in previous studies (López- López et al., 2011; Piras et al., 2017;

Sánchez- Domínguez et al., 2015). It is possible that CKD patients in dialysis had more concerns about their overall dental health and were more likely to participate in the study. This could result in a spurious association between CKD and periapical or periodontal disease. However, this possibility is unlikely as only three patients refused to participate in the study.

Chronic kidney disease was diagnosed according to the current criteria (Stevens & Levin, 2013). The PAI scoring system have been TA B L E 3 Distribution of analysed variables among patients with

CKD in the DP group, according to the type of dialysis.

PD (n = 63) HD (n = 72) p Value/OR Age/Years,

Mean ± SD 48.2 ± 10.3 59.4 ± 11.7 <0.0001 Gender (n, %)

Male 29 (46.0) 37 (51.4) >0.05

Female 34 (54.0) 35 (48.6)

No. teeth, Mean ± SD 24.3 ± 3.5 22.8 ± 5.2 >0.05 No. teeth with AP,

Mean ± SD 3.4 ± 4.2 5.8 ± 5.6 <0.01 Teeth with AP

Present 40 (63.5) 57 (79.2) <0.05

Absent 23 (36.5) 15 (20.8)

OR (95% CI) 2.19 (1.02– 4.70)

No. of RFT, Mean ± SD

1.9 ± 2.3 1.5 ± 2.2 >0.05

Periodontal status

Present 39 (61.9) 66 (91.7) <0.01

Absent 24 (38.1) 6 (8.3)

OR (95% CI) 6.77 (2.54– 18.00)

Diabetes

Present 15 (23.8) 42 (58.3) <0.01

Absent 48 (76.2) 30 (41.7)

OR (95% CI) 4.48 (2.13– 9.44)

Smoking habits

Present 8 (12.7) 24 (33.3) <0.01

Absent 55 (87.3) 48 (66.7)

OR (95% CI) 3.44 (1.41– 6.81)

Note: OR values, and their 95% CI, have been estimated using chi- squared test.

Abbreviations: CI, confidence interval; HD, hemodialysis; OR, Odds ratio; PD, peritoneal dialysis.

Independent variable p OR 95% CI Inf.

limit 95% CI

Sup. limit

Age 0.0019 1.0792 1.0286 1.1323

Gender 0.2533 0.5801 0.2280 1.4764

No teeth 0.7631 0.9833 0.8812 1.0972

No RFT 0.0995 0.8627 0.7236 1.0285

Diabetes 0.6295 1.2783 0.4714 3.4663

Smoking habit 0.0157 4.0504 1.3022 12.5986

Periodontal status 0.2739 1.9398 0.5919 6.3578

Periapical status 0.1119 1.0719 0.9840 1.1676

Note: Overall model fit: χ² = 44.7484; df = 8; p = 0.0000.

Abbreviations: AP, apical periodontitis; CI, confidence interval; OR, Odds ratio; RFT, root filled teeth.

TA B L E 4 Multivariate logistic regression analyses of the influence of the independent variables age, gender (0 = female; 1 = male), number of teeth, number of RFT, diabetic status (0 = absent;

1 = present), smoking habits (0 = absent;

1 = present), periodontal status (0 = absent; 1 = present), and periapical status (0 = number of teeth with apical periodontitis), on the dependent variable

“type of dialysis” (0 = peritoneal dialysis;

1 = hemodialysis).

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used to assess the periapical status (Orstavik et al., 1986). PAI has been widely used in epidemiological and clinical studies (Kirkevang et al., 2017). Panoramic radiography has the advantages over periapical radiographs of showing all teeth, reducing the patient's ex- posure to ionizing radiation, faster acquisition, and convenience (Gulsahi et al., 2008; Ríos- Santos et al., 2010). Although panoramic radiographs have shown good diagnostic accuracy and high specific- ity in assessing AP, the use of panoramic radiographs has been cor- related with an underestimation of the number of periapical lesions (Eriksen & Bjertness, 1991; Ríos- Santos et al., 2010).

The criteria used to assess periodontal disease (Oettinger- Barak et al., 2007) have also been used previously by other authors (Poyato- Borrego et al., 2023). As it is a cross- sectional study, it can- not be taken into consideration if any of the patients had previously undergone periodontal treatment, which could have altered the assessment of their periodontal condition. This is an unavoidable lim- itation of the present study.

The results of the present study have demonstrated that the average number of teeth with AP is almost five- fold in patients in dialysis compared with predialysis patients (p < 0.01). Moreover, the proba- bility of having at least one tooth with AP was double in dialysis patients compared to predialysis patients (OR = 2.11; p < 0.05). Several studies have shown that uremic patients have higher rates of decayed, missing, and filled teeth (Akar et al., 2011). Furthermore, a previously published study showed higher prevalence of teeth with AP in end- stage renal disease patients (OR = 2.6; p < 0.05) compared to control healthy patients (Khalighinejad et al., 2017), but this study did not look at the different phases of CKD. The strikingly finding of the present study that dialysis patients present five times more teeth with AP than predialysis patients is in agreement with the result of the study by Khalighinejad et al. (2017) who found a significant direct association between the number of teeth with AP and urea serum levels.

Regarding PD, dialysis patients showed a prevalence six times higher than predialysis patients (OR = 6.26; p < 0.01), being periodontal status associated to the treatment stage of CKD (OR = 3.29;

p = 0.0065). Other previously published studies have also found a strong association between PD and CKD (Kshirsagar et al., 2005;

Niedzielska et al., 2014). A cross- sectional study comparing patients with different renal diseases undergoing hemodialysis and healthy controls showed much higher poor oral hygiene and PD in dialysis patients compared to the control group (Munagala et al., 2022).

Higher scores of Community Periodontal Index of Treatment Needs index (CPITN) have been associated with more severe stages of CKD (Borawski et al., 2007; Valenzuela- Narváez et al., 2021).

The results of this study indicate that there may be an influence of both oral infections, AP and PD, on CKD. Low- grade inflammation (LGI), a feature common to AP and PD, could also explain this association. LGI is a systemic status of chronic subclinical production of inflammatory factors. This condition represents a risk factor for many chronic diseases including diabetes, cardiovascular disease, cerebrovascular disease, neurodegenerative disease and cancer (Cecoro et al., 2020). Persistent LGI is also a common feature of CKD already before the start of renal replacement therapy, and evidence

suggests that persistent inflammation may also be per se a risk factor for progression of CKD (Yilmaz et al., 2007). Persistent LGI is considered a hallmark feature of CKD, being involved in the development of all- cause mortality of these patients (Mihai et al., 2018).

Well, indeed, both AP and PD are associated with LGI. An increased local release of pro- inflammatory cytokines has been found in periapical lesions of endodontic origin (Bakhsh et al., 2022; Braz- Silva et al., 2019; Georgiou et al., 2023). Moreover, both symptom- atic and asymptomatic AP can contribute to increased systemic levels of molecular markers of inflammation (Bakhsh et al., 2022).

A recently published case– control prospective study has showed that the immunologic profile of chronic AP reveals a systemic LGI through compensatory immunosuppression (Georgiou et al., 2023).

As far as PD is concerned, it is also associated with LGI (Cecoro et al., 2020). CPITN in LGI patients indicated a high severity of periodontitis in all renal failure patients as compared with general population subjects (Borawski et al., 2007). Periodontitis patients have elevated markers of systemic inflammation, such C- reactive protein (CRP), interleukin 6 (IL- 6), haptoglobin, and fibrinogen levels (Andreu et al., 2021; Moutsopoulos & Madianos, 2006).

Both AP and PD, due to its nature of infective inflammatory disease, involves the activation of the broad axis of innate immunity caused by the pathogenic action of subgingival microbiota through upregulation of pro- inflammatory cytokines from monocytes and polymorphonuclear leucocytes, including IL- 1, IL- 6, IL- 8, TNF- α, and PGE2 (Cecoro et al., 2020). It has been suggested that periodontal and periapical inflammation could be an important source of systemic inflammation, partially responsible for the progression of CKD and a burden of atherosclerotic complications in dialysis patients (Niedzielska et al., 2014).

The results of this study should be translated to the clinic. The control of oral health and, especially, the treatment of PD and AP, must be integrated into the follow- up protocol for chronic kidney patients. The results of this study, together with those previously published, should alert clinicians, as well as patients, to the importance of good oral health for the control of renal function. Prophylaxis and early dental treatment should be intensified in CKD patients (Borawski et al., 2007). The treatment of PD and AP should be incorporated in the treatment planning of patients with CKD.

5 | CONCLUSIONS

The present results demonstrate that oral infections are more prevalent in the advanced stages of CKD. Considering that PD is prevalent, severe and under recognized in renal failure patients, and the higher number of teeth with AP in dialysis patients demonstrated in the present study, the treatment of PD and AP should be incorporated in the treatment planning of patients with CKD.

AUTHOR CONTRIBUTIONS

Eduarda Palmeira: Investigation; data curation; methodology. Flor de Liz Pérez- Losada: Investigation; methodology; data curation;

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writing – original draft. Víctor Díaz- Flores- García: Investigation;

data curation; visualization. Juan J. Segura- Sampedro: Investigation;

data curation; formal analysis. Juan J. Segura- Egea: Writing – original draft; conceptualization; methodology; writing – review and editing; supervision. José López- López: Conceptualization; writing – original draft; methodology; writing – review and editing; supervision; data curation; project administration.

ACKNOWLEDGMENTS None.

CONFLIC T OF INTEREST STATEMENT All authors have no conflicts of interest to disclose.

DATA AVAIL ABILIT Y STATEMENT

The authors make the study data available on request.

PATIENT CONSENT STATEMENT

The patients were asked to voluntary participated and sign the informed consent form, approved by the ethical committee.

ORCID

Víctor Díaz- Flores- García https://orcid.

org/0000-0001-6141-0546

Juan J. Segura- Egea https://orcid.org/0000-0002-0427-9059 José López- López https://orcid.org/0000-0001-8035-4412

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How to cite this article: Palmeira, E., de Liz Pérez- Losada, F., Díaz- Flores- García, V., Segura- Sampedro, J. J., Segura- Egea, J. J., & López- López, J. (2023). Prevalence of oral infections in chronic kidney disease patients: A cross- sectional study. Oral Diseases, 00, 1–8. https://doi.org/10.1111/odi.14663