Oral health status of children with chronic kidney diseases

Oral health status of children with chronic kidney diseases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Oral health status of children with chronic kidney diseases Anna Beyer, Fabian Ebach, Heiko Reutter, Katja Sauerstein, Alina Christine Hilger, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5439643/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Feb, 2025 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Introduction Chronic kidney disease (CKD) has been previously associated with a decline in oral health. This study aimed to examine the oral health of children with CKD, nephrotic syndrome (NS), and children that received kidney transplantation (KTR). Methods A case-control study was conducted involving children with CKD stages 1–3, children with CKD 4–5, pediatric kidney transplant recipients, and children with NS. Developmental Defects of Enamel (DDE) were evaluated using the DDE-Index, while dental caries was assessed with the Decayed Missing Filled Teeth Index (DMFT). Plaque and debris were measured utilizing the Simplified Oral Hygiene Index (OHI-S), which includes the two subindices Simplified Calculus Index (CI-S) and Simplified Debris Index (DI-S). Results Children with CKD 1–3, CKD 4–5, and KTR presented with significantly higher DI-S and CI-S score and significantly more DDE. There was no difference in the DMFT score in children with CKD 4–5 and KTR. For children with CKD 1–3, a significantly lower DMFT score was observed compared to the control group. Children with NS did not show any differences for DI-S, CI-S, DMFT, and DDE compared to healthy peers. Conclusion Oral health status is not affected in children with NS. Children with CKD 1–3, CKD 4–5, and KTR have more plaque, debris, and DDE and should be surveyed regularly by their dentists. Chronic kidney disease Kidney transplant recipients Nephrotic Syndrome DDE OHI-S DMFT Introduction With an estimated number of chronic kidney disease in children ranging from 15 to 74.7 per million, CKD represents a global issue in pediatric health care[ 1 ]. CKD can be classified into five stages based on the glomerular filtration rate [ 2 ]. In CKD V, also known as end stage kidney disease (ESKD), long-term survival requires dialysis or kidney transplantation [ 3 ]. CKD in children is associated with comorbidities such as failure to thrive, secondary hyperparathyroidism, hyperphosphatemia, metabolic acidosis, renal anemia [ 4 ]. Oral symptoms have already been associated with CKD in 1851[ 5 ]. These include lower dental caries scores, reduced salivary flow rate, high prevalence of calculus, debris, gingivitis, enamel hypoplasia, and a higher prevalence of developmental defects of enamel compared to their healthy peers [ 6 , 7 ]. Nephrotic syndrome (NS) in children is a rare disease that leads to proteinuria, hypoalbuminemia, edema, and hyperlipidemia [ 4 ]. Treatment unresponsiveness often leads to kidney failure. Around fifty per million children are affected by NS [ 8 ]. NS can be associated with severe gingivitis, partly more and partly less carious lesions, increased developmental defects in enamel, and increased accumulation of plaque and debris [ 9 , 10 ]. Given the prevalence of CKD, or NS, dentists, and medical care providers must be aware of the association of kidney diseases and dental diseases. Understanding this relationship is important as it directly impacts the effective management and treatment of oral manifestations, thereby improving the overall health outcome for these patients. This study aimed to examine oral health status by collecting carious, debris, calculus, and developmental defects of enamel scores in children with CKD, NS, and children with previous KTR in comparison to healthy peers. Material and Methods Ethical Approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Friedrich-Alexander Universität Erlangen-Nürnberg (06.2023/23-214-B). Before examining the patients, the parents or caregivers were informed about this study and signed an informed consent. Study population The oral health status of 167 children between four and seventeen years of age who had regular check-ups at the Center for Pediatric Nephrology and Dialysis at the University of Erlangen/Nuremberg was examined in this study. The children were divided into five groups: CKD stage 1-3, CKD stage 4-5, KTR, NS, and a group of healthy control peers. The children in the healthy control group did not have chronic kidney disease, a kidney transplantation or nephrotic syndrome. The glomerular filtration rate was determined according to the revised Schwartz Equation from 2009 as follows: eGFR (ml/min × 1.73 m 2 ) = 0.413 × Height (cm)/Serum Creatinine (mg/dl) [11]. The KDIGO nomenclature was used to classify children with CKD into the respective stages: Stage 1 with an eGFR ≥ 90 ml/min/1.73 m 2 , stage 2 with an eGFR between 60 and 89 ml/min/1.73 m 2 , stage 3 with an eGFR between 30 and 59 ml/min/1.73 m 2 , stage 4 with an eGFR between 15 and 29 ml/min/1.73 m 2 , stage 5 with an eGFR under 15 ml/min/1.73 m [2]. [2] Clinical data For each child, gender, date of birth, age, height, weight, serum creatinine level, and disease were recorded. Examination The examination was performed during a regular visit at the Center for Pediatric Nephrology and Dialysis at the University of Erlangen/Nuremberg. Each examination started with an informative conversation about the study with a parent or caregiver and the child, and informed consent was given from the parent or caregiver. An oral mirror and dental loupes with light were used for every intraoral examination. The examination took about two to three minutes. Indices Decayed Missing Filled Teeth Index (DMFT) The DMFT index determines the prevalence of dental caries. Therefore, a sum is formed by adding the number of decayed teeth due to caries, missing teeth due to caries, and filled teeth. The index is written small in the primary dentition (dmft) and in capital letters in the permanent dentition (DMFT). In mixed dentition, only permanent teeth are considered (DMFT). [12] In this paper, the DMFT index is not considered separately for primary and permanent dentition. Simplified Oral Hygiene Index (OHI-S) The OHI-S index is used to determine dental calculus and debris. It has two subindices, the Calculus index (CI-S) and the Debris index (DI-S). Overall, six tooth surfaces are examined: 16 vestibular, 26 vestibular, 11 vestibular, 36 lingual, 46 lingual and 11 lingual. In total, there are four stages: stage 0 no calculus, or debris; stage 1 calculus or debris covers the gingival third of the tooth; stage 2 calculus or debris covers 1/3 to 2/3 of the gingival tooth surface; stage 3 debris or calculus covers more than 2/3 of the tooth surface. Each of the six tooth surfaces is assigned a stage for the CI-S index. These six stages are added and divided by six, meaning the number can range from zero to three. Afterward, the same is done for the DI-S index. Lastly, the CI-S and DI-S results are added to receive the OHI-S index, meaning the number can range from zero to six. [13, 14] Developmental Defects of Enamel (DDE) The Federation Dental International provides this index [15]. In this study, children could either have no developmental defects of enamel, diffuse developmental defects of enamel, or demarcated developmental defects of enamel. Statistical Analysis Statistical analysis was performed using R version 4.3.0 [16]. Dental indices between each disease group and the control group were compared using individual Wilcoxon rank sum tests followed by Bonferroni correction for multiple comparisons. Results As shown in Table 1, 167 children were included in this study. Among them, 81 were healthy controls, 31 were diagnosed with CKD 1-3, 17 with CKD 4-5, 17 had previous KTR, and 21 were affected by NS. The median age in the healthy group was 9 years; in the CKD 1-3 group it was 11 years; in the CKD 4-5 group it was 10 years; in the KTR, it was 12 years; and of NS, it was 8 years. Table 1. Distribution of the participants Group n Age p-value Control 81 (48,5%) 9 [7;13] CKD 1-3 31 (18,6%) 11 [8;15] 0,399 CKD 4-5 17 (10,2%) 10 [5.75;14.25] 0.97 KTR 17 (10,2%) 12 [10;14] 0.387 NS 21 (12,6%) 8 [7;12] 0.97 * Significant difference at p < 0.05, Median [IQR] In Table 2 the median DMFT score is displayed. The healthy group had a median DMFT score of 1, the children with CKD 1-3 and CKD 4-5 had a median DMFT score of 0, the KTR had a median DMFT score of 2, and the children with NS of 2. The carious status was non-significant for the CKD 4-5, KTR, and NS compared to the healthy group (p>0.05). However, the DMFT score differed significantly between the CKD 1-3 and the healthy group (p=0.019). Table 2. DMFT Group DMFT p-value Control 1 [0;2] CKD 1-3 0 [0;0.5] 0.019 * CKD 4-5 0 [0;1] 0.312 KTR 2 [1;4] 0.057 NS 2 [0;3] 0.312 * Significant difference at p < 0.05, Median [IQR] Table 3 shows the groups' CI-S, DI-S, and OHI-S scores. Higher median CI-S scores could be observed in the CKD 1-3 group (CI-S= 0.67), in the CKD 4-5 group (CI-S= 1), in the KTR group (CI-S= 0.83), and in the NS group (CI-S= 0.33) compared to the control group (CI-S= 0.17). There was a significant association in the median CI-S score between CKD 1-3, CKD 4-5, and KTR, and the control group in contrast to the NS group, where no significant correlation could be viewed for the median CI-S score compared to the healthy group. The group of healthy control peers had a median DI-S score of 0.33. In comparison, children with CKD 1-3, CKD 4-5, KTR, and NS all expressed a higher median DI-S score than the healthy group (CKD 1-3: 0.83; CKD 4-5: 1; KTR: 0.67; NS: 0.5). This was significant for all groups except for the NS group. Subsequently, the OHI-S score, which is composed of the DI-S score and the CI-S score, was higher compared to the control group in all four groups. In comparison to their healthy peers, the OHI-S score was significant for the CKD 1-3, CKD 4-5, and KTR group except for the NS group. Table 3. OHI-S, DI-S, CI-S Group CI-S (p value) DI-S (p-value) OHI-S (p-value) Control 0.17 [0;0.5] 0.33 [0;0,5] 0.5 [0;1] CKD 1-3 0.67 [0.5;1] (<0.001 ****) 0.83 [0.5;1] (<0.001 ****) 1.5 [1;2] (<0.001 ****) CKD 4-5 1 [0.5;2] (<0.001 ****) 1 [1;1.5] (<0.001 ****) 2 [1.5;3.33] (<0.001 ****) KTR 0.83 [0.29;1] (<0.001 ***) 0.67 [0.33;1] (0.004 **) 1.33 [0.83;2] (<0.001 ***) NS 0.33 [0;0.5] (0.332) 0.5 [0.33;0.67] (0.072) 0.83 [0.33;1.17] (0.129) * Significant difference at p < 0.05, Median [IQR] The distribution of DDE is presented in Table 4 . In this study, 72% of the healthy children, 45% of the children with CKD 1-3, 29% of the children with CKD 4-5, 24% KTR, and 71 % of the children with NS expressed no DDE. Twenty-five % of the healthy children, 35% of the CKD 1-3 group, 41% of the CKD 4-5 group, 29% of the KTR group, and 14% of the NS group exhibited demarcated DDE. Diffuse DDE were observed in 4% of the children in the healthy group, 19% in the CKD 1-3 group, 24% in the CKD 4-5 group, 47% in the KTR group, and 14% in the NS group. A statistically significant relationship was found between these observations for the CKD 1-3, CKD 4-5, and KTR group. No statistical significance was observed for the children with NS. Table 4. DDE Developmental defects of enamel Group No Diffuse Demarcated p Control 58 (72%) 20 (25%) 3 (4%) CKD 1-3 14 (45%) 11 (35%) 6 (19%) 0.008 ** CKD 4-5 5 (29%) 7 (41%) 4 (24%) 0.002 ** KTR 4 (24%) 5 (29%) 8 (47%) <0.001 **** NS 15 (71%) 3 (14%) 3 (14%) 0.781 * Significant difference at p < 0.05, Median [IQR] Discussion This study aimed to examine the oral health status of children with CKD, previous KTR, or NS and compared it to a group of healthy control peers. Several studies have recently highlighted the influence of CKD and kidney transplantation on oral health status [7, 17, 18]. However, the present study included probably the largest group of healthy control peers and included a relatively large number of children with previous KTR [7]. One crucial factor of oral health is its impact on quality of life, such as dental caries, decreasing school performance, and sleeping problems [19]. Understanding the relationship between oral health and CKD, kidney transplantation, NS, DMFT is relevant to optimizing these children’s overall health and quality of life. In this study three oral impairments were examined: DDE, OHI-S and DMFT. First, we focused on DDE. DDE occur when ameloblasts are damaged or their metabolic activity is disturbed during enamel formation. These defects are irreversible and can be diffuse or demarcated [12]. The disrupted metabolic activity in CKD can be attributed to hypocalcemia [4], hyperphosphatemia [4], decreased serum levels of 1,25-dihydroxycholecalciferol [20], and fluorosis [21] [18]. Just as several studies have presented that there is a higher prevalence of DDE in children with CKD [6, 22, 23] the present study confirmed these findings highlighting the importance of disrupted metabolic activity in children with CKD [4, 12, 20, 21]. Studies have indicated that children with NS exhibit more developmental defects of enamel than those without the condition [9, 10]. Nevertheless, our study did not support this finding. We observed that children with NS did not show a difference in DDE compared to healthy peers. However; in our study we did not divide children with NS into subgroups of different clinical courses and etiologies. Children with NS show changes in calcium, Vitamin D, and phosphate metabolism [24, 25] which could be a reason that children with NS have more DDE. Second, we focused on debris and calculus. Debris refers to a structured, yellowish dental plaque composed of microorganisms embedded within a protein matrix and a polysaccharide-based matrix. Failure to remove plaque through regular tooth brushing and interdental cleaning leads to calculus formation. Calculus is mineralized debris [26]. Saliva in children with CKD has a higher pH level and contains elevated amounts of urea and phosphorus, which then combine to form calcium-phosphorus and calcium oxalate [18]. As in other studies who indicated that children with CKD have more calculus and debris accumulation than healthy children [6, 7] , our study confirmed this observation. The higher debris and plaque accumulation is due to the higher pH level of the saliva in children with CKD and KTR[18]. For children with NS, the prevalence was higher in debris and calculus in other studies [9, 10]. Our study did not show differences compared to the healthy peers. The higher levels in debris and calculus in other studies could be due to a raised pH level in the saliva of this group [27]. Third, we focused on dental caries. Dental caries is a process caused by cariogenic bacteria, particularly Streptococcus mutans, which form a biofilm on the tooth surface. These bacteria metabolize carbohydrates, producing acids that gradually demineralize the tooth surface. The process is dynamic, involving cycles of demineralization and remineralization, with demineralization predominating over time. Children with CKD often experience xerostomia [28], reduced saliva flow [6]. Furthermore, they seem to have a higher intake of unhealthy foods, such as takeaway meals [29], compared to their healthy peers. Although these factors would typically indicate a higher likelihood of developing caries, this could not be observed in recent studies. Numerous studies have investigated the occurrence of dental caries in children with CKD, whereby most have found that the DMFT score is lower in these children compared to a healthy control group [6, 7, 23, 30]. Additionally, two studies examined the oral health of children undergoing hemodialysis and reported differing results. One study found that the incidence of dental caries was higher in these children [31], while the other study found it to be lower [32]. Our study revealed that children with CKD 1-3 and CKD 4-5 had fewer dental caries than the control group, though this difference was not statistically significant for the children with CKD 4-5. Conversely, children who underwent kidney transplantation had more dental caries in our study than the control group, however, this was non-significant. This was not the case in another recent study where the children with kidney transplantation had a lower DMFT score than the control group [22]. The lower DMFT score in children with CKD could be attributed to a more alkaline oral pH of the saliva and a reduced presence of Streptococcus mutans [33, 34]. The higher pH level of the saliva worsens the environment for the cariogenic bacteria, leading to a slower formation of dental caries [18]. The higher DMFT score (non-significant) in our research of children with KTR compared to their healthy peers could be due to increased Streptococcus mutans levels following transplantation [33], which could lead to a rise in the primary cariogenic bacteria in the biofilm which could be investigated in future studies. The carious score in NS was higher [9] but lower [10] in another study. Our study showed non-significant higher dental carious scores. A recent study found that children with idiopathic NS had Streptococcus mutans levels comparable to their healthy peers. This suggests that children with NS are not expected to have more carious lesions than the healthy peers [10]. Our study has several limitations. The groups were small, only representing a fraction of the patients with CKD 1-3, CKD 4-5, those who had undergone kidney transplantation and NS. Group combination was performed as five groups would have led to very small sample size in each group. Classification in these CKD groups was based on clinical features, as patients with CKD 1-3 classically do not have severe clinical problems, whereas patients with CKD 4-5 suffer from different comorbidities. Therefore, it appeared likely that combining these groups could be sufficient to demonstrate statistical differences. Moreover, the children with idiopathic NS were not divided into subgroups of different clinical courses and etiologies. Additionally, dental caries was examined visually without an orthopantomogram. Due to this, interproximal caries could have been overseen. Furthermore, the study did not assess the number or severity of developmental defects of enamel. It did not pay attention to other comorbidities that could impact oral health. On the contrary, this study employs reproducible indices. This ensures consistent examinations and the possibility of comparing it to other studies. Additionally, the control group and the group of kidney transplant recipients were bigger than in other studies. In conclusion, children with CKD and KTR have dental disease and oral health problems in a considerable number of cases highlighting the structural defects of enamel in CKD. Furthermore, debris, plaque and DDE are also increased. However, NS does not have a significant impact on children’s oral health in our study. Pediatricians and medical caregivers must be aware of these implications and refer children with CKD and KTR to dentists on a regular basis. Additionally, parental consultation should include the explanation that DDE and a higher number of debris and calculus are common in children with CKD and those who have received kidney transplants compared to healthy children. Declarations Disclosures Nothing to disclose Acknowledgement We would like to thank everyone involved in data collection, all parents for their cooperation in this study. For this work, J. T. S. and A. C. H. were supported by the Else Kröner-Fresenius Stiftung and the Eva Luise und Horst Köhler Stiftung—Project No: 2019_KollegSE.04 and supported by the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg (Junior Project “J98”). References Warady BA, Chadha V (2007) Chronic kidney disease in children: the global perspective. 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Int J Pediatr Dent 14:118–126. https://doi.org/10.1111/j.1365-263X.2004.00534.x Ertuğrul F, Elbek-Cubukçu C, Sabah E, Mir S (2003) The oral health status of children undergoing hemodialysis treatment. Turk J Pediatr 45:108–113 Cite Share Download PDF Status: Published Journal Publication published 04 Feb, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Major Revisions Needed 02 Dec, 2024 Reviewers agreed at journal 13 Nov, 2024 Reviewers invited by journal 12 Nov, 2024 Editor assigned by journal 12 Nov, 2024 First submitted to journal 12 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Beyer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYLACxgYQyXwMzGFjJ14LWxoDQwKQYiZeC48ZWAsDIS38s3sPfmDcYZPYL33m24OPP7bJ8zEzMH74mINbi8Sdc8kSjGfSEmf25W43nJFw27CNmYFZcuY2PNbcyDGQ/tt2OHHDGd5t0jwJtxmBWtiYefFokb+RY/yDse1/4v4zPM9AWuwJajG4kWMmwdh2IHEDDw8bSEsiQS2GQC0WjGeSjWecYTOTnJF2O7mNmbEZr1/kgA67wbjDTra/h/mZxAeb27bz25sPfviIz/tQ4NiAYDM24FKFAuyJUjUKRsEoGAUjEwAAAhdNOP4C6VwAAAAASUVORK5CYII=","orcid":"","institution":"Friedrich Alexander University Erlangen Nuremberg: Friedrich-Alexander-Universitat Erlangen-Nurnberg","correspondingAuthor":true,"prefix":"","firstName":"Anna","middleName":"","lastName":"Beyer","suffix":""},{"id":377449446,"identity":"c2024fae-ac0a-4259-a34a-e081522917f1","order_by":1,"name":"Fabian Ebach","email":"","orcid":"","institution":"Zentrum für Kinderheilkunde der Universität Bonn: Zentrum fur Kinderheilkunde der Universitat Bonn","correspondingAuthor":false,"prefix":"","firstName":"Fabian","middleName":"","lastName":"Ebach","suffix":""},{"id":377449447,"identity":"e3cdc43b-4c1f-4c45-912c-561f508df866","order_by":2,"name":"Heiko Reutter","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Heiko","middleName":"","lastName":"Reutter","suffix":""},{"id":377449448,"identity":"87caf8dd-0215-4e26-98e9-b7220d2beca0","order_by":3,"name":"Katja Sauerstein","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Katja","middleName":"","lastName":"Sauerstein","suffix":""},{"id":377449449,"identity":"c27f395c-f140-4736-b147-20286c06e8ad","order_by":4,"name":"Alina Christine Hilger","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Alina","middleName":"Christine","lastName":"Hilger","suffix":""},{"id":377449450,"identity":"6f1abaa6-50fa-47c0-afab-a5f6ab341a24","order_by":5,"name":"Tobias Krickau","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Tobias","middleName":"","lastName":"Krickau","suffix":""},{"id":377449451,"identity":"c9b12e4e-0f3a-483c-91a6-57f4431638a1","order_by":6,"name":"Anja Tzschoppe","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Anja","middleName":"","lastName":"Tzschoppe","suffix":""},{"id":377449452,"identity":"60df0f50-e35d-4a1a-9c28-4f86f15f6cd4","order_by":7,"name":"Joachim Woelfe","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Joachim","middleName":"","lastName":"Woelfe","suffix":""},{"id":377449453,"identity":"9ef56c08-05ad-47a5-9831-bc6b272f0cfc","order_by":8,"name":"Matthias Galiano","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Matthias","middleName":"","lastName":"Galiano","suffix":""},{"id":377449454,"identity":"70350c02-a187-464a-ac19-f7132f4f6826","order_by":9,"name":"Jan Thomas Schaefer","email":"","orcid":"","institution":"Universitätsklinikum Erlangen Kinder- und Jugendklinik: Universitatsklinikum Erlangen Kinder- und Jugendklinik","correspondingAuthor":false,"prefix":"","firstName":"Jan","middleName":"Thomas","lastName":"Schaefer","suffix":""}],"badges":[],"createdAt":"2024-11-12 12:40:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5439643/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5439643/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-06698-1","type":"published","date":"2025-02-04T15:58:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":75931282,"identity":"fd7a7d98-c736-4f13-b036-506ca8ae2c99","added_by":"auto","created_at":"2025-02-10 16:14:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":471122,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5439643/v1/c4141524-fcb1-4ac3-a53c-7dbd1b499fca.pdf"}],"financialInterests":"","formattedTitle":"Oral health status of children with chronic kidney diseases","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWith an estimated number of chronic kidney disease in children ranging from 15 to 74.7 per million, CKD represents a global issue in pediatric health care[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. CKD can be classified into five stages based on the glomerular filtration rate [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In CKD V, also known as end stage kidney disease (ESKD), long-term survival requires dialysis or kidney transplantation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCKD in children is associated with comorbidities such as failure to thrive, secondary hyperparathyroidism, hyperphosphatemia, metabolic acidosis, renal anemia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Oral symptoms have already been associated with CKD in 1851[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These include lower dental caries scores, reduced salivary flow rate, high prevalence of calculus, debris, gingivitis, enamel hypoplasia, and a higher prevalence of developmental defects of enamel compared to their healthy peers [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nephrotic syndrome (NS) in children is a rare disease that leads to proteinuria, hypoalbuminemia, edema, and hyperlipidemia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Treatment unresponsiveness often leads to kidney failure. Around fifty per million children are affected by NS [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. NS can be associated with severe gingivitis, partly more and partly less carious lesions, increased developmental defects in enamel, and increased accumulation of plaque and debris [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the prevalence of CKD, or NS, dentists, and medical care providers must be aware of the association of kidney diseases and dental diseases. Understanding this relationship is important as it directly impacts the effective management and treatment of oral manifestations, thereby improving the overall health outcome for these patients. This study aimed to examine oral health status by collecting carious, debris, calculus, and developmental defects of enamel scores in children with CKD, NS, and children with previous KTR in comparison to healthy peers.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eEthical Approval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Friedrich-Alexander Universität Erlangen-Nürnberg (06.2023/23-214-B). Before examining the patients, the parents or caregivers were informed about this study and signed an informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudy population\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe oral health status of 167 children between four and seventeen years of age who had regular check-ups at the Center for Pediatric Nephrology and Dialysis at the University of Erlangen/Nuremberg was examined in this study. The children were divided into five groups: CKD stage 1-3, CKD stage 4-5, KTR, NS, and a group of healthy control peers. The children in the healthy control group did not have chronic kidney disease, a kidney transplantation or nephrotic syndrome. The glomerular filtration rate was determined according to the revised Schwartz Equation from 2009 as follows: eGFR (ml/min × 1.73\u0026nbsp;m\u003csup\u003e2\u003c/sup\u003e) = 0.413 × Height (cm)/Serum Creatinine (mg/dl) [11]. The KDIGO nomenclature was used to classify children with CKD into the respective stages: Stage 1 with an eGFR\u0026nbsp;≥ 90 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, stage 2 with an eGFR between 60 and 89 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, stage 3 with an eGFR between 30 and 59 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, stage 4 with an eGFR between 15 and 29 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, stage 5 with an eGFR under 15 ml/min/1.73 m [2].\u0026nbsp;[2]\u003c/p\u003e\n\u003cp\u003eClinical data\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor each child, gender, date of birth, age, height, weight, serum creatinine level, and disease were recorded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eExamination\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe examination was performed during a regular visit at the Center for Pediatric Nephrology and Dialysis at the University of Erlangen/Nuremberg. Each examination started with an informative conversation about the study with a parent or caregiver and the child, and informed consent was given from the parent or caregiver. An oral mirror and dental loupes with light were used for every intraoral examination. The examination took about two to three minutes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIndices\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDecayed Missing Filled Teeth Index (DMFT)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe DMFT index determines the prevalence of dental caries. Therefore, a sum is formed by adding the number of decayed teeth due to caries, missing teeth due to caries, and filled teeth. The index is written small in the primary dentition (dmft) and in capital letters in the permanent dentition (DMFT). In mixed dentition, only permanent teeth are considered (DMFT). [12] In this paper, the DMFT index is not considered separately for primary and permanent dentition.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSimplified Oral Hygiene Index (OHI-S)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe OHI-S index is used to determine dental calculus and debris. It has two subindices, the Calculus index (CI-S) and the Debris index (DI-S). Overall, six tooth surfaces are examined: 16 vestibular, 26 vestibular, 11 vestibular, 36 lingual, 46 lingual and 11 lingual. In total, there are four stages: stage 0 no calculus, or debris; stage 1 calculus or debris covers the gingival third of the tooth; stage 2 calculus or debris covers 1/3 to 2/3 of the gingival tooth surface; stage 3 debris or calculus covers more than 2/3 of the tooth surface. Each of the six tooth surfaces is assigned a stage for the CI-S index. These six stages are added and divided by six, meaning the number can range from zero to three. Afterward, the same is done for the DI-S index. Lastly, the CI-S and DI-S results are added to receive the OHI-S index, meaning the number can range from zero to six. [13, 14]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDevelopmental Defects of Enamel (DDE)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Federation Dental International provides this index [15]. In this study, children could either have no developmental defects of enamel, diffuse developmental defects of enamel, or demarcated developmental defects of enamel.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical Analysis\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using R version 4.3.0 [16]. Dental indices between each disease group and the control group were compared using individual Wilcoxon rank sum tests followed by Bonferroni correction for multiple comparisons.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAs shown in \u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e1, 167 children were included in this study. Among them, 81 were healthy controls, 31 were diagnosed with CKD 1-3, 17 with CKD 4-5, 17 had previous KTR, and 21 were affected by NS. The median age in the healthy group was 9 years; in the CKD 1-3 group it was 11 years; in the CKD 4-5 group it was 10 years; in the KTR, it was 12 years; and of NS, it was 8 years.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 605px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Distribution of the participants \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 203px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eAge\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 203px;\"\u003e\n \u003cp\u003eControl \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e81 (48,5%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e9 [7;13]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 203px;\"\u003e\n \u003cp\u003eCKD 1-3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e31 (18,6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e11 [8;15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0,399\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 203px;\"\u003e\n \u003cp\u003eCKD 4-5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e17 (10,2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e10 [5.75;14.25]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.97\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 203px;\"\u003e\n \u003cp\u003eKTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e17 (10,2%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e12 [10;14]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.387\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 203px;\"\u003e\n \u003cp\u003eNS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e21 (12,6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e8 [7;12]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 605px;\"\u003e\n \u003cp\u003e* Significant difference at p \u0026lt; 0.05, Median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIn \u003cstrong\u003eTable 2\u003c/strong\u003e the median DMFT score is displayed. The healthy group had a median DMFT score of 1, the children with CKD 1-3 and CKD 4-5 had a median DMFT score of 0, the KTR had a median DMFT score of 2, and the children with NS of 2. The carious status was non-significant for the CKD 4-5, KTR, and NS compared to the healthy group (p\u0026gt;0.05). However, the DMFT score differed significantly between the CKD 1-3 and the healthy group (p=0.019).\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e DMFT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eDMFT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003eControl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e1 [0;2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003eCKD 1-3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0 [0;0.5]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.019 *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003eCKD 4-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0 [0;1]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003eKTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e2 [1;4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 31px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e2 [0;3]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e* Significant difference at p \u0026lt; 0.05, Median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e shows the groups\u0026apos; CI-S, DI-S, and OHI-S scores. Higher median CI-S scores could be observed in the CKD 1-3 group (CI-S= 0.67), in the CKD 4-5 group (CI-S= 1), in the KTR group (CI-S= 0.83), and in the NS group (CI-S= 0.33) compared to the control group (CI-S= 0.17). There was a significant association in the median CI-S score between CKD 1-3, CKD 4-5, and KTR, and the control group in contrast to the NS group, where no significant correlation could be viewed for the median CI-S score compared to the healthy group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe group of healthy control peers had a median DI-S score of 0.33. In comparison, children with CKD 1-3, CKD 4-5, KTR, and NS all expressed a higher median DI-S score than the healthy group (CKD 1-3: 0.83; CKD 4-5: 1; KTR: 0.67; NS: 0.5). This was significant for all groups except for the NS group. Subsequently, the OHI-S score, which is composed of the DI-S score and the CI-S score, was higher compared to the control group in all four groups. In comparison to their healthy peers, the OHI-S score was significant for the CKD 1-3, CKD 4-5, and KTR group except for the NS group. \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e OHI-S, DI-S, CI-S\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003eCI-S\u003c/p\u003e\n \u003cp\u003e(p value)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003eDI-S\u003c/p\u003e\n \u003cp\u003e(p-value)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003eOHI-S\u003c/p\u003e\n \u003cp\u003e(p-value)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.17 [0;0.5]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.33 [0;0,5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.5 [0;1]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eCKD 1-3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.67 [0.5;1]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ****)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.83 [0.5;1]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ****)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.5 [1;2]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ****)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eCKD 4-5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1 [0.5;2]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ****)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1 [1;1.5]\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ****)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e2 [1.5;3.33]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ****)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eKTR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.83 [0.29;1]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ***)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.67 [0.33;1]\u003c/p\u003e\n \u003cp\u003e(0.004 **)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.33 [0.83;2]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u0026lt;0.001 ***)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eNS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.33 [0;0.5]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.332)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.5 [0.33;0.67]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.072)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.83 [0.33;1.17]\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.129)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e* Significant difference at p \u0026lt; 0.05, Median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe distribution of DDE is presented in \u003cstrong\u003eTable 4\u003c/strong\u003e. In this study, 72% of the healthy children, 45% of the children with CKD 1-3, 29% of the children with CKD 4-5, 24% KTR, and 71 % of the children with NS expressed no DDE. \u0026nbsp;Twenty-five % of the healthy children, 35% of the CKD 1-3 group, 41% of the CKD 4-5 group, 29% of the KTR group, and 14% of the NS group exhibited demarcated DDE. Diffuse DDE were observed in 4% of the children in the healthy group, 19% in the CKD 1-3 group, 24% in the CKD 4-5 group, 47% in the KTR group, and 14% in the NS group. A statistically significant relationship was found between these observations for the CKD 1-3, CKD 4-5, and KTR group. No statistical significance was observed for the children with NS. \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4.\u003c/strong\u003e DDE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 53px;\"\u003e\n \u003cp\u003eDevelopmental defects of enamel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003eDiffuse\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eDemarcated\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eControl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e58 (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e20 (25%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e3 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eCKD 1-3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e14 (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e11 (35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e6 (19%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.008 **\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eCKD 4-5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e5 (29%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e7 (41%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e4 (24%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.002 **\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eKTR\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e4 (24%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e5 (29%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e8 (47%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u0026lt;0.001 ****\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003eNS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e15 (71%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e3 (14%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e3 (14%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.781\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e* Significant difference at p \u0026lt; 0.05, Median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aimed to examine the oral health status of children with CKD, previous KTR, or NS and compared it to a group of healthy control peers. Several studies have recently highlighted the influence of CKD and kidney transplantation on oral health status [7, 17, 18]. However, the present study included probably the largest group of healthy control peers and included a relatively large number of children with previous KTR [7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOne crucial factor of oral health is its impact on quality of life, such as dental caries, decreasing school performance, and sleeping problems [19]. Understanding the relationship between oral health and CKD, kidney transplantation, NS, DMFT is relevant to optimizing these children\u0026rsquo;s overall health and quality of life. In this study three oral impairments were examined: DDE, OHI-S and DMFT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFirst, we focused on DDE. DDE\u0026nbsp;occur when ameloblasts are damaged or their metabolic activity is disturbed during enamel formation. These defects are irreversible and can be diffuse or demarcated [12]. The disrupted metabolic activity in CKD can be attributed to hypocalcemia [4], hyperphosphatemia [4], decreased serum levels of 1,25-dihydroxycholecalciferol [20], and fluorosis [21]\u0026nbsp;[18]. Just\u0026nbsp;as several studies have presented that there is a higher prevalence of DDE in children with CKD\u0026nbsp;[6, 22, 23]\u0026nbsp;the present study confirmed these findings highlighting the importance of disrupted metabolic activity in children with CKD\u0026nbsp;[4, 12, 20, 21]. Studies have indicated that children with NS exhibit more developmental defects of enamel than those without the condition [9, 10]. Nevertheless, our study did not support this finding. We observed that children with NS did not show a difference in DDE compared to healthy peers. However; in our study we did not divide children with NS into subgroups of different clinical courses and etiologies. Children with NS show changes in calcium, Vitamin D, and phosphate metabolism\u0026nbsp;[24, 25]\u0026nbsp;which could be a reason that children with NS have more DDE.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSecond, we focused on debris and calculus. Debris refers to a structured, yellowish dental plaque composed of microorganisms embedded within a protein matrix and a polysaccharide-based matrix. Failure to remove plaque through regular tooth brushing and interdental cleaning leads to calculus formation. Calculus is mineralized debris [26]. Saliva in children with CKD has a higher pH level and contains elevated amounts of urea and phosphorus, which then combine to form calcium-phosphorus and calcium oxalate [18]. As in other studies who indicated that children with CKD have more calculus and debris accumulation than healthy children [6, 7] , our study confirmed this observation. The higher debris and plaque accumulation is due to the higher pH level of the saliva in children with CKD and KTR[18]. For children with NS, the prevalence was higher in debris and calculus in other studies [9, 10]. Our study did not show differences compared to the healthy peers. The higher levels in debris and calculus in other studies could be due to a raised pH level in the saliva of this group\u0026nbsp;[27].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThird, we focused on dental caries. Dental caries is a process caused by cariogenic bacteria, particularly Streptococcus mutans, which form a biofilm on the tooth surface. These bacteria metabolize carbohydrates, producing acids that gradually demineralize the tooth surface. The process is dynamic, involving cycles of demineralization and remineralization, with demineralization predominating over time. Children with CKD often experience xerostomia [28], reduced saliva flow [6]. Furthermore, they seem to have a higher intake of unhealthy foods, such as takeaway meals [29], compared to their healthy peers. Although these factors would typically indicate a higher likelihood of developing caries, this could not be observed in recent studies. Numerous studies have investigated the occurrence of dental caries in children with CKD, whereby most have found that the DMFT score is lower in these children compared to a healthy control group [6, 7, 23, 30]. Additionally, two studies examined the oral health of children undergoing hemodialysis and reported differing results. One study found that the incidence of dental caries was higher in these children [31], while the other study found it to be lower [32]. Our study revealed that children with CKD 1-3 and CKD 4-5 had fewer dental caries than the control group, though this difference was not statistically significant for the children with CKD 4-5. Conversely, children who underwent kidney transplantation had more dental caries in our study than the control group, however, this was non-significant. This was not the case in another recent study where the children with kidney transplantation had a lower DMFT score than the control group [22]. The lower DMFT score in children with CKD could be attributed to a more alkaline oral pH of the saliva and a reduced presence of Streptococcus mutans [33, 34]. The higher pH level of the saliva worsens the environment for the cariogenic bacteria, leading to a slower formation of dental caries [18]. The higher DMFT score (non-significant) in our research of children with KTR compared to their healthy peers could be due to increased Streptococcus mutans levels following transplantation [33], which could lead to a rise in the primary cariogenic bacteria in the biofilm which could be investigated in future studies. The carious score in NS was higher [9]\u0026nbsp;but lower\u0026nbsp;[10]\u0026nbsp;in another study. Our study showed non-significant higher dental carious scores. A recent study found that children with idiopathic NS had Streptococcus mutans levels comparable to their healthy peers. This suggests that children with NS are not expected to have more carious lesions than the healthy peers\u0026nbsp;[10].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. The groups were small, only representing a fraction of the patients with CKD 1-3, CKD 4-5, those who had undergone kidney transplantation and NS. Group combination was performed as five groups would have led to very small sample size in each group. Classification in these CKD groups was based on clinical features, as patients with CKD 1-3 classically do not have severe clinical problems, whereas patients with CKD 4-5 suffer from different comorbidities. Therefore, it appeared likely that combining these groups could be sufficient to demonstrate statistical differences. Moreover, the children with idiopathic NS were not divided into subgroups of different clinical courses and etiologies. Additionally, dental caries was examined visually without an orthopantomogram. Due to this, interproximal caries could have been overseen. Furthermore, the study did not assess the number or severity of developmental defects of enamel. It did not pay attention to other comorbidities that could impact oral health. On the contrary, this study employs reproducible indices. This ensures consistent examinations and the possibility of comparing it to other studies. Additionally, the control group and the group of kidney transplant recipients were bigger than in other studies.\u003c/p\u003e\n\u003cp\u003eIn conclusion, children with CKD and KTR have dental disease and oral health problems in a considerable number of cases highlighting the structural defects of enamel in CKD. Furthermore, debris, plaque and DDE are also increased. However, NS does not have a significant impact on children\u0026rsquo;s oral health in our study. Pediatricians and medical caregivers must be aware of these implications and refer children with CKD and KTR to dentists on a regular basis. Additionally, parental consultation should include the explanation that DDE and a higher number of debris and calculus are common in children with CKD and those who have received kidney transplants compared to healthy children.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eDisclosures\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNothing to disclose\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgement\u003c/p\u003e\n\u003cp\u003eWe would like to thank everyone involved in data collection, all parents for their cooperation in this study. For this work, J. T. S. and A. C. H. were supported by the Else Kröner-Fresenius Stiftung and the Eva Luise und Horst Köhler Stiftung—Project No: 2019_KollegSE.04 and supported by the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg (Junior Project “J98”).\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWarady BA, Chadha V (2007) Chronic kidney disease in children: the global perspective. 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Turk J Pediatr 45:108\u0026ndash;113\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Chronic kidney disease, Kidney transplant recipients, Nephrotic Syndrome, DDE, OHI-S, DMFT","lastPublishedDoi":"10.21203/rs.3.rs-5439643/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5439643/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eChronic kidney disease (CKD) has been previously associated with a decline in oral health. This study aimed to examine the oral health of children with CKD, nephrotic syndrome (NS), and children that received kidney transplantation (KTR).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA case-control study was conducted involving children with CKD stages 1\u0026ndash;3, children with CKD 4\u0026ndash;5, pediatric kidney transplant recipients, and children with NS. Developmental Defects of Enamel (DDE) were evaluated using the DDE-Index, while dental caries was assessed with the Decayed Missing Filled Teeth Index (DMFT). Plaque and debris were measured utilizing the Simplified Oral Hygiene Index (OHI-S), which includes the two subindices Simplified Calculus Index (CI-S) and Simplified Debris Index (DI-S).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eChildren with CKD 1\u0026ndash;3, CKD 4\u0026ndash;5, and KTR presented with significantly higher DI-S and CI-S score and significantly more DDE. There was no difference in the DMFT score in children with CKD 4\u0026ndash;5 and KTR. For children with CKD 1\u0026ndash;3, a significantly lower DMFT score was observed compared to the control group. Children with NS did not show any differences for DI-S, CI-S, DMFT, and DDE compared to healthy peers.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOral health status is not affected in children with NS. Children with CKD 1\u0026ndash;3, CKD 4\u0026ndash;5, and KTR have more plaque, debris, and DDE and should be surveyed regularly by their dentists.\u003c/p\u003e","manuscriptTitle":"Oral health status of children with chronic kidney diseases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-05 05:42:34","doi":"10.21203/rs.3.rs-5439643/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2024-12-02T19:01:15+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-11-13T05:00:56+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-13T03:56:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-12T19:03:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2024-11-12T07:39:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"08dfbb50-1921-4263-af5d-21f84c163b20","owner":[],"postedDate":"December 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T16:10:12+00:00","versionOfRecord":{"articleIdentity":"rs-5439643","link":"https://doi.org/10.1007/s00467-025-06698-1","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-02-04 15:58:24","publishedOnDateReadable":"February 4th, 2025"},"versionCreatedAt":"2024-12-05 05:42:34","video":"","vorDoi":"10.1007/s00467-025-06698-1","vorDoiUrl":"https://doi.org/10.1007/s00467-025-06698-1","workflowStages":[]},"version":"v1","identity":"rs-5439643","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5439643","identity":"rs-5439643","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}