Association Between Endodontics Alterations and Transplanted Patients or Those in Need of Kidney or Liver Transplantation: A Scoping ReviewABSTRACT
Objective: To investigate clinical studies that evaluated the relationship between endodontic alterations and transplanted patients or those in need of liver or kidney transplantation compared to patients not in need of transplantation.
Material and Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two independent authors conducted an electronic search of the main databases until January 2025. Clinical studies evaluating endodontic changes in transplant patients were included in this study. There was no restriction on the date of publication.
Results: Among the 332 studies retrieved, 11 studies were included. Two cross-sectional studies assessed the interrelationship between patients undergoing liver transplantation and endodontic changes. Nine studies evaluated the relationship between kidney transplantation and endodontic changes; two studies found no relationship between pulp calcification and these patients; however, another three studies found a relationship between the chronicity of the actual disease and pulp chamber narrowing.
Conclusion: Few clinical studies have evaluated the interrelationship between patients of liver transplantation and endodontic changes; studies that have evaluated the interrelationship between patients of kidney transplantation have found a relationship mainly with pulp chamber narrowing, but no relationship with pulp calcifications.
Keywords:
Kidney Transplantation; Liver Transplantation; Oral Health; Dental Pulp Necrosis.
Introduction
Several factors can affect the pulp tissue, including unsuccessful restorative dental procedures, dental trauma, or caries [1,2]. The dental pulp is irrigated by blood vessels through the main periapical foramen or several foramina. When the pulpal circulatory system collapses, or if the aggressor is not removed correctly and in a timely manner, irreversible damage to the dental pulp and its structure may occur [3,4]. As the inflammatory process reaches the periapical tissues, a bone resorption process begins. If endodontic treatment is not carried out, there will be bacteria and microorganisms from the root canal system present [3,4].
Studies suggest that there may be a relationship between some systemic diseases and oral diseases [3,5,6]. A relationship between oral changes in patients who had undergone transplants, especially kidney and liver, was identified [7-9]. Immunosuppressed patients due to kidney transplantation may present unregulated levels of cytokines in the blood [7-9]. A study showed that increased serum urea levels were significantly associated with periapical lesions in these patients. Authors observed a prevalence of periapical lesions 75% higher in patients with kidney diseases, compared to the control group [6]. However, the study highlights that patients with kidney failure can have bone problems caused by other alterations, which can confuse the real origin of the issue [6].
Grønkjær et al. [10] showed that almost half of the patients with liver cirrhosis had periapical radiolucency. In this study, patients with periapical lesions of endodontic origin had a higher prevalence of other systemic complications. According to the authors, these dental problems could become a source of bacteria, which would result in a small inflammation that would lead to systemic implications in the future [9-12].
Apparently, few studies have evaluated the bidirectional relationship between systemic changes in transplant patients with endodontic infections. It is necessary to understand whether there is an association between endodontic changes and transplanted patients or those in need of kidney or liver transplantation. Thus, the objective of this scope review is to identify all the studies already carried out on this theme, to understand if there is a relationship.
Material and Methods
Registration Protocol
The scoping review was carried out strictly following the PRISMA-ScR checklist (PRISMA Extension for Scoping Reviews), as described by Tricco et al. [13] (Supplementary Table 1). The study protocol was registered on the Open Science Framework platform and is available at the following link: https://osf.io/uhc8f/.
Eligibility Criteria
The inclusion criteria were (1) studies that evaluated endodontic alterations in transplanted patients or those who needed kidney or liver transplants; (2) clinical studies; (3) studies published in English. The exclusion criteria were as follows: (1) in vitro studies; (2) animal studies; (3) case reports; (4) studies involving transplanted patients with other involved organs; (5) duplicate studies; (6) literature review; (7) studies whose full texts were unavailable to the authors.
Information Sources and Search Strategy Details
PubMed was screened using search terms pertinent to the research question. A search strategy using Boolean operators was used to identify papers using MeSH, keywords, and other free terms: “(periapical lesion or apical periodontitis OR dental pulp OR pulp tissue) AND (liver OR kidney) AND (transplant patients OR chronic disease)”.
The search was conducted using four electronic databases: MEDLINE (PubMed), EMBASE, and Cochrane Library from the inception date of January 2025. No filter for the date was placed to ensure that all relevant articles were included. In addition, the reference lists of the included studies were also screened for any additional relevant articles.
Study Selection Strategy
Following the removal of duplicates and screening of the titles and abstracts of articles, potentially relevant studies were retrieved. If the title and abstract were not sufficient to determine inclusion or exclusion, the full text was read for a final decision. All full-text studies were independently assessed to determine whether they fulfilled the inclusion and exclusion criteria and were processed for data extraction.
Data Extraction
The two primary reviewers (H.G.S.C. and M.R.M.) extracted data independently. The following data were extracted: first author’s last name, year of publication, study design, groups, sample size, objectives and type of analysis. Discrepancies were resolved by discussion with a third author (F.B.).
Data Analysis
Textural data findings (verbatim extracts) were retrieved from the included studies and subsequently synthesized.
Quality Assessment
No quality assessment was performed in accordance with the PRISMA guidelines for scoping reviews.
Results
Selection Sources of Evidence
Three hundred and thirty-two qualified articles were initially identified in the literature search. After the first screening (Stage 1), 20 studies were selected for full-text evaluation (Stage 2). Of these, nine articles were excluded. Finally, 11 studies met the inclusion criteria and were included for qualitative analysis [6,14-23]. Figure 1 shows a schematic representation of the selection process.
Study Characteristics
The characteristics of the studies are shown in Table 1. According to the study design, 10 studies were cross-sectional [6,14,22], and 1 study was a cohort [23]. The average number of patients in the studies was approximately 1193, with one study having 12,454 patients [23].
A total of 2 studies evaluated patients for liver transplantation [21,22], while nine studies evaluated patients for kidney transplantation [6,14-20,23]. Among the studies evaluated, 10 performed radiographic analysis to determine the size of the lesion [6,14-20,22]. A total of 3 studies carried out clinical analyses [18,20,21] and two studies applied questionnaires [18,20]. Table 1 also summarizes the results of the analyses carried out in each study included in this scoping review.
Only two studies have assessed the interrelationship between the need for liver transplantation and endodontic changes [21,22]. Both were cross-sectional studies and showed poor patient oral hygiene. One of the studies [22] showed a greater presence of apical periodontitis and a lower number of endodontically treated teeth, which was associated with inadequate oral hygiene care. In addition, the treatment of oral alterations was associated with a possible reduction in the mortality of these patients.
Relationship with Kidney Transplantation
Nine studies have evaluated [6,14-20,23] the relationship between kidney transplantation and endodontic changes. One study [23] evaluated and showed that patients who received endodontic treatment had a relatively lower risk of death among dialysis patients. Another study [6] showed that apical periodontitis was significantly more prevalent in the group with end-stage renal disease.
Two other studies [18,20] pointed out that the oral health of dialysis patients is poor and requires greater attention. The two studies [19,20] that assessed the relationship with pulp calcification found no such assessment or difference with healthy patients.
However, three other studies [15-17] that evaluated pulp chamber narrowing found a relationship between the chronicity of the actual disease and this narrowing; this result was associated with the use of corticosteroids. Another study [14] found changes in bone tissue, but not in relation to endodontics.
Discussion
This scoping review evaluated the interrelationship between endodontic alterations and patients of liver or kidney transplantation. It was observed that few studies have analyzed the interrelationship between alterations in patients of liver transplantation and endodontic alterations, which need to be better evaluated. With regard to patients of kidney transplantation, more studies have been carried out, but with a great deal of heterogeneity.
The association between dental infections and general health has been evaluated in several studies [24,25]. For example, there is evidence to suggest that metabolic syndrome and diabetes can alter the oral microbiome [26]; chronic apical periodontitis and endodontic therapy play a role in the development of systemic outcomes [27] and coronary heart disease [28]; and there is an association of chronic systemic medications with the incidence, prevalence or cure of endodontic disease [29].
The periapical infectious process consists of local tissue responses, but is not exclusively a local phenomenon [24]. However, although many studies have evaluated the endodontic relationship mainly with coronary heart disease and diabetes, few have evaluated this relationship with organ transplant patients.
In general, it is known that the poor state of oral health observed in the majority of patients requiring transplantation represents a source of systemic infections before and after transplantation, and that the treatment of oral infections is associated with a reduction in mortality in these patients [21]. In this review, two cross-sectional studies showed poor oral hygiene in patients undergoing liver transplants [21,22]. One of the studies showed a greater presence of periapical lesions [22], while another showed that the treatment of oral alterations was associated with a possible reduction in mortality in these patients [21]. Physical, behavioral and social factors can contribute to these results, due to concerns about medical issues, demotivation, anxiety, depression, as well as the use of medications that reduce salivary flow [30,31]. This highlights the care that professionals must take with these patients, encouraging them and constantly making them aware of oral hygiene.
In relation to kidney transplants, more studies were found in this review, but with very different objectives. One study showed that patients who received endodontic treatment had a relatively lower risk of death among dialysis patients [23]. Another study showed that apical periodontitis was significantly more prevalent in the group with end-stage renal disease [6], which corroborates two other studies that pointed out that the oral health of dialysis patients is precarious and requires greater attention [18,20]. The reasons may be similar to those previously reported for liver transplant patients.
Two studies evaluated the relationship with pulp calcification and did not find this association [18,20]. There is a conflict in the association between the presence of pulp calcification and systemic alterations. For example, one study confirmed the increase in pulp calcifications in patients with coronary atherosclerosis on radiographic examination [32], and another study suggested that the presence or absence of pulp stones could be used to screen for cardiovascular diseases [33]. However, studies with updated and improved methodologies need to be carried out.
On the other hand, three other studies of this review that evaluated pulp chamber narrowing found a relationship between chronic kidney disease and this narrowing [15-17]. This result was associated with the use of corticosteroids. A study showed that rats treated with cortisone showed more hard tissue formation in the dental pulp chamber [34], and Näsström et al. [17] showed that pulp chamber narrowing was observed mainly in patients receiving high doses of prednisone. Shinozuka et al. [35] also observed narrowing of the pulp cavity in patients undergoing prolonged steroid administration. This study, therefore, draws the attention of the endodontist who may foresee a narrow pulp chamber in patients who need a transplant, which can make the root canal localization procedure more difficult.
In any case, it is crucial to establish protocols aimed at effectively treating apical periodontitis in all teeth, thus mitigating the risk of complications in patients requiring transplantation. This proactive approach to the oral health of pre-transplant patients will contribute to the success and safety of subsequent dental procedures.
Conclusion
Few studies have looked at the relationship between patients requiring liver transplantation and endodontic alterations. While in cases of kidney transplantation, an association was observed with narrowing of the pulp chamber, no correlations were found with pulp calcifications. Further research is crucial to clarify the interrelationship between endodontic alterations and organ transplant candidates.
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Financial Support
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001 and Process n. 88887.712700/2022-00; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Grant n. 310683/2022-0; and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Fapemig), process APQ-04630-23.
Data Availability
The data used to support the findings of this study can be made available upon request to the corresponding author.
References
-
[1] Chaves HGS, Souza LML, Macedo IFA, Maia CA, Figueiredo B, Ferreira IC, et al. Regenerative therapy in teeth with incomplete root formation after dental trauma to tooth 21: A case report. RSD 2022; 11:e11911729033. https://doi.org/10.33448/rsd-v11i7.29033
» https://doi.org/10.33448/rsd-v11i7.29033 -
[2] Chaves HGS, Moreira TPC, Figueiredo B, Macedo IFA, Ferreira IC, Maia CA, et al. Pulp calcification in traumatized teeth - A literature review. RSD 2022; 11:e36011729293. https://doi.org/10.33448/rsd-v11i7.29293
» https://doi.org/10.33448/rsd-v11i7.29293 -
[3] Sasaki H, Hirai K, Martins CM, Furusho H, Battaglino R, Hashimoto K. Interrelationship between periapical lesion and systemic metabolic disorders. Curr Pharm Des 2016; 22(15):2204-2215. https://doi.org/10.2174/1381612822666160216145107
» https://doi.org/10.2174/1381612822666160216145107 -
[4] Galler KM, Weber M, Korkmaz Y, Widbiller M, Feuerer M. Inflammatory response mechanisms of the dentine-pulp complex and the periapical tissues. Int J Mol Sci 2021; 22(3):1480. https://doi.org/10.3390/ijms22031480
» https://doi.org/10.3390/ijms22031480 -
[5] Peng X, Cheng L, You Y, Tang C, Ren B, Li Y, et al. Oral microbiota in human systematic diseases. Int J Oral Sci 2022; 14(1):14. https://doi.org/10.1038/s41368-022-00163-7
» https://doi.org/10.1038/s41368-022-00163-7 -
[6] Khalighinejad N, Aminoshariae A, Kulild JC, Sahly K, Mickel A. Association of end-stage renal disease with radiographically and clinically diagnosed apical periodontitis: A hospital-based study. J Endod 2017; 43(9):1438-1441. https://doi.org/10.1016/j.joen.2017.04.014
» https://doi.org/10.1016/j.joen.2017.04.014 -
[7] Olczak-Kowalczyk D, Gozdowski D, Pawłowska J, Grenda R. The status of dental and jaw bones in children and adolescents after kidney and liver transplantation. Ann Transplant 2012; 17(4):72-81. https://doi.org/10.12659/aot.883697
» https://doi.org/10.12659/aot.883697 -
[8] Osiak M, Szubińska-Lelonkiewicz D, Wychowański P, Karakulska-Prystupiuk E, Jędrzejczak W, Wojtowicz A, et al. Frequency of pathologic changes in the oral cavity in patients subjected to long-term pharmacologic immunosuppressive therapy after kidney, liver, and hematopoietic cell transplantation. Transplant Proc 2018; 50(7):2176-2178. https://doi.org/10.1016/j.transproceed.2018.04.003
» https://doi.org/10.1016/j.transproceed.2018.04.003 -
[9] Bajaj JS, Shamsaddini A, Acharya C, Fagan A, Sikaroodi M, Gavis E, et al. Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis. Gut Microbes 2021; 13(1):1993584. https://doi.org/10.1080/19490976.2021.1993584
» https://doi.org/10.1080/19490976.2021.1993584 -
[10] Grønkjær LL, Holmstrup P, Schou S, Schwartz K, Kongstad J, Jepsen P, et al. Presence and consequence of tooth periapical radiolucency in patients with cirrhosis. Hepat Med 2016; 8:97-103. https://doi.org/10.2147/HMER.S113485
» https://doi.org/10.2147/HMER.S113485 -
[11] Belstrøm D, Damgaard C, Nielsen CH, Holmstrup P. Does a causal relation between cardiovascular disease and periodontitis exist? Microbes Infect 2012; 14(5):411-418. https://doi.org/10.1016/j.micinf.2011.12.004
» https://doi.org/10.1016/j.micinf.2011.12.004 -
[12] Niazi SA, Bakhsh A. Association between endodontic infection, its treatment and systemic health: A narrative review. Medicina 2022; 58(7):931. https://doi.org/10.3390/medicina58070931
» https://doi.org/10.3390/medicina58070931 -
[13] Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med 2018; 169(7):467-473. https://doi.org/10.7326/M18-0850
» https://doi.org/10.7326/M18-0850 -
[14] Kelly WH, Mirahmadi MK, Simon JH, Gorman JT. Radiographic changes of the jawbones in end stage renal disease. Oral Surg Oral Med Oral Pathol 1980; 50(4):372-381. https://doi.org/10.1016/0030-4220(80)90423-5
» https://doi.org/10.1016/0030-4220(80)90423-5 -
[15] Näsström K, Forsberg B, Petersson A, Westesson PL. Narrowing of the dental pulp chamber in patients with renal diseases. Oral Surg Oral Med Oral Pathol 1985; 59(3):242-246. https://doi.org/10.1016/0030-4220(85)90159-8
» https://doi.org/10.1016/0030-4220(85)90159-8 -
[16] Galili D, Berger E, Kaufman E. Pulp narrowing in renal end stage and transplanted patients. J Endod 1991; 17(9):442-443. https://doi.org/10.1016/S0099-2399(07)80133-6
» https://doi.org/10.1016/S0099-2399(07)80133-6 -
[17] Näsström K, Möller B, Petersson A. Effect on human teeth of renal transplantation: A postmortem study. Scand J Dent Res 1993; 101(4):202-209. https://doi.org/10.1111/j.1600-0722.1993.tb01105.x
» https://doi.org/10.1111/j.1600-0722.1993.tb01105.x - [18] Klassen JT, Krasko BM. The dental health status of dialysis patients. J Can Dent Assoc 2002; 68(1):34-38.
-
[19] Kansu O, Ozbek M, Avcu N, Aslan U, Kansu H, Gençtoy G. Can dental pulp calcification serve as a diagnostic marker for carotid artery calcification in patients with renal diseases? Dentomaxillofac Radiol 2009; 38(8):542-545. https://doi.org/10.1259/dmfr/13231798
» https://doi.org/10.1259/dmfr/13231798 - [20] Kanjanabuch P, Sinpitaksakul P, Chinachatchawarat S, Pacharapong S, Kanjanabuch T. Oral and radiographic findings in patients undergoing continuous ambulatory peritoneal dialysis. J Med Assoc Thai 2011; 94(Suppl 4):S106-112.
-
[21] Lins L, Bittencourt PL, Evangelista MA, Lins R, Codes L, Cavalcanti AR, et al. Oral health profile of cirrhotic patients awaiting liver transplantation in the Brazilian Northeast. Transplant Proc 2011; 43(4):1319-1321. https://doi.org/10.1016/j.transproceed.2011.03.063
» https://doi.org/10.1016/j.transproceed.2011.03.063 -
[22] Castellanos-Cosano L, Machuca-Portillo G, Segura-Sampedro JJ, Torres-Lagares D, López-López J, Velasco-Ortega E, et al. Prevalence of apical periodontitis and frequency of root canal treatments in liver transplant candidates. Med Oral Patol Oral Cir Bucal 2013; 18(5):e773-779. https://doi.org/10.4317/medoral.19148
» https://doi.org/10.4317/medoral.19148 -
[23] Chiu CC, Chang YC, Huang RY, Chan JS, Chung CH, Chien WC, et al. Investigation of the impact of endodontic therapy on survival among dialysis patients in Taiwan: A nationwide population-based cohort study. Int J Environ Res Public Health 2021; 18(1):326. https://doi.org/10.3390/ijerph18010326
» https://doi.org/10.3390/ijerph18010326 -
[24] Cintra LTA, Gomes MS, da Silva CC, Faria FD, Benetti F, Cosme-Silva L, et al. Evolution of endodontic medicine: A critical narrative review of the interrelationship between endodontics and systemic pathological conditions. Odontology 2021; 109(4):741-769. https://doi.org/10.1007/s10266-021-00636-x
» https://doi.org/10.1007/s10266-021-00636-x -
[25] Segura-Egea JJ, Cabanillas-Balsera D, Martín-González J, Cintra LTA. Impact of systemic health on treatment outcomes in endodontics. Int Endod J 2023; 56(Suppl 2):219-235. https://doi.org/10.1111/iej.13789
» https://doi.org/10.1111/iej.13789 -
[26] Pirih FQ, Monajemzadeh S, Singh N, Sinacola RS, Shin JM, Chen T, et al. Association between metabolic syndrome and periodontitis: The role of lipids, inflammatory cytokines, altered host response, and the microbiome. Periodontol 2000 2021; 87(1):50-75. https://doi.org/10.1111/prd.12379
» https://doi.org/10.1111/prd.12379 -
[27] Heikkilä P, Niskanen L, But A, Sorsa T, Haukka J. Oral health associated with incident diabetes but not other chronic diseases: A register-based cohort study. Front Oral Health 2022; 3:1031500. https://doi.org/10.3389/foh.2022.1031500
» https://doi.org/10.3389/foh.2022.1031500 -
[28] Paju S, Pietiäinen M, Liljestrand JM, Lahdentausta L, Salminen A, Kopra E, et al. Carotid artery calcification in panoramic radiographs associates with oral infections and mortality. Int Endod J 2021; 54(1):15-25. https://doi.org/10.1111/iej.13394
» https://doi.org/10.1111/iej.13394 -
[29] Alghofaily M, Fouad AF. Association of chronic systemic medications with the incidence, prevalence, or healing of endodontic disease: A systematic review. J Endod 2022; 48(12):1458-1467. https://doi.org/10.1016/j.joen.2022.10.004
» https://doi.org/10.1016/j.joen.2022.10.004 -
[30] Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, et al. IL-10, IL-6, and TNF-alpha: Central factors in the altered cytokine network of uremia-the good, the bad, and the ugly. Kidney Int 2005; 67(4):1216-1233. https://doi.org/10.1111/j.1523-1755.2005.00200.x
» https://doi.org/10.1111/j.1523-1755.2005.00200.x -
[31] Helenius-Hietala J, Meurman JH, Höckerstedt K, Lindqvist C, Isoniemi H. Effect of the aetiology and severity of liver disease on oral health and dental treatment prior to transplantation. Transpl Int 2012; 25(2):158-165. https://doi.org/10.1111/j.1432-2277.2011.01381.x
» https://doi.org/10.1111/j.1432-2277.2011.01381.x -
[32] Maranhão de Moura AA, de Paiva JG. Pulpal calcifications in patients with coronary atherosclerosis. Endod Dent Traumatol 1987; 3(6):307-309. https://doi.org/10.1111/j.1600-9657.1987.tb00640.x
» https://doi.org/10.1111/j.1600-9657.1987.tb00640.x -
[33] Edds AC, Walden JE, Scheetz JP, Goldsmith LJ, Drisko CL, Eleazer PD. Pilot study of correlation of pulp stones with cardiovascular disease. J Endod 2005; 31(7):504-506. https://doi.org/10.1097/01.don.0000168890.42903.2b
» https://doi.org/10.1097/01.don.0000168890.42903.2b -
[34] Anneroth G, Bloom G. Structural changes in the incisors of cortisone-treated rats. J Dent Res 1966; 45(2):229-235. https://doi.org/10.1177/00220345660450020301
» https://doi.org/10.1177/00220345660450020301 -
[35] Shinozuka O, Sekiguchi G, Tamamori Y, Inada M, Yamazaki T, Ohyama T. Narrowing of the dental pulp cavity in patients undergoing long-term administration of steroids. Kokubyo Gakkai Zasshi 2001; 68(4):294-299. https://doi.org/10.5357/koubyou.68.294 [In Japanese].
» https://doi.org/10.5357/koubyou.68.294
Edited by
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Academic Editor:
Alessandro Leite Cavalcanti
