Key words : Kidney transplantation, Liver transplantation, Pediatric patients

Introduction

Chronic liver disease is characterized by the progressive deterioration of the liver, which has functions such as detoxification of harmful metabolic products, bile excretion, and synthesis of various proteins.¹ Like chronic liver disease, chronic kidney disease is associated with progression to renal failure, complications related to reduced renal function, and cardiovascular disease.² The global prevalence of chronic kidney disease is estimated at approximately 10% of the general population.³

Currently, the most effective and important treatment for end-stage organ failure is organ transplant.⁴ Because of improved medical care and advances in immunosuppressive therapy, the survival of patients after transplant has increased.⁵ Various developmental and acquired findings have been observed in the craniofacial region of patients with systemic and chronic diseases with increasing age. Patients who continue intensive drug use, hospitalization, and transplant treatments are expected to experience various oral symptoms at some point in their lives. Various dental findings (dental caries, green coloration of teeth, gingival bleeding, tooth sensitivity, gingival hyperplasia, enamel hypoplasia, and dentofacial anomalies) specific to the drugs used, concomitant diseases, and ongoing immunosuppression have been observed in organ transplant recipients.^4,6 The risk of infection increases in patients because of lifelong use of immunosuppressive drugs posttransplant. Dental infections also have an important place among infections seen in transplant recipients.⁴ Therefore, determining the dental status of transplanted patients and providing dental care are highly important for preventing infections.

Given the high prevalence of both chronic kidney disease and chronic liver disease, dentists are likely to encounter affected patients. Dentists should be familiar with the oral and systemic manifestations of chronic kidney disease and chronic liver disease, as well as the clinical management and follow-up appointment frequencies.^7,8

Although a few studies are available in the literature on odontogenic anomalies, dental caries status (DMFT/dmft), and the effects of immunosup-pressive agents used on dental status in pediatric kidney and liver transplant patients, to our knowledge, no study is available on dental age determination.^4,9-11

In this study, we aimed to assess the effects of liver and kidney transplant, along with the subsequent immunosuppressive treatment, on dental age and the incidence of dental caries and tooth and bone anomalies in transplant recipients.

Materials and Methods

Ethics approval and consent to participate
This study was a retrospective study, and only basic clinical information and imaging data of patients were collected. No clinical intervention was performed, and no disclosure of personal privacy occurred. All methods were performed in accordance with the relevant guidelines and regulations. The Institutional Review Board of Baskent University (project No. D-KA 23/08) approved the study. We conducted the study in accordance with the Declaration of Helsinki and the General Data Protection Regulation. Patient information was anonymized and deidentified before analysis. Patients included in this study signed a written informed consent to undergo the examination.

Patients
We conducted a retrospective study of pediatric patients who underwent liver or kidney transplant at Baskent University Hospital between January 2011 and December 2023. The study was performed at the Baskent University Faculty of Dentistry, Department of Pedodontics. We included pediatric patients aged 6 to 12 years. Patients who died and had no available clinical or radiological examination data were excluded from the study. In total, 92 patients (65 liver transplant recipients, 27 kidney transplant recipients) met the inclusion criteria and were included in the study (Figure 1).

We retrospectively evaluated patient data on dental structure (eg, caries, odontogenic anomalies) and clinical and radiographic data of jaw bones. We examined patient demographic characteristics (age, sex, height, weight, and body mass index), time after transplant, comorbidities, type and dose of immuno-suppressive agents used, need for periodontal treatment, need for orthodontic treatment, dental examination information before and after transplant, and time since the last dental examination. We compared all data in liver transplant versus kidney transplant patients.

Panoramic radiographs
Panoramic radiographs (Morita Veraviewepocs 2DCP, J. Morita Inc) were used for radiologic evaluation.

Dental age determination
Dental age was determined after panoramic radiog-raphs were converted to TIFF format in grayscale via the InterPacs program (13.2.19401.1661, Health Solutions Industry Trade Limited Company) and saved as photographs; only mandibular molars were evaluated with the Demirjian method to evaluate the stages of tooth development more clearly.¹²

Dental caries
The incidence of dental caries was evaluated with dmft in primary teeth and with DMFT in permanent teeth, with DMFT/dmft as total number of decayed, extracted, and filled teeth due to decay. We determined the incidence of caries in the percentage of patients with DMFT/dmft >0.

Odontogenic anomalies
We evaluated the presence and type of odontogenic anomalies (number, size, shape, structural anomalies, and presence of enamel defects in the teeth), caries, pulp chamber (pulp stones), and bone status.

Statistical analyses
We used SPSS version 22 (IBM SPSS Statistics for Windows) to analyze data. We presented results as means ± SD and median (range) for quantitative variables and as number of patients (percentage) for qualitative variables. We used the Kolmogorov-Smirnov test to test normality of distribution. To determine differences between 2 categories of quantitative variables, we used the t test if the assumption of a normal distribution was met and the Mann-Whitney U test if the assumption was not met. We used X² and Fisher exact tests to examine relationship between 2 qualitative variables. Significance level was accepted as P < .05.

Results

Patient characteristics
Among the 92 patients included in the study, 65 had liver transplant and 27 had kidney transplant (Figure 1). The average ages of the liver and kidney transplantpatients were 7.35 ± 2.81 and 9.48 ± 3.50 years, respectively (P = .033). No differences between groups were shown in body mass index (P = .572). Accompanying comorbidities, especially hypertension (P = .001) and thyroid diseases (P = .023), were signi-ficantly more common in kidney transplant patients. Although mycophenolate mofetil as an immunosup-presive agent was found to be similar in terms of use by patients in both groups (P = .338), tacrolimus and glucocorticoids were used more by liver transplant patients (P < .001 and P = .037, respectively). Although average daily dose of immuno-suppressive agents was greater in liver transplant patients taking gluco-corticoids (P < .001), daily dose was greater in kidney transplant patients taking mycophenolate mofetil or tacrolimus (P = .037 and P < .001, respectively). Patient characteristics are listed in (Table 1).

Dental examination information
Although the percentage of liver transplant patients who underwent dental examinations pretransplant was lower than the percentage of kidney transplant patients (P = .024), no differences between groups were shown in terms of number of patients who underwent dental examinations posttransplant (P = .743). When we examined the time since last dental examination in both liver transplant and kidney transplant patients, most had last visit at >12 months (Table 2).

Clinical and radiological findings
Average dental ages of patients who underwent liver and kidney transplant, as determined by the Demirjian method, were 7.90 ± 3.17 and 9.63 ± 3.17 years, respectively, with no significant difference between groups (P = .068). Dental age did not lag behind chronological age in either group. Although groups were not different in terms of DMFT and dmft (P = .123 and P = .095, respectively), dental caries were significantly greater in liver transplant patients (P = .006) (Figure 2). Tubercle deformity was only observed in kidney transplant patients (P = .033). Groups were not significantly different in terms of other odontogenic anomalies (P > .05). Pulp stones and jaw bone anomalies were not observed in any liver transplant patient. The need for periodontal and orthodontic treatment was similar between groups (P = .151 and P = .512, respectively). Findings are summarized in (Table 3).

(Table 4) lists clinical and radiological findings in patients with and without dental caries. Patients with dental caries were mostly liver transplant recipients and those with a low percentage of persistent teeth.

Odontogenic and jaw anomalies were more frequently shown in patients who used mycophenolate mofetil at high doses (P = .008). In addition, accom-panying comorbidities were more common in patients with odontogenic and jaw anomalies (P = .023). (Table 5) shows comparisons between patients with and without odontogenic and jaw anomalies.

Logistic regression analysis showed that, among the independent variables affecting dental caries, only type of transplant had a significant effect (P = .007, odds ratio = 3.927; 95% CI, 1.447-10.657). In terms of presence of odontogenic and jaw anomalies, average daily dose of mycophenolate mofetil and comorbidities had no significant effect according to logistic regression analysis (P = .094 and P = .538, respectively) (Table 6).

Discussion

In our evaluation of oro-dental findings and dental age in pediatric patients who underwent liver and kidney transplant, presence of dental caries was higher in liver transplant than in kidney transplant patients. Only tubercle deformity was found to be higher in kidney transplant than in liver transplant patients in terms of odontogenic and jaw anomalies. In addition, dental age was not behind chronological age in either group.

Children with liver failure exhibit malnutrition, hypoproteinaemia, impaired calcium and phosphorus absorption, and abnormal vitamin D metabolism; in children with chronic renal failure, disorders in bone metabolism occur because of decreased 1,25-dihydroxycholecalciferol production, hypocalcemia, hyperphosphatemia, and hyperparathyroidism.⁴

Immunosuppressive agents used in organ transplant recipients are responsible for potentially harmful side effects, especially in developing children. They affect bone tissue metabolism by inhibiting calcitonin secretion, reducing growth hormone secretion, and disrupting bone formation. Glucocorticoids, which are immunosuppressive agents, activate osteoclasts, inhibit osteoblasts, and increase magnesium and calcium excretion by preventing calcium absorption from the intestine. Immunosuppressive agents reduce serum 25-hydroxyvitamin D concentration in children, leading to deterioration of skeletal mineralization and thus osteoporosis and osteopenia. Similarly, calcineurin inhibitors (tacrolimus and cyclosporin A) have been reported to be associated with increased bone resorption.⁴

Oral lesions that occur after kidney or liver transplant are manifestations of chronic disease-related systemic complications that were present before the transplant and are subsequently affected by immunosuppression. The incidence of some oral lesions is related to the specific type of organ transplant and maintenance immunosuppression.⁴

The higher incidence of dental caries in liver transplant than in kidney transplant patients in our study is similar to that reported by Olczak-Kowalczyk and colleagues.⁴ Similarly, Seow and colleagues¹³ and Shiboski and colleagues¹⁴ reported that the prevalence of caries was high in children who underwent liver transplant. Other studies have shown that children with kidney disease have a low prevalence of caries.^9,10,14-17 All of these findings coincide with the results of our study.

Kwak and colleagues reported that liver transplant recipients had worse oral hygiene than kidney transplant recipients,¹⁸ which may suggest that liver and kidney diseases have different systemic effects. This idea is supported by the fact that, in kidney transplant recipients, the risk of caries is lower due to the breakdown of urea in saliva to form ammonia, which increases the oral pH above the critical level for demineralization of tooth enamel.^10,13 Moreover, the higher rate of kidney transplant recipients who underwent pretransplant dental examinations in our study may have led to a lower incidence of dental caries.

Similar to the findings of our study, odontogenic and jaw anomalies have been observed in both kidney and liver transplant recipients.^4,16,19 Both liver and kidney transplant recipients have been shown to have more odontogenic and jaw anomalies than the general population. One factor that may cause this condition is the disordered calcium and phosphate balance and metabolism in these patients, which may be due to conditions existing before organ transplant or to the use of immunosuppressive agents after transplant.⁴ In our study, tubercle deformity, an odontogenic defect, was observed only in kidney transplant patients, which is consistent with the literature.^4,10 The negative effects of calcium-phosphate metabolism due to nutritional deficiency (especially hypoalbuminemia and hypomagnesemia) may develop after kidney transplant and may explain our finding.¹⁰

In our study, odontogenic and jaw anomalies were observed more frequently among patients who used mycophenolate mofetil at a higher average daily dose and who had more comorbidities. This can be explained by the fact that additional systemic disorders in children affect bone and calcium-phosphate metabolism, disrupting odontogenesis and the occurrence of jaw bone anomalies. These findings also suggest that mycophenolate mofetil may cause bone abnormalities in a dose-dependent manner.²⁰

One study noted that tooth eruption was delayed in transplant recipients.⁴ However, in our study, no difference was found between dental age and chronological age. This may be due to differences in factors such as the age at which end-stage organ failure occurred, the duration of the disease, and the type, dose, and duration of immunosuppressive agents.

To the best of our knowledge, this study is the first comparative analysis of oral and dental health among pediatric patients who have undergone liver or kidney transplant in Turkey. Although a notable strength of our study is inclusion of a larger patient cohort than found in previous studies on transplant recipients, our study had limitations. First, the absence of a healthy control group may affect the robustness of the findings. Second, certain data were incomplete because of our study’s retrospective design, including patient body surface area, kidney and liver function values, and etiologies leading to liver and kidney damage. Finally, the median time posttransplant for kidney transplant patients was relatively short (4.5 months) compared with time for liver transplant patients, which may limit the ability to fully capture the effects of immunosuppressive agents on oro-dental health in kidney transplant recipients.

Despite several limitations inherent in our study, our findings contribute to the advancement of future clinical research concerning the importance of regular dental check-ups for pediatric patients who have undergone liver and kidney transplant.

Conclusions

Our study demonstrated that dental caries are more prevalent among liver transplant patients, irrespective of the type and dosage of immunosuppressive agent administered. Furthermore, the dosage of mycop-henolate mofetil was found to influence the occurrence of tooth and jaw anomalies. In addition to medical management, regular follow-up and dental care must be prioritized for transplant recipients before and after transplant to ensure optimal oral health outcomes.

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