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BMC Oral Health
BMC Oral Health
BMC Oral Health
1472-6831
BioMed Central London

39261859
4826
10.1186/s12903-024-04826-1
Research
Exploring the correlation between periodontal disease and serum biomarkers in haemodialysis patients
Basha Maimona Mansour 12
Al-Kadasi Baleegh Abdulraoof perio.bak@gmail.com

2
Al-Hajri Manal 3
Al-Sharani Hesham Mohammed 4
http://orcid.org/0000-0002-6906-8279
Elayah Sadam Ahmed s.elayah90@gmail.com

5
1 https://ror.org/04hcvaf32 grid.412413.1 0000 0001 2299 4112 Periodontology Department, Faculty of Dentistry, Sana’a University, Sana’a, Yemen
2 https://ror.org/00fhcxc56 grid.444909.4 Department of Periodontology and Oral Medicine, Faculty of Dentistry, Ibb University, Ibb, Yemen
3 https://ror.org/04hcvaf32 grid.412413.1 0000 0001 2299 4112 Oral Medicine, Oral Diagnosis, Periodontology, and Oral Radiology Department, Faculty of Dentistry, Sana’a University, Sana’a, Yemen
4 https://ror.org/03fy7b149 0000 0000 9917 4633 National Center for Epidemiology and Population Health, ANU College of Health and Medicine, ACT, Canberra, Australia
5 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Jiblah University for Medical and Health Sciences, Ibb, Yemen
11 9 2024
11 9 2024
2024
24 10664 8 2023
28 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Patients undergoing haemodialysis are more susceptible to infectious diseases, including periodontitis. This study aimed to investigate the Correlation between periodontal disease and serum markers in Yemeni haemodialysis patients.

Methods

A cross-sectional study was conducted on a sample of 70 haemodialysis patients. Patient interviews, clinical examinations, and laboratory tests were performed to collect data. Serum levels of albumin, calcium, phosphorus, haemoglobin, ferritin, and creatinine were measured, with separate measurements for cystatin C The association between categorical variables was assessed using the chi-square test and Pearson’s correlation coefficient, considering a significance level of p < 0.05.

Results

Significant correlations were found between serum biomarkers and periodontal clinical parameters. Phosphorus, creatinine, albumin, ferritin, and creatinine levels correlated significantly with the Plaque Index (p < 0.001, p < 0.001, p = 0.015, p = 0.018, and p = 0.03). While the Ferritin level showed significant correlations with both the Plaque Index and Miller Classes (r = 0.281, p = 0.018 and r = 0.258, p = 0.031), respectively. The Calcium level showed a significant correlation with the Gingival Index (r = 0.266, p = 0.027). Cystatin C level was statistically correlated with mobility (r = 0.258, p = 0.031). Also, the result showed a significant correlation between Creatinine levels and Periodontitis (r = 0.26, p = 0.03).

Conclusion

This study provides evidence of a strong association between periodontal disease and chronic kidney disease in Yemeni haemodialysis patients. The findings emphasize the significance of maintaining good oral health in the care of haemodialysis patients.

Keywords

Periodontal diseases
Haemodialysis
Chronic kidney diseases
Systemic biomarkers
issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
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pmcIntroduction

Chronic kidney disease (CKD) is a prevalent and serious health condition characterized by a progressive loss of renal function, leading to toxin and excess water accumulation that necessitates renal replacement therapy [1, 2]. The primary causes of CKD and subsequent end-stage renal disease (ESRD) are often attributed to diabetes mellitus and hypertension [3]. Chronic and progressive nephropathies contribute to the development of kidney fibrosis and the disruption of the kidney’s normal architecture, resulting in histopathological manifestations such as glomerulosclerosis, tubulointerstitial fibrosis, and vascular sclerosis [4]. There are five types of chronic kidney diseases, the most severe type known as ESRD. It is characterized by decreased renal function leading to toxin and excess water accumulation, with dialysis serving as the primary treatment for ESRD to remove toxins from the body [5].

Periodontitis (PD) is an inflammatory disease that affects the hard and soft tissues surrounding the teeth, and results in the breakdown of the periodontal ligament, alveolar bone, and eventual tooth loss [6]. It is primarily caused by specific microorganisms, mostly gram-negative species, within the dental plaque biofilm [7]. The inflammatory response associated with PD is characterized by low-grade chronic inflammation and has been correlated with systemic consequences, as indicated by elevated levels of inflammatory biomarkers such as serum C-reactive protein [8, 9]. Enhancement in periodontal health will result in lower levels of inflammatory biomarkers [10].

Untreated PD acts as a persistent source of infection and has been linked to the development and progression of various systemic conditions, including cardiovascular, cerebrovascular, and respiratory diseases. [11] Additionally, chronic inflammation has emerged as a risk factor for CKD [12, 13]. Patients who are receiving haemodialysis are more susceptible to infection-related morbidity and mortality due to their compromised immune responses and the potential masking of infection symptoms caused by medication [14, 15]. Consequently, they often exhibit a high prevalence and severity of periodontal disease, which may be present even before the initiation of haemodialysis [16].

Conversely, systemic disorders such as renal failure can exacerbate PD by interfering with the body’s immunological response to periodontal microorganisms, impairing collagen synthesis, and promoting inflammation [17]. This suggests a bidirectional relationship between periodontitis and systemic diseases, indicating the interconnectedness of oral health and overall systemic well-being [18].

In 2018, Afroozi et al. reported that approximately 78% of hemodialysis patients exhibited oral manifestations such as mouth dryness and tooth loss, attributed to tooth mobility and poor oral hygiene. The study also emphasized the significant presence of oral lesions in hemodialysis patients, underscoring the potential for untreated lesions to lead to severe side effects [19]. In 2019, a systematic review and meta-analysis [20], investigated the connection between PD and CKD. The findings revealed that most identified studies pointed to an increased incidence of PD in patients with CKD. Subsequently, in 2020, Dannewitz et al. [21]. examined the prevalence and severity of PD in CKD patients, comparing the results with the self-reported awareness of periodontitis among study subjects. The study highlighted an elevated prevalence of PD in CKD patients, coupled with a low level of self‐reported periodontitis awareness. A descriptive cross-sectional study focusing on the referral of CKD patients to a teaching hospital concluded that regular biannual dental visits are crucial for CKD patients [22].

Despite the importance of understanding the association between periodontal disease and systemic markers in patients receiving haemodialysis, there are limited studies related to this topic [14, 23]. Furthermore, awareness among healthcare professionals, including physicians and dentists, regarding this relationship remains low, particularly in Yemen where no previous studies have been published. Therefore, this study aims to investigate the association between periodontal disease status and serum biomarkers in Yemeni patients who received haemodialysis by evaluating various serum markers alongside periodontal clinical parameters.

Materials and methods

Subjects

A cross-sectional study was conducted on 70 patients (48.6% Male and 51.4% Female) who received haemodialysis for a minimum of six months at the haemodialysis unit of Al-Thawra Republic Hospital in Ibb city, Yemen. Patients with thyroid disorders, tumors, Alzheimer’s disease, viral hepatitis, diabetes mellitus, rheumatoid arthritis, a history of taking bisphosphonates, steroids, or contraceptives, and pregnant or nursing women were excluded from the study [24–26].

The study protocol, which was ethically approved from the Ethical Committee of Medical Research at Sana’a University, has been conducted in accordance to the guidelines of the declaration of Helsinki. Written informed consent was obtained from all patients.

Sample size calculation

The G*power 3.0.10 software was used to calculate the sample size. The minimum sample size required was 65 subjects. This showed that to detect a statistical difference between the groups with a 0.05 target significance value, a sample size of 70 participants and 85% power would be required. In addition, it was conducted based on previous comparable studies [27, 28].

Data collection

The data were collected through a combination of clinical examination and laboratory tests.

Clinical examination

The clinical examinations were conducted with patients in a supine position on haemodialysis beds, exposed to natural sunlight. It was included both extra-oral and intraoral examinations, which performed with a highly experienced specialist. Dental instruments used for periodontal examination, include UNC-15 periodontal probes [29], dental mirrors, dental explorers, cheek retractors cotton rolls, and gauze.

The periodontal examination involved assessing periodontal and gingival indices, encompassing measurements of plaque index (PI), periodontal pocket depth (PPD), bleeding on probing (BOP), gingival index (GI), as well as evaluations of clinical attachment loss (CAL), recession by millimetres, Miller’s classification of recession, and tooth mobility. Based on the Silness and Loe index, The PI was taken by measurements of buccal, lingual, mesial, and distal sites of each tooth, resulting in a score ranging from 0 to 3 [30]. Also, Loe and Silness GI index was used to measure the degree of gingival inflammation including scores ranging from 0 to 3 [31]. The BOP index represented the presence or absence of bleeding on probing, calculated as a percentage. Gingival recession was measured in millimetres from the cementoenamel junction to the gingival margin, with classification based on Miller’s classification [32]. PPD was represented the depth to which the periodontal probe penetrated the periodontal pocket, was obtained at six sites around each tooth. CAL was calculated from recession and PPD measurements [33]. Any visible tooth mobility was classified according to Miller’s classification. [34]

Laboratory tests

The time interval between the clinical examination of patients and their blood tests was kept within two days. Before the application of haemodialysis, blood samples were drawn. To prevent coagulation, the tube containing EDTA in the required concentration was used to conduct a complete blood count (CBC) test, including haemoglobin measurements. A multifunctional mixer device facilitated optimal mixing of the blood sample and EDTA. For the calcium (Ca) test, ferritin measurements, spectrophotometer devices, specifically a semi-auto Chemistry Analyzer were employed after the addition of the appropriate solutions. Conversely, albumin, creatinine, and phosphorus analysis were carried out using the automated device Cobas c 311 Analyzer. To measure Cystatin C levels, blood samples were drawn and promptly processed at the laboratory where blood serum was separated and frozen at -20 °C. The samples, mixed with a specific solution from special tubes using the identity card, were then analysed using an MD-PACIFIC device in the designated laboratory. Ultimately, the serum levels of Cystatin C were measured using a Cystatin C (Cys C) Kit (version: M341709E).

The subsequent analysis of the blood samples was performed utilizing automated and standardized methods, which ensured precision, reproducibility, and the generation of dependable results.

Statistical analysis

This statistical analysis was performed using SPSS version 22(Chicago, USA). T-test was used to analyse the descriptive data. The association between categorical variables was assessed using the chi-square test and Pearson’s correlation coefficient. P < 0.05 was considered statistically significant.

Results

The study consisted of a total of 70 patients (48.6% Male and 51.4% Female), aged range between 20 and 40 years.

Clinical examination outcomes

Every patient was diagnosed with periodontitis, accounting for 100% of the cases. As for oral hygiene habits, 70% practiced habits like tooth brushing or using Miswak, but it was noted that the frequency was irregular in all cases, less than three times per week. Despite all patients suffering from renal failure, there was still a subset who engaged in health-compromising behaviours: 5.7% were smokers, 12.9% chewed khat, and 1.4% used Shamma. Majority of the patients (88.6%) were found to have hypertension, which was identified as the primary cause of their renal failure (Table 1). The mean values and standard deviations of periodontal clinical parameters; PI, GI, GR, PPD, CLA, and mobility were 1.257 ± 0.660, 1.039 ± 0.609, 3.200 ± 1.303 mm, 3.586 ± 0.985 mm, 6.071 ± 1.836 mm, and 0.957 ± 0.770, respectively (Table 2).

Table 1 Distribution of gender, Age, Health behaviours, and diagnosis among study participants

Variable	Category/
Response	Frequency	Percentage (%)	
Gender	Male	34	48.6	
Female	36	51.4	
Age	< 20 yrs.	1	1.4	
20–40 yrs.	41	58.6	
> 20 yrs.	28	40.0	
Smoking	No	66	94.3%	
Yes	4	5.7%	
Khat chewing	No	61	87.1%	
Yes	9	12.9%	
Shamma User	No	69	69.6%	
Yes	1	1.4%	
Oral Hygiene	No	21	30%	
Yes	49	70%	
Teeth mobility	No	22	31.4%	
Yes	48	68.6%	
Hypertension	No	8	11.4%	
Yes	62	88.6%	
Diagnosis	Healthy	0	0%	
Gingivitis	0	0%	
periodontitis	70	100%	

Table 2 Descriptive statistics of periodontal clinical parameters

variables	Mean ± SD	
Plaque index	1.26 ± 0.66	
Gingival index	1.04 ± 0.61	
Gingival Recession	3.21 ± 1.31 mm	
Pocket depth	3.59 ± 0.99 mm	
Clinical Attachment Loss	6.08 ± 1.84 mm	
Mobility	0.96 ± 0.78	
SD, standard deviation; mm, millimetre

Table 3 The association between serum biomarkers and periodontal parameters in Haemodialysis patients

Variable	Biomarkers	serum albumin	Ca	PH	Ferritin	H.B	Creatinine	Cystatin C	
Association	
Plaque index	Correlation	− 0.289*	− 0.220	0.442**	− 0.281*	− 0.278*	0.394**	0.172	
P value	0.015	0.067	0.000	0.018	0.020	0.001	0.154	
Gingival index	Correlation	− 0.072	− 0.266*	0.207	− 0.165	− 0.088	0.187	− 0.142	
P value	0.556	0.027	0.087	0.176	0.473	0.125	0.246	
Gingival Recession	Correlation	− 0.125	− 0.091	− 0.145	0.046	0.142	− 0.061	− 0.032	
P value	0.303	0.454	0.231	0.704	0.240	0.618	0.792	
Miller Class	Correlation	− 0.025	− 0.159	− 0.146	− 0.258*	− 0.166	− 0.075	0.030	
P value	0.840	0.189	0.227	0.031	0.170	0.536	0.806	
Pocket depth	Correlation	− 0.128	− 0.158	0.206	0.005	− 0.146	0.136	0.008	
P value	0.292	0.190	0.087	0.969	0.227	0.261	0.947	
Clinical Attachment Loss	Correlation	− 0.025	− 0.075	− 0.173	0.085	0.097	− 0.065	− 0.174	
P value	0.835	0.540	0.153	0.485	0.423	0.594	0.149	
Mobility	Correlation	− 0.006	0.002	0.117	− 0.088	− 0.059	0.100	− 0.258*	
P value	0.964	0.987	0.336	0.471	0.629	0.412	0.031	

Table 4 The correlation of serum markers in Haemodialysis patients with periodontitis

Variables	Mean ± SD	r	P-value	
Serum albumin	4.26 ± 0.70 g/dl	-0.15	0.21	
Calcium	8.11 ± 0.47 mg/dl	-0.13	0.29	
Phosphorus	6.57 ± 8.04 mg/dl	0.09	0.48	
Haemoglobin	9.27 ± 1.89 g/d	0.04	0.78	
Ferritin	521.04 ± 450.54 ng/ml	0.13	0.30	
Creatinine	7.90 ± 2.46 mg/dl	0.26*	0.03	
Cystatin C	2.11 ± 2.92 mg/l	0.09	0.46	
SD; standard deviation, g/dl; gram per deciliter, mg/dl; milligrams per deciliter, g/d; grams per deciliter, ng/ml; nanograms per milliliter, and mg/l; milligrams per liter

Correlation between serum biomarkers and periodontal clinical parameters

In the present study, significant correlations were found between various serum biomarkers and periodontal clinical parameters. The Phosphorus level, the Creatinine level, the Albumin level and Haemoglobin level demonstrated significant correlations with the Plaque Index (p < 0.001, p < 0.001, p = 0.015, and p = 0.020) respectively. Notably, there was a significant negative correlation between serum albumin levels and the Plaque Index (r = -0.289, p = 0.015), indicating that higher plaque levels were associated with lower serum albumin levels. Similarly, ferritin levels were significantly negatively correlated with the Plaque Index (r = -0.281, p = 0.018) and with Miller Classes (r = -0.258, p = 0.031), suggesting that increased periodontal inflammation and tissue destruction were associated with higher serum ferritin levels. The Calcium level also showed a significant negative correlation with the Gingival Index (r = -0.266, p = 0.027), suggesting that gingival inflammation is inversely related to serum calcium levels. Also, the result showed a significant correlation between Creatinine levels and Periodontitis (r = 0.26, p = 0.03). However, no significant correlation was found between Periodontitis and other serum biomarkers (Tables: 3 and 4).

Discussion

The correlation between the level of plaque and the progression of periodontal disease exists, as supported by several evidences. [20, 21, 35] According to theses evidences, the inflammatory response caused by periodontitis can alter the host response in other parts of the body. [36]

Periodontitis has been proposed as a significant risk factor for CKD and renal failure due to its potential to induce systemic inflammation and the entry of periodontal bacteria into the bloodstream [37]. Thus, our study aimed to investigate the correlation between periodontal disease status and serum biomarkers in Yemeni patients undergoing haemodialysis. Biochemical markers such as albumin, calcium, phosphorus, haemoglobin, ferritin, creatinine, and Cystatin C, all related to renal function, were investigated in this study to assess the correlation between periodontal disease and systemic markers. Oral health of patients undergoing haemodialysis is often poor due to inadequate dental hygiene. [38]

Albumin is a marker of nutritional status and a reduction in serum albumin levels has been associated with increased morbidity and mortality in patients with chronic renal disease. [39] The relationship between periodontal disease and serum albumin levels is complex. While periodontitis can lead to systemic inflammation, which may affect albumin levels, it is also possible that low albumin levels in these patients contribute to the severity of their periodontal disease [40]. Previous studies have provided conflicting results regarding the association between periodontal disease and albumin levels in haemodialysis patients which was found that hemodialysis patients patients with severe periodontal disease were more than three times more likely to have low serum albumin than individuals with less severe disease [37]. These studies are in consistent with our results, the Albumin level showed a significant correlation with the Plaque Index (r = 0.289, p = 0.015).

Ferritin is an acute phase reactant, and its levels rise in the presence of systemic inflammation and used test for determining iron insufficiency in haemodialysis patients. [41, 42] Periodontal disease is characterized by chronic inflammation, which may contribute to elevated ferritin levels [43]. Furthermore, iron deficiency in cases of anaemia can also influence ferritin levels [43]. The association between ferritin levels and periodontal disease severity has been investigated in a few studies, but findings have been inconsistent. Some of these studies have found that the influence of inflammation on serum ferritin levels in haemodialysis patients is dependent on the body’s iron content and that inflammation affects serum ferritin only when the body’s iron concentration is sufficient [44]. Controversially, there is few studies with similar to our findings regarding the link between blood ferritin levels and periodontal disease in patients undergoing haemodialysis [27]. Our results showed a significant correlation with both the Plaque Index and Miller Classes with ferritin levels (r = 0.281, p = 0.018 and r = 0.258, p = 0.031) respectively.

The findings of our study revealed that there was a significant correlation between serum calcium levels and the gingival index (r = 0.266, p = 0.027). Calcium is crucial for maintaining the integrity of teeth and bones, and abnormalities in calcium levels can contribute to dental and skeletal problems [45]. In patients with chronic renal disease, abnormalities in calcium levels are common and can lead to vascular calcification and cardiovascular complications [46]. While the association between serum calcium levels and periodontal disease severity has been investigated in a few studies, the results have been inconsistent [47, 48].

Tavares et al. concluded that Cystatin C levels had a significant correlation with tooth mobility, indicating a potential association between periodontal disease and renal function [40] Similarly, periodontal disease can exacerbate renal insufficiency and contribute to elevated cystatin C levels [49]. In this context, our results found that Cystatin C levels showed a notable correlation with mobility (r = 0.258, p = 0.031). However, our results are contradicted with outcomes of Naghsh et al. who concluded that the level of Cystatin C increased with an increase in the severity of periodontal disease according to his analyses [27, 50].

Creatinine is an important marker of renal function and elevated levels are indicative of impaired renal function [51]. The association between periodontal disease and creatinine levels might be explained by the systemic effects of periodontal inflammation on renal function. Chronic inflammation can contribute to the progression of renal disease and impaired immune responses in haemodialysis patients can increase the risk of periodontal infection and inflammation [27].

It is important to acknowledge the limitations of this study. The cross-sectional design of the study, small sample size, and lack of data on the effect of periodontal disease treatment on kidney status are all factors that may have impacted the findings. Based on these limitations, we suggest that future research could benefit from a longitudinal study design with a larger sample size to better demonstrate a cause-and-effect relationship between chronic kidney diseases and periodontal diseases.

Conclusion

The present study provides evidence of an association between periodontal disease and chronic kidney disease in Yemeni patients undergoing haemodialysis. The findings revealed significant correlations between various serum biomarkers, including creatinine, albumin, ferritin, haemoglobin, phosphorus, and calcium, and periodontal clinical parameters. These associations highlight the potential systemic effects of periodontal disease in this population. The presence of periodontitis in all patients and the significant correlations observed demonstrate the importance of considering oral health in the management of chronic kidney disease.

Author contributions

M.M.B, B.A and S.A.E contributed to data collection, interpretation of data, designing the study and writing the original manuscript. M.A, H.M.A, and S.A.E have critically revised the manuscript. All other authors have approved the final one before its submission.

Funding

Not applicable.

Data availability

The datasets used and/or analyzed during the study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

The study protocol, which was ethically approved from the Ethical Committee of Medical Research at Sana’a University, has been conducted in accordance to the guidelines of the declaration of Helsinki. Written informed consent was obtained from all patients.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Maimona Mansour Basha first author.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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