Anxiety And Depression Symptomatology In Adolescents With Kidney Disorders During Pediatric-To-Adult Transition: “Perception Of Illness” And The “Patient Paradox”

Anxiety And Depression Symptomatology In Adolescents With Kidney Disorders During Pediatric-To-Adult Transition: “Perception Of Illness” And The “Patient Paradox” | 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 Anxiety And Depression Symptomatology In Adolescents With Kidney Disorders During Pediatric-To-Adult Transition: “Perception Of Illness” And The “Patient Paradox” Dorella Scarponi, Marta Tremolada, Pasquale Castaldo, Roberto Pillon, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9284328/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 5 You are reading this latest preprint version Abstract Background The transition from pediatric to adult care represents a critical phase for adolescents with chronic kidney disease (CKD), potentially affecting both clinical management and psychological well-being. This study aimed to evaluate anxiety and depressive symptoms in adolescents with CKD undergoing a structured transition program and to identify clinical and demographic predictors of psychological distress. Psychological outcomes were also compared with those of a healthy age- and sex-matched control group. Methods A cross-sectional monocentric study was conducted at the Pediatric Nephrology and Dialysis Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna- Policlinico di Sant’Orsola, Bologna, Italy. The study included 93 adolescents and young adults with kidney disorders (mean age 17.4 ± 1.4 years) enrolled in a structured transition program. Psychological assessment was performed using BDI-II and STAI-S and T. A healthy control group (n = 186) was selected using propensity score matching (1:2 ratio) based on age and sex. Statistical analyses included t-tests, ANOVA, and multivariate linear regression models. Results Most patients reported minimal depressive symptoms, whereas clinically significant anxiety was observed in approximately one-third of the cohort. Psychological distress was not associated with clinical indicators such as eGFR, disease duration, or clinical complexity. However, higher daily medication dosing frequency and female sex emerged as significant predictors of increased anxiety and depressive symptoms. Unexpectedly, healthy controls reported higher levels of depression and trait anxiety than patients. Conclusions Structured multidisciplinary transition programs may help support the emotional well-being of adolescents with CKD, emphasizing the importance of holistic care and the potential benefit of simplifying therapeutic regimens whenever clinically feasible. transition adolescents chronic kidney disease psychological wellbeing comparative design regression models Figures Figure 1 Figure 2 Figure 3 1. Introduction Over the last few decades, advancements in pediatric nephrological care have significantly increased survival rates among adolescents with kidney disorders, including rare and complex forms. Consequently, there is a growing need to ensure continuous and coordinated care as these patients transition into adulthood. This clinical handover occurs during adolescence and young adulthood—an exceptionally delicate phase of life defined by profound physical, psychological, and social changes that are fundamental to the development of personal identity [ 1 ]. Compounding these developmental shifts is the presence of a chronic kidney disease (CKD), which necessitates managing a medical condition that often imposes significant limitations, strict clinical regimens, and a reliance on long-term treatments. Against this backdrop, pathology can interfere with both mental and physical capacities, as well as self-esteem and self-perception, potentially hindering the natural process of individuation and autonomy [ 2 ]. Furthermore, the awareness of the chronicity of the disease and the prospect of undergoing more invasive therapies over time, such as dialysis or kidney transplantation, can elicit profound feelings of fear, anxiety, and frustration [ 3 ]. Therefore, establishing a continuous, consistent, and coordinated process, tailored to the subjective needs of the transitioning adolescent, is essential. Specifically, a robust psychological support framework is fundamental to this process, as it allows monitoring of the patient’s awareness of their condition.[ 4 ] Furthermore, such support facilitates the early identification of specific areas of vulnerability that could potentially compromise the success of the clinical transition. While evidence highlighting the importance of structured transition pathways and the pivotal role of psychological support within pediatric nephrology is steadily accumulating, many clinical centers still lack a formal framework for managing these activities[ 5 ]. In this regard, the present study aims to share the experience of our pediatric nephrology center in implementing a robust and structured transition pathway over the past decade. Moreover, this paper aims to examine the primary mental health indicators in the adolescents and young adults with kidney disease who underwent this transition process, with the objective of identifying potential clinical and demographic predictors of psychological distress. Finally, these indicators were compared with those of a healthy, age- and sex-matched control group to evaluate the relative impact of chronic kidney disease on emotional wellbeing. 2. Materials and Methods 2.1. Study design and settings This study was designed as a cross-sectional, monocentric study conducted at the Pediatric Nephrology and Dialysis Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant’Orsola,Bologna, Italy. 2.2. Participants and Recruitment A total of 93 children and adolescents were enrolled in the study, 60 males and 33 females. Participants were identified and recruited by a transition team between February 2017 and February 2025. Patients were evaluated during their scheduled follow-up outpatient visits. All subjects included in the cohort participated in the structured transition program during the study period. At the time of assessment, their mean age was 17.4 (SD=1.4; range: 14-20). 2.3. The Transition Protocol The transition program implemented at IRCCS Azienda Ospedaliero-Universitaria di Bologna was developed in accordance with the latest evidence-based guidelines[6]. The process is divided into two main stages: the pre-transition phase and the Ppost-transition phase. The pre-transition phase typically begins at age 14 and concludes either when the patient reaches legal adulthood (18 years) or when the transition team deems the patient clinically and psychologically ready for the handover to adult care.This represents the most extensive period of the process, during which the team focuses on the acquisition of Medical-Organizational Competencies ( evaluated asdisease awareness, medication self-management, and appointment scheduling autonomy) and Psychological Competencies ( assessed through clinical interviews and standardized psychological testing). A multidisciplinary team, comprising pediatric nephrologists, adult nephrologists, psychologists, and dieticians, tailors the pathway based on individual patient needs. The transition strategy is primarily dictated by the clinical complexity of the patient’s condition. For this purpose, nephro-urological pathologies were classified into three risk-based categories (see Table 1): 1. Low Complexity : Clinically stable conditions with low risk of progression. These patients are transitioned to Primary Care Physicians (PCPs) with specific follow-up instructions and clear referral criteria for adult nephrology in case of complications. 2. Intermediate Complexity : Conditions with a higher risk of progression requiring direct, continuous specialist follow-up by the adult nephrology unit. 3. High Complexity : Systemic or syndromic diseases necessitating a multidisciplinary team (e.g., specialists in other fields) coordinated by the adult nephrologist. The culmination of this phase is the Joint Transition Visit, where the patient is evaluated simultaneously by both pediatric and adult nephrologists within the pediatric clinic to formally authorize the clinical handover. The post-transition phase is reserved for patients of intermediate or high complexity. Spanning 6 to 12 months after the formal handover, this phase aims to consolidate the new care relationship, reduce the risk of "loss to follow-up," and strengthen the therapeutic alliance with the adult medical team. This stage includes the initial follow-up visit at the adult clinic and a follow-up psychological assessment. 2.4. Psychological Assessment and Tools The psychological assessment follows a structured, three-stage longitudinal protocol, which is personalized to meet the specific needs of each participant. · First Assessment (typically approx. 14 years): The initial clinical interview is conducted with the patient and their family. The primary objectives are to introduce the transition pathway, establish a therapeutic alliance, and identify the specific psychological needs of the adolescents. During this stage, the goals of the long-term intervention are co-defined with the patient. · Second Assessment (typically 16–18 years): It involves the re-administration of a psychometric testing battery to monitor developmental and psychological progress. Notably, the adult nephrology team participates in this session to facilitate the patient’s familiarization with the future adult care environment. · Third Assessment (typically 18–19 years): The final evaluation is held at the adult nephrology unit. Psychometric tools are administered once more to evaluate the overall trajectory of the transition process. This phase focuses on assessing treatment adherence, mental health outcomes, and the perceived efficacy of the multidisciplinary support provided. Depressive and anxiety symptoms were assessed using two self-report questionnaires: · Beck Depression Inventory-II (BDI-II): a 21-item self-report scale assessing the severity of depressive symptoms (e.g., mood, guilt, suicidal ideation) in adolescents and adults. Items are rated on a 4-point Likert scale from 0 to 3, with total scores ranging from 0 to 63. 0–13 indicates minimal depression, 14–19 mild, 20–28 moderate, and 29–63 severe depression. The BDI-II is widely recognized for its high internal consistency (Cronbach’s α 0.9) and reliability (0.73-0.96), demonstrating high sensitivity in detecting changes in depressive symptomatology [7,8]. · State-Trait Anxiety Inventory (STAI): This 40-item inventory distinguishes between State Anxiety (S-Scale), measuring transient emotional responses to specific situations, and Trait Anxiety (T-Scale), evaluating relatively stable individual differences in anxiety proneness. Items are rated on a 4-point Likert scale, with total scores for each scale ranging from 20 to 80. Scores exceeding 40–45 are generally indicative of clinically significant anxiety. The inventory is highly validated, showing excellent internal consistency (Cronbach’s α between 0.86 and 0.95) and strong test-retest reliability [9,10]. 2.5. Data Collection and Ethical Considerations The BDI-II and STAI questionnaires were administered in paper-and-pencil format during the second assessment phase. Clinical data regarding the patients’ underlying nephrological pathology and medical history were extracted directly from the official medical reports generated during the joint transition visit (weight, height, BMI, Schwarz based eGFR [11], serum creatinine (sCr), presence of proteinuria, daily dosing frequency, disease durations, age at diagnosis). To perform comparative analysis, a healthy control group (N = 186) was established. These subjects were recruited from the students attending the University of Padua (Developmental Clinical Psychology Course) coming from all over Italy and were age- and sex-matched to the clinical cohort to minimize confounding variables. Inclusion criteria for the control group were absence of chronic medical conditions, particularly kidney or systemic pathologies; no history of psychiatric disorders or significant psychological distress; no current use of long-term pharmacological treatments. All controls underwent the same psychometric evaluation protocol as the patient group (BDI-II, STAI-S and T) to provide a standardized baseline for comparison. The study protocol was approved by the local Ethics Committee on October 15, 2025 (Ref. code: 379/2025/Oss/AOUBo) and was performed in accordance with the ethical principles of the Declaration of Helsinki. All participants or their legal guardians provided written informed consent prior to enrollment. 2.6. Statistical Analysis Statistical analyses were performed using R Statistical Software (version 2026.01.0, Build 392, R Foundation for Statistical Computing). Continuous variables were treated as normally distributed, supported by the application of the central limit theorem for our sample size and visual inspection of Q-Q plots and density plot. Descriptive statistics are shown as mean and standard deviation for continuous variables, and as absolute frequencies and percentages for categorical data. Outliers were identified through visual inspection of distribution plots. Observations identified as statistical or clinical outliers, those exhibiting values significantly unrepresentative of the study population, were excluded from the final regression models to ensure the stability and robustness of the estimates. To ensure comparability between groups and minimize selection bias, a propensity score matching (nearest neighbor method) was conducted with a 1:2 ratio. Patients and healthy controls were matched based on biological sex and age at the time of evaluation. Differences between the two cohorts were assessed using the independent samples t-test. For comparisons involving clinical complexity grades (Simple, Intermediate, and Complex), One-way Analysis of Variance (ANOVA) was performed, followed by Tukey’s post-hoc test for pairwise comparisons where significant differences were found. Linear regression models were constructed to explore the predictors of psychological distress, specifically evaluating the impact of clinical parameters (such as eGFR, disease duration, and number of daily drug administrations) on BDI-II and STAI scores. Pearson’s correlation coefficient was used to assess the strength of linear relationships between variables. A p-value < 0.05 was considered statistically significant. 3. Results 3.1. Patient Characteristics and Matching Quality A total of 93 patients with pediatric-onset kidney diseases were included in the study cohort. Following the propensity score matching procedure with a 1:2 ratio, 186 healthy individuals were selected as the control group. The cohort consisted of 60 males (64.5%) and 33 females (35.5%). At the time of evaluation, the mean age of the patients was 17.4 ± 1.41 years, with a mean BMI of 22.2 ± 4.07 kg/m^2. Regarding kidney function, the mean sCr was 1.09 ± 0.735 mg/dL, and the mean eGFR was 102 ± 32.8 mL/min/1.73m^2. The mean age at diagnosis was 6.5 ± 5.9 years. Regarding clinical complexity within the patient group (n=93), the cohort was stratified as follows: 17 patients (18%) were classified as simple, 52 (56%) as intermediate, and 24 (26%) as complex, according to the criteria defined in Table 1. Detailed demographic and clinical characteristics of the population are summarized in Table 2. Regarding the distribution of BDI-II scores, 72 patients (77.5%) showed values within the normal range, while 9 (9.7%), 8 (8.6%), and 4 (4.3%) reported mild, moderate, and severe depressive symptoms, respectively. Concerning anxiety levels, 29 patients (31.2%) demonstrated scores above the clinical threshold for STAI-Y1, and 36 patients (38.8%) reported similar elevated values for STAI-Y2. The matching procedure successfully yielded two comparable cohorts. No significant differences were observed between patients and controls regarding age or biological sex distribution (p > 0.05), confirming the balance of the baseline covariates and the effectiveness of the matching process. 3.2. Impact of Clinical Complexity on Anxiety and Depression To investigate whether the severity of the kidney pathology influences the psychological profile, we compared the scores for depressive symptoms and anxiety across the three clinical complexity grades as shown in Table 2. The One-way ANOVA revealed no significant differences in BDI-II scores between the three groups (p = 0.66). Despite the marked differences in kidney function and treatment burden, patients classified as complex reported depressive symptoms comparable to those in the intermediate and simple groups. Similarly, anxiety levels remained remarkably stable across the complexity spectrum. No significant differences were observed for either state anxiety (p = 0.98) or trait anxiety (p = 0.89). 3.3. Clinical and Therapeutic Predictors of Psychological Distress Linear regression analyses were performed to identify which clinical and demographic factors independently contributed to psychological distress within the patient cohort. The daily dosing frequency emerged as the most consistent clinical predictor of psychological wellbeing. Specifically, each additional daily administration was associated with a linear increase in depressive symptoms, resulting in an estimated rise of 0.51 points on the BDI-II scale (β = 0.52, p = 0.017) (BDI-II adjusted R 2 = 0.10, p = 0.007). This trend was even more pronounced regarding anxiety levels. Higher dosing frequency significantly predicted increased STAI-Y1 (β = 0.65, p = 0.020) (STAI-Y1 adjusted R 2 = 0.15, p= 0.0009) and showed its strongest association with STAI-Y2 (β = 0.91, p = 0.002) (STAI-Y2 adjusted R 2 = 0.17; p = 0.0003). In contrast to the impact of the treatment regimen, objective clinical markers of kidney disease showed no significant predictive value for psychological distress. No significant associations (p > 0.05) were found between BDI-II or STAI scores and parameters such as eGFR, sCr, proteinuria, or CKD stage. Furthermore, neither illness duration nor age at diagnosis appeared to influence current levels of depression or anxiety. Finally, biological sex was identified as a powerful demographic predictor of distress. Female patients reported significantly higher scores across all domains, including the BDI-II (β = 5.65. p = 0.001), state anxiety (β = 8.54, p < 0.001), and trait anxiety (β = 8.95, p < 0.001), indicating a specific vulnerability in this subgroup that warrants clinical attention. Notably, a statistically significant difference in psychological scores based on biological sex was also confirmed within the healthy control group (p < 0.05 for all scales). The multivariate models confirmed that both biological sex and daily dosing frequency are robust and independent predictors of distress across all psychological dimensions (Table 3). 3.4. Comparison of Psychological Distress Between Patients and Matched Controls The final stage of the analysis involved comparing the patient cohort (n=93) with the matched healthy control group (n=186) to assess the global impact of kidney disease on psychological wellbeing. Contrary to the initial hypothesis, the healthy control group reported significantly higher levels of depressive symptoms compared to patients (15.71±11.05 vs. 9.69±8.48; F (1,277) = 21.31, p < 0.001). Patients with pediatric-onset kidney disease exhibited lower BDI-II scores compared to the general adolescent and young adult population. The assessment of anxiety symptoms reinforced this inverse trend. For STAI-Y2, healthy controls scored significantly higher than patients (47.16 ±10.80 vs. 41.74±11.56, F (1,277) = 14.89, p < 0.001). (Fig.2) Regarding STAI-Y1, healthy controls again showed a higher mean score (42.33±10.85) compared to patients (39.8±10.93), although this difference showed only a strong trend toward significance (F (1,277) = 3.36, p = 0.067). (Fig.3) 4. Discussion The transition from pediatric to adult care represents a critical period for patients with kidney disorders, often characterized by increased risks of treatment non-adherence and loss in follow-up. The present study aimed to evaluate the psychological symptomatology of adolescents during this delicate phase, yielding several significant findings. In our cohort, the prevalence of clinical depressive symptomatology among adolescent patients with CKD undergoing transition was 22.5%. This finding is consistent with existing literature concerning both pediatric and adult populations, which reports similar indexes in CKD patients [ 12 , 13 ]. Concurrently, the prevalence of anxiety symptoms in this patient group ranged between 31.2% and 38.8%; these values are also in agreement with the rates documented in previous studies, which typically fall within the 30–45% range [ 14 , 15 ]. Contrary to clinical expectations, CKD severity was not significantly associated with anxiety or depression symptoms in our study. Specifically, no correlations emerged regarding age at diagnosis, disease duration, sCr, or eGFR. Even when patients were stratified into simple, intermediate, and complex categories, a classification used in our transition protocol to reflect the cumulative medical burden, psychological scores remained remarkably stable across groups. This lack of statistical significance could suggest that, in adolescents, the clinical severity of the pathology does not directly translate into a proportional psychological burden. In the transition context, a patient with a complex malformation, or a transplant recipient, does not necessarily experience more distress than one with a milder, stable condition. These findings contrast sharply with data from adult populations. In adults, declining eGFR values were clearly correlated with increased depression and suicidal ideation [ 16 ], and dialysis patients reported higher depression symptoms compared with pre-dialysis or transplant recipients [ 17 ]. While recent meta-analytical data [ 12 ] confirm a significant psychological burden across all CKD stages, they highlight that adult patients on kidney replacement therapy, particularly hemodialysis, exhibit the highest vulnerability. However, our results align with the few available pediatric studies, such as those by Kiliś-Pstrusińska et al. [ 14 ] which found no significant differences in reported depression and anxiety symptoms among children on hemodialysis, peritoneal dialysis, or conservative treatment. This discrepancy between age groups may be attributed to the unique developmental stage of adolescence. Patients in this cohort may maintain a different perception of their disease and “patient status" compared to adults. They often lack a comprehensive understanding of the long-term implications of their condition, only recognizing them when functional limitations begin to significantly interfere with daily life [ 1 , 18 ]. Adolescents tend to define "illness" less in terms of laboratory parameters and eGFR and more in terms of how it affects their social life and independence [ 19 ]. In this regard, our study documented a strong correlation between the degree of anxiety and depression and daily dosing frequency. While biological markers failed to reach statistical significance, the number of daily administrations was identified as a robust independent predictor of psychological distress. This "pill burden" specifically appeared to increase trait anxiety, suggesting that the requirement of frequent medication intake acts as a chronic environmental stressor that modulates the patient’s long-term emotional baseline. The literature consistently shows that higher treatment complexity, including frequent dosing, correlates with poorer health-related quality of life and a greater psychiatric symptom burden [ 20 , 21 ]. In pediatric CKD, frequent dosing can exacerbate anxiety and depressive symptoms by increasing caregiver burden and interfering with normal developmental activities [ 22 ]. Managing multiple medication rounds throughout the day serves as a constant, intrusive reminder of the chronic condition of adolescents. Every dose represents a disruption of peer-group activities and school life, reinforcing a "patient identity" at the expense of social normalization. Unlike eGFR or creatinine, biochemical values that the patient may not physically perceive, the dosing schedule is a tangible, daily limitation [ 23 ]. Consequently, our data suggests that simplifying therapeutic regimens and reducing dosing frequency could be a highly effective intervention for improving mental health outcomes during the transition phase. Finally, our analysis identified female gender as a significant risk factor for increased anxiety and depression. This finding aligns with current literature, which consistently reports higher rates of internalizing symptoms among adolescent girls [ 14 , 22 ]. Importantly, in our study, this gender disparity was not limited to the clinical cohort; a similar significant difference was observed within the healthy control group. This suggests that the heightened psychological distress observed in female patients is not a direct consequence of CKD, but rather reflects a broader, age-dependent demographic trend within the adolescent population [ 24 ]. In the clinical setting, however, this pre-existing vulnerability can be exacerbated by the burden of chronic illness. For transition teams, these results emphasize that gender is a more reliable predictor of emotional fragility than kidney function, highlighting the need for gender-tailored psychological screening and support. It is also possibile that females reported higher psychological symptomatology due to gender stereotypes, while males underreported psychological vulnerability to preserve a culturally reinforced image of strength. A final notable finding of our study concerns the comparison between adolescent patients with CKD and their healthy peers. Unexpectedly, our data reveals that patients reported lower scores on both the depression and anxiety scales compared to the control group. This may be explained by the “resilience paradox” in chronic illness, which posits that adolescents facing long-term medical challenges may develop more effective coping mechanisms compared to healthy peers [ 25 ]. This psychological advantage may be attributed to several factors. First, the structured multidisciplinary support provided within a transition program could offer a protective emotional buffer that healthy peers lack. Additionally, the close parental supervision and stronger family bonds often necessitated by CKD treatment may mitigate the social stressors and sense of isolation frequently experienced by healthy adolescents during this turbulent developmental phase [ 26 ]. These findings suggest that, despite the objective burden of the disease, a well-supported transition pathway can effectively safeguard the mental health of adolescent patients [ 27 ]. Several limitations must be acknowledged. First, the cross-sectional design of the study precludes establishing definitive causal relationships between the identified predictors and psychological outcomes. Although daily dosing frequency emerged as a strong predictor of anxiety and depression, only longitudinal studies can confirm whether reducing this burden leads to direct improvements in mental health over time. Second, the study was conducted at a single tertiary care center, which may limit the generalizability of the findings to other transition programs with different multidisciplinary structures or patient populations. In addition, the relatively small sample size of the clinical cohort may have reduced the statistical power to detect subtle differences between subgroups. Third, the psychological assessment relied exclusively on two self-reported questionnaires (BDI-II and STAI). Although these are validated and widely used, they remain susceptible to social desirability bias or the "denial" effect, whereby patients may underreport symptoms to appear more resilient to their clinical team. Finally, while several clinical variables were accounted for, other potential confounders, such as socioeconomic status, parental psychological distress, or school performance, were not included in the analysis and should be addressed in future multi-center prospective studies. 5. Conclusion In conclusion, our findings suggest that the psychological well-being of adolescents transitioning with CKD may be influenced more by female gender and by the practical demands of daily treatment than by the objective clinical severity of the disease itself. While parameters such as eGFR and disease duration remain essential for medical management, they did not appear to constitute risk factors for anxiety or depression symptoms in our cohort. Instead, daily dosing frequency emerged as a significant factor associated with psychological distress, suggesting that the "pill burden" may act as a tangible daily stressor for these patients. The observation of a potential “paradox”, in which patients reported lower distress levels than their healthy peers, may reflect the protective effects of structured multidisciplinary support, close parental supervision and stronger family bonds. However, these results should be interpreted with caution given the limitations of our study. Ultimately, these insights underscore the value of a holistic approach to the transition process. While further research is needed to confirm these trends, our data suggest that simplifying therapeutic regimens, when clinically feasible, could be a modest but meaningful step toward supporting the emotional well-being of adolescents as they progress to adult care. Declarations Author Contributions Conceptualization, D.S.; methodology, D.S. and M.T.; formal analysis, M.T. and P.C.; investigation, D.S. and M.T.; data curation, M.T. and D.S.; writing—original draft preparation, P.C..; writing—review and editing, A.P., M.T. and D.S.; project administration, D.S. All authors have read and agreed to the published version of the manuscript. Funding This research received no external funding. Institutional Review Board Statement The study was conducted in accordance with the Declaration of Helsinki, and approved by the local Ethics Committee on October 15, 2025 (Ref. code: 379/2025/Oss/AOUBo) Informed Consent Statement Informed consent was obtained from all subjects involved in the study. Data Availability Statement The research data have been submitted as supplementary material. Conflicts of Interest The authors declare no conflicts of interest. Acknowledgments The authors would like to express their sincere gratitude to Maria Chiara Tullini for their invaluable support and dedication to the clinical activities throughout this study. References Dallimore, D.J.; Neukirchinger, B.; Noyes, J. Why Is Transition between Child and Adult Services a Dangerous Time for Young People with Chronic Kidney Disease? A Mixed-Method Systematic Review. PLOS ONE 2018 , 13 , e0201098, doi:10.1371/journal.pone.0201098. Drohan, C.; van Zwieten, A.; Mallitt, K.-A.; Durkan, A.; Hahn, D.; Guha, C.; Khalid, R.; Lorenzo, J.; Lah, S.; Didsbury, M.; et al. Emotional, Behavioural and Adaptive Function in Children with Chronic Kidney Disease: The Kids with CKD (KCAD) Study. Pediatr Nephrol 2025 , doi:10.1007/s00467-025-07091-8. Blum, R.W.; Garell, D.; Hodgman, C.H.; Jorissen, W.; Okinow, N.A.W.; Orr, D.P.; Slap, G.B. Transition from Child Centered Systems for Adolescents with Chronic Conditions. Journal of Adolescent Health 1993 , 14 , 570–576. Mai, K.; Dawson, A.E.; Gu, L.; LaMotte, J.E.; Molitor, S.; Zimmerman, C.T. Common Mental Health Conditions and Considerations in Pediatric Chronic Kidney Disease. Pediatr Nephrol 2024 , 39 , 2887–2897, doi:10.1007/s00467-024-06314-8. Perez Gomez, M.V.; Costea, G.-C.; Claus, L.; Cornec-Le Gall, E.; van Eerde, A.M.; Lemoine, S.; Groothoff, J.; Levtchenko, E.; Klein, L.; Pape, L.; et al. Transition of Patients with Hereditary Nephropathies from Paediatric to Adult Care. Nephrol Dial Transplant 2026 , 41 , 367–379, doi:10.1093/ndt/gfaf186. White PH, Cooley WC; Transitions Clinical Report Authoring Group; American Academy of Pediatrics; American Academy of Family Physicians; American College of Physicians. Supporting the Health Care Transition From Adolescence to Adulthood in the Medical Home. Pediatrics. 2018;142(5):E20182587. Pediatrics 2019 , 143 , e20183610, doi:10.1542/peds.2018-3610. Rosner, R.I. Beck Depression Inventory (BDI). In The Encyclopedia of Clinical Psychology ; John Wiley & Sons, Ltd, 2015; pp. 1–6 ISBN 978-1-118-62539-2. Wang, Y.-P.; Gorenstein, C. Psychometric Properties of the Beck Depression Inventory-II: A Comprehensive Review. Braz J Psychiatry 2013 , 35 , 416–431, doi:10.1590/1516-4446-2012-1048. Skapinakis, P. Spielberger State-Trait Anxiety Inventory. In Encyclopedia of Quality of Life and Well-Being Research ; Michalos, A.C., Ed.; Springer Netherlands: Dordrecht, 2014; pp. 6261–6264 ISBN 978-94-007-0753-5. Ortuño-Sierra, J.; García-Velasco, L.; Inchausti, F.; Debbané, M.; Fonseca-Pedrero, E. New Approaches on the Study of the Psychometric Properties of the STAI. Actas Esp Psiquiatr 2016 , 44 , 83–92. Schwartz, G.J.; Mun[Combining Tilde]oz, A.; Schneider, M.F.; Mak, R.H.; Kaskel, F.; Warady, B.A.; Furth, S.L. New Equations to Estimate GFR in Children with CKD. Journal of the American Society of Nephrology 2009 , 20 , 629, doi:10.1681/ASN.2008030287. Adejumo, O.A.; Edeki, I.R.; Sunday Oyedepo, D.; Falade, J.; Yisau, O.E.; Ige, O.O.; Adesida, A.O.; Daniel Palencia, H.; Sabri Moussa, A.; Abdulmalik, J.; et al. Global Prevalence of Depression in Chronic Kidney Disease: A Systematic Review and Meta-Analysis. J Nephrol 2024 , 37 , 2455–2472, doi:10.1007/s40620-024-01998-5. Kogon, A.J.; Stoep, A.V.; Weiss, N.S.; Smith, J.; Flynn, J.T.; McCauley, E. Depression and Its Associated Factors in Pediatric Chronic Kidney Disease. Pediatr Nephrol 2013 , 28 , 1855–1861, doi:10.1007/s00467-013-2497-5. Kiliś-Pstrusińska, K.; Medyńska, A.; Adamczyk, P.; Leszczyńska, B.; Szczepańska, M.; Tkaczyk, M.; Wasilewska, A.M.; Zachwieja, K.; Zagożdżon, I.; Kujawa, K.; et al. Depressive Disorders in Children with Chronic Kidney Disease Treated Conservatively. Adv Clin Exp Med 2024 , 33 , 1189–1199, doi:10.17219/acem/175236. Huang, C.W.; Wee, P.H.; Low, L.L.; Koong, Y.L.A.; Htay, H.; Fan, Q.; Foo, W.Y.M.; Seng, J.J.B. Prevalence and Risk Factors for Elevated Anxiety Symptoms and Anxiety Disorders in Chronic Kidney Disease: A Systematic Review and Meta-Analysis. General Hospital Psychiatry 2021 , 69 , 27–40, doi:10.1016/j.genhosppsych.2020.12.003. Jhee, J.H.; Lee, E.; Cha, M.-U.; Lee, M.; Kim, H.; Park, S.; Yun, H.-R.; Jung, S.-Y.; Kee, Y.K.; Yoon, C.-Y.; et al. Prevalence of Depression and Suicidal Ideation Increases Proportionally with Renal Function Decline, Beginning from Early Stages of Chronic Kidney Disease. Medicine (Baltimore) 2017 , 96 , e8476, doi:10.1097/MD.0000000000008476. Dziubek, W.; Pawlaczyk, W.; Rogowski, L.; Stefanska, M.; Golebiowski, T.; Mazanowska, O.; Krajewska, M.; Kusztal, M.; Kowalska, J. Assessment of Depression and Anxiety in Patients with Chronic Kidney Disease and after Kidney Transplantation-A Comparative Analysis. Int J Environ Res Public Health 2021 , 18 , 10517, doi:10.3390/ijerph181910517. Crawford, K.; Wilson, C.; Low, J.K.; Manias, E.; Williams, A. Transitioning Adolescents to Adult Nephrology Care: A Systematic Review of the Experiences of Adolescents, Parents, and Health Professionals. Pediatr Nephrol 2020 , 35 , 555–567, doi:10.1007/s00467-019-04223-9. Pinquart, M.; Shen, Y. Depressive Symptoms in Children and Adolescents with Chronic Physical Illness: An Updated Meta-Analysis. J Pediatr Psychol 2011 , 36 , 375–384, doi:10.1093/jpepsy/jsq104. Alshelleh, S.; Alhouri, A.; Taifour, A.; Abu-Hussein, B.; Alwreikat, F.; Abdelghani, M.; Badran, M.; Al-Asa’d, Y.; Alhawari, H.; Oweis, A.O. Prevelance of Depression and Anxiety with Their Effect on Quality of Life in Chronic Kidney Disease Patients. Sci Rep 2022 , 12 , 17627, doi:10.1038/s41598-022-21873-2. Díaz-González de Ferris, M.E.; Pierce, C.B.; Gipson, D.S.; Furth, S.L.; Warady, B.A.; Hooper, S.R. Health-Related Quality of Life in Children with Chronic Kidney Disease Is Affected by the Number of Medications. Pediatr Nephrol 2021 , 36 , 1307–1310, doi:10.1007/s00467-021-04919-x. Mai, K.; Dawson, A.E.; Gu, L.; LaMotte, J.E.; Molitor, S.; Zimmerman, C.T. Common Mental Health Conditions and Considerations in Pediatric Chronic Kidney Disease. Pediatr Nephrol 2024 , 39 , 2887–2897, doi:10.1007/s00467-024-06314-8. Zelikovsky, N.; Nelson, E. Illness Perceptions and Beliefs about Medication: Impact on Health-Related Quality of Life in Adolescent Kidney Transplant Recipients. Pediatric Transplantation 2021 , 25 , e13988, doi:10.1111/petr.13988. Anderson, T.L.; Valiauga, R.; Tallo, C.; Hong, C.B.; Manoranjithan, S.; Domingo, C.; Paudel, M.; Untaroiu, A.; Barr, S.; Goldhaber, K. Contributing Factors to the Rise in Adolescent Anxiety and Associated Mental Health Disorders: A Narrative Review of Current Literature. Journal of Child and Adolescent Psychiatric Nursing 2025 , 38 , e70009, doi:10.1111/jcap.70009. Moreira, J.M.; Bouissou Morais Soares, C.M.; Teixeira, A.L.; Simões e Silva, A.C.; Kummer, A.M. Anxiety, Depression, Resilience and Quality of Life in Children and Adolescents with Pre-Dialysis Chronic Kidney Disease. Pediatr Nephrol 2015 , 30 , 2153–2162, doi:10.1007/s00467-015-3159-6. Pruette, C.S.; Ranch, D.; Shih, W.V.; Ferris, M.D.-G. Health Care Transition in Adolescents and Young Adults With Chronic Kidney Disease: Focus on the Individual and Family Support Systems. Advances in Chronic Kidney Disease 2022 , 29 , 318–326, doi:10.1053/j.ackd.2022.02.004. Sawyer, S.M.; Drew, S.; Yeo, M.S.; Britto, M.T. Adolescents with a Chronic Condition: Challenges Living, Challenges Treating. The Lancet 2007 , 369 , 1481–1489, doi:10.1016/S0140-6736(07)60370-5. Tables Table 1. Clinical Complexity Classification of Pediatric-Onset Kidney Diseases Clinical Complexity Low Complexity Intermediate Complexity High Complexity Transition Care Setting Primary Care Physician (General Practitioner) Adult Nephrologist Adult Nephrologist and Multidisciplinary Team Clinical Conditions • Stage I CKD due to CAKUT (e.g., solitary kidney, hypoplastic kidney, low-to-moderate grade VUR, mild urinary tract dilation) • Follow-up for previous AKI (e.g., uncomplicated typical HUS) • Uncomplicated Calcium Oxalate Nephrolithiasis • Nephrotic Syndrome in remission for >2 years • Recurrent simple Urinary Tract Infections (UTIs) • Enuresis and voiding disorders (without increased bladder pressure) • Stage II and III CKD • CAKUT with proteinuria and/or hypertension • Follow-up for previous AKI with sequelae • Chronic Glomerulonephritis (GN) • GN secondary to vasculitis • Frequent relapsing or steroid-dependent Nephrotic Syndrome • Alport Syndrome • Uncomplicated ADPKD • Recurrent and/or complicated Nephrolithiasis • Stage IV and V CKD, or ESRD (Dialysis) • Kidney Transplantation • Complex Nephro-uropathies requiring urological follow-up (e.g., PUV and others) • Atypical HUS • Tubulopathies • Ciliopathies (non-ADPKD) • Nephrolithiasis due to metabolic diseases • Metabolic diseases with renal expression (e.g., Cystinosis) • Chronic GN with Renal Insufficiency (RI) • Steroid- or multi-drug resistant Nephrotic Syndrome • Nephropathies associated with syndromes or disabilities Table 2. Demographic, clinical, and psychological characteristics of patients stratified by clinical complexity Variable Simple Intermediate Complex Total p-value Patients, n (%) 17 (18.2) 51 (54.8) 25 (26.9) 93 Demographics Sex (Male), n (%) 13 (76.4) 32 (61.3) 15 (60) 60 (64.5) Weight (Kg), Mean ± SD 69.2±19.6 65.9±15.9 51.0±14.8 62.3±17.6 Height (cm), Mean ± SD 172.6±11.4 169.5±10.6 161.4±9.5 167.0±10.9 BMI (kg/m^2), Mean ± SD 23.1±5.7 22.6±4.1 20.75±2.27 22.2±4.1 0.11 Clinical Parameters Age at Diagnosis (years), Mean ± SD 3.9±5.5 7.8±6.1 5.7±5.3 6.5±5.9 <0.05 Time at Diagnosis (years), Mean ± SD 14.0±6.1 9.8±6.4 12.6±5.8 11.3±6.4 0.06 Serum Creatinine (mg/dL), Mean ± SD 0.8±0.1 0.9±0.4 1.6±1.1 1.1±0.7 <0.001 eGFR (mL/min/1.73m^2) 111.9±15.9 112.63±28.5 87.1±71.3 102±32.8 <0.05 CKD stage, n (%) 1 2 3 4 5 16 (94.1) 1 (5.9) 0 0 0 40 (78.4) 8 (15.7) 3 (5.9) 0 0 8 (32) 8 (32) 5 (20) 4 (16) 0 64 (68.8) 17 (18.3) 8 (8.6) 4 (4.3) 0 <0.001 Proteinuria, n (%) 2 (11.8) 15 (29.4) 8 (32.0) 25 (26.9) 0.5 Daily dosing frequency, Mean ± SD 0.4±0.7 1.5±1.5 3.8±2.4 1.8±2.0 <0.001 Psychological Assessment Time at Test (years), Mean ± SD 17.7±1.6 17.3±1.4 17.2±1.2 17.4±1.4 0.54 BDI-II, Mean ± SD 10.8±6.48 9.0±7.9 10.4±10.7 9.7±8.5 0.66 STAI-Y , Mean ± SD 39.3±10.3 39.9±10.1 40.0±13.3 39.8±10.9 0.98 STAI-Y2 , Mean ± SD 42.7±11.9 41.2±10.5 42.1±13.6 41.7±11.6 0.89 Table 3. Univariate and Multivariate Linear Regression Analysis of Predictors for Depressive Symptoms (BDI-II), State Anxiety (STAI-Y1), and Trait Anxiety (STAI-Y2). Predictor Variable β (Unweighted) Std. Error t Univariate p Multivariate p BDI-II Daily dosing frequency 0.52 0.21 2.42 0.017 0.05 Sex (Female) 5.65 1.75 3.23 0.002 0.02 Age at Diagnosis -0.003 0.01 -0.23 0.820 — Disease Duration -0.001 0.01 -0.11 0.916 — eGFR 0.01 0.02 0.28 0.778 0.98 BMI -0.02 0.22 -0.07 0.940 — STAI-Y1 Daily dosing frequency 0.65 0.28 2.36 0.020 0.1 Sex (Female) 8.54 2.21 3.87 < 0.001 0.002 Age at Diagnosis 0.004 0.02 0.27 0.787 — Disease Duration -0.007 0.01 -0.47 0.641 — eGFR -0.02 0.03 -0.83 0.407 0.17 BMI -0.02 0.29 -0.07 0.945 — STAI-Y2 Daily dosing frequency 0.91 0.29 3.18 0.002 0.009 Sex (Female) 8.95 2.34 3.83 < 0.001 0.006 Age at Diagnosis -0.007 0.02 -0.41 0.681 — Disease Duration 0.005 0.02 0.34 0.735 — eGFR 0.01 0.03 0.53 0.599 0.83 BMI -0.49 0.30 -1.63 0.106 — (BDI-II Adjusted R 2 = 0.10, p = 0.0007; STAI-Y1 Adjusted R 2 = 0.15, p = 0.0009; STAI-Y2 Adjusted R 2 = 0.17, p = 0.0003) Supplementary Files GraphicalAbstract.pptx finaldatabase.xlsx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Major Revisions Needed 01 May, 2026 Reviewers agreed at journal 08 Apr, 2026 Reviewers invited by journal 08 Apr, 2026 Editor assigned by journal 07 Apr, 2026 First submitted to journal 31 Mar, 2026 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9284328","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":619822688,"identity":"4c957d52-6a7e-47a0-93c8-e97e5b9cea0f","order_by":0,"name":"Dorella Scarponi","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S Orsola: IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola","correspondingAuthor":false,"prefix":"","firstName":"Dorella","middleName":"","lastName":"Scarponi","suffix":""},{"id":619822689,"identity":"bca78382-dbcc-4da6-9989-0e56e32f2bda","order_by":1,"name":"Marta Tremolada","email":"","orcid":"","institution":"Università degli Studi di Padova Dipartimento di Psicologia dello Sviluppo e della Socializzazione: Universita degli Studi di Padova Dipartimento di Psicologia dello Sviluppo e della Socializzazione","correspondingAuthor":false,"prefix":"","firstName":"Marta","middleName":"","lastName":"Tremolada","suffix":""},{"id":619822690,"identity":"7d86410f-51d5-4716-a1b3-95229c9ab657","order_by":2,"name":"Pasquale Castaldo","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0006-8860-5590","institution":"University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic: IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola","correspondingAuthor":true,"prefix":"","firstName":"Pasquale","middleName":"","lastName":"Castaldo","suffix":""},{"id":619822691,"identity":"ec3228b2-d5ac-4806-90f7-5a99f9661d54","order_by":3,"name":"Roberto Pillon","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S Orsola: IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola","correspondingAuthor":false,"prefix":"","firstName":"Roberto","middleName":"","lastName":"Pillon","suffix":""},{"id":619822692,"identity":"0eb71658-29c4-4e0b-bc87-982af940ea70","order_by":4,"name":"Thomas Ria","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S Orsola: IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Ria","suffix":""},{"id":619822693,"identity":"0c0e2b86-5a8b-4bf4-a3fc-bb4074259f9b","order_by":5,"name":"Andrea Pasini","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S Orsola: IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico di Sant'Orsola","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Pasini","suffix":""}],"badges":[],"createdAt":"2026-03-31 21:09:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9284328/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9284328/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107245360,"identity":"3b0e1eef-afb3-4f1c-9238-b1c43f1ff70d","added_by":"auto","created_at":"2026-04-19 08:05:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":7048517,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of Depressive Symptoms (BDI-II) scores between patients and matched healthy controls.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9284328/v1/42a09443f41f486653f9aef8.png"},{"id":107484548,"identity":"b29bf168-0907-4108-aeb6-b114aeba53b5","added_by":"auto","created_at":"2026-04-22 02:32:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":13741000,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of Trait Anxiety (STAI-Y2) scores between patients and matched healthy controls.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9284328/v1/dd246973b237345b44fc624f.png"},{"id":107245363,"identity":"e2822731-c2a5-4fcd-ab11-8689ed513a1a","added_by":"auto","created_at":"2026-04-19 08:05:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":13731631,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of State Anxiety (STAI-Y1) scores between patients and matched healthy controls.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9284328/v1/052474ea59ecbebd3eb9fd10.png"},{"id":107484517,"identity":"501df67d-1477-425a-9fbf-9cb56d49a41b","added_by":"auto","created_at":"2026-04-22 02:32:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":21001461,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9284328/v1/ca45622b-6e13-4633-b0c6-12c4b6f190e5.pdf"},{"id":107245364,"identity":"a6aa8374-5448-4a7d-9c5b-21c83b1cb1d7","added_by":"auto","created_at":"2026-04-19 08:05:01","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":178244,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.pptx","url":"https://assets-eu.researchsquare.com/files/rs-9284328/v1/da388c7f7652c92c4db082a4.pptx"},{"id":107245362,"identity":"5bf72fd3-5316-4cb8-9478-0d63a735253a","added_by":"auto","created_at":"2026-04-19 08:05:01","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":38512448,"visible":true,"origin":"","legend":"","description":"","filename":"finaldatabase.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-9284328/v1/40a8a9ae99053ce711bba03c.xlsx"}],"financialInterests":"","formattedTitle":"Anxiety And Depression Symptomatology In Adolescents With Kidney Disorders During Pediatric-To-Adult Transition: “Perception Of Illness” And The “Patient Paradox”","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOver the last few decades, advancements in pediatric nephrological care have significantly increased survival rates among adolescents with kidney disorders, including rare and complex forms. Consequently, there is a growing need to ensure continuous and coordinated care as these patients transition into adulthood. This clinical handover occurs during adolescence and young adulthood\u0026mdash;an exceptionally delicate phase of life defined by profound physical, psychological, and social changes that are fundamental to the development of personal identity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCompounding these developmental shifts is the presence of a chronic kidney disease (CKD), which necessitates managing a medical condition that often imposes significant limitations, strict clinical regimens, and a reliance on long-term treatments. Against this backdrop, pathology can interfere with both mental and physical capacities, as well as self-esteem and self-perception, potentially hindering the natural process of individuation and autonomy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Furthermore, the awareness of the chronicity of the disease and the prospect of undergoing more invasive therapies over time, such as dialysis or kidney transplantation, can elicit profound feelings of fear, anxiety, and frustration [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherefore, establishing a continuous, consistent, and coordinated process, tailored to the subjective needs of the transitioning adolescent, is essential. Specifically, a robust psychological support framework is fundamental to this process, as it allows monitoring of the patient\u0026rsquo;s awareness of their condition.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Furthermore, such support facilitates the early identification of specific areas of vulnerability that could potentially compromise the success of the clinical transition. While evidence highlighting the importance of structured transition pathways and the pivotal role of psychological support within pediatric nephrology is steadily accumulating, many clinical centers still lack a formal framework for managing these activities[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this regard, the present study aims to share the experience of our pediatric nephrology center in implementing a robust and structured transition pathway over the past decade. Moreover, this paper aims to examine the primary mental health indicators in the adolescents and young adults with kidney disease who underwent this transition process, with the objective of identifying potential clinical and demographic predictors of psychological distress. Finally, these indicators were compared with those of a healthy, age- and sex-matched control group to evaluate the relative impact of chronic kidney disease on emotional wellbeing.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1. Study design and settings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was designed as a cross-sectional, monocentric study conducted at the Pediatric Nephrology and Dialysis Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant\u0026rsquo;Orsola,Bologna, Italy. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2. Participants and Recruitment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 93 children and adolescents were enrolled in the study, 60 males and 33 females. Participants were identified and recruited by a transition team between February 2017 and February 2025. Patients were evaluated during their scheduled follow-up outpatient visits. All subjects included in the cohort participated in the structured transition program during the study period. At the time of assessment, their mean age was 17.4 (SD=1.4; range: 14-20).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3. \u003c/strong\u003e\u003cstrong\u003eThe Transition Protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe transition program implemented at IRCCS Azienda Ospedaliero-Universitaria di Bologna was developed in accordance with the latest evidence-based guidelines[6]. The process is divided into two main stages: the pre-transition phase and the Ppost-transition phase. \u003c/p\u003e\n\u003cp\u003eThe \u003cstrong\u003epre-transition phase\u003c/strong\u003e typically begins at age 14 and concludes either when the patient reaches legal adulthood (18 years) or when the transition team deems the patient clinically and psychologically ready for the handover to adult care.This represents the most extensive period of the process, during which the team focuses on the acquisition of Medical-Organizational Competencies\u003cstrong\u003e (\u003c/strong\u003eevaluated asdisease awareness, medication self-management, and appointment scheduling autonomy) and Psychological Competencies\u003cstrong\u003e (\u003c/strong\u003eassessed through clinical interviews and standardized psychological testing).\u003c/p\u003e\n\u003cp\u003eA multidisciplinary team, comprising pediatric nephrologists, adult nephrologists, psychologists, and dieticians, tailors the pathway based on individual patient needs. The transition strategy is primarily dictated by the clinical complexity of the patient\u0026rsquo;s condition. For this purpose, nephro-urological pathologies were classified into three risk-based categories (see Table 1):\u003c/p\u003e\n\u003cp\u003e1. \u003cstrong\u003eLow Complexity\u003c/strong\u003e: Clinically stable conditions with low risk of progression. These patients are transitioned to Primary Care Physicians (PCPs) with specific follow-up instructions and clear referral criteria for adult nephrology in case of complications.\u003c/p\u003e\n\u003cp\u003e2. \u003cstrong\u003eIntermediate Complexity\u003c/strong\u003e: Conditions with a higher risk of progression requiring direct, continuous specialist follow-up by the adult nephrology unit.\u003c/p\u003e\n\u003cp\u003e3. \u003cstrong\u003eHigh Complexity\u003c/strong\u003e: Systemic or syndromic diseases necessitating a multidisciplinary team (e.g., specialists in other fields) coordinated by the adult nephrologist.\u003c/p\u003e\n\u003cp\u003eThe culmination of this phase is the Joint Transition Visit, where the patient is evaluated simultaneously by both pediatric and adult nephrologists within the pediatric clinic to formally authorize the clinical handover.\u003c/p\u003e\n\u003cp\u003eThe \u003cstrong\u003epost-transition phase\u003c/strong\u003e is reserved for patients of intermediate or high complexity. Spanning 6 to 12 months after the formal handover, this phase aims to consolidate the new care relationship, reduce the risk of \u0026quot;loss to follow-up,\u0026quot; and strengthen the therapeutic alliance with the adult medical team. This stage includes the initial follow-up visit at the adult clinic and a follow-up psychological assessment.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e2.4. \u003c/strong\u003e\u003cstrong\u003ePsychological Assessment and Tools\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe psychological assessment follows a structured, three-stage longitudinal protocol, which is personalized to meet the specific needs of each participant.\u003c/p\u003e\n\u003cp\u003e\u0026middot; \u003cstrong\u003eFirst Assessment (typically approx. 14 years):\u003c/strong\u003e The initial clinical interview is conducted with the patient and their family. The primary objectives are to introduce the transition pathway, establish a therapeutic alliance, and identify the specific psychological needs of the adolescents. During this stage, the goals of the long-term intervention are co-defined with the patient.\u003c/p\u003e\n\u003cp\u003e\u0026middot; \u003cstrong\u003eSecond Assessment (typically 16\u0026ndash;18 years): \u003c/strong\u003eIt involves the re-administration of a psychometric testing battery to monitor developmental and psychological progress. Notably, the adult nephrology team participates in this session to facilitate the patient\u0026rsquo;s familiarization with the future adult care environment.\u003c/p\u003e\n\u003cp\u003e\u0026middot; \u003cstrong\u003eThird Assessment (typically 18\u0026ndash;19 years):\u003c/strong\u003e The final evaluation is held at the adult nephrology unit. Psychometric tools are administered once more to evaluate the overall trajectory of the transition process. This phase focuses on assessing treatment adherence, mental health outcomes, and the perceived efficacy of the multidisciplinary support provided.\u003c/p\u003e\n\u003cp\u003eDepressive and anxiety symptoms were assessed using two self-report questionnaires:\u003c/p\u003e\n\u003cp\u003e\u0026middot; \u003cstrong\u003eBeck Depression Inventory-II (BDI-II):\u003c/strong\u003e a 21-item self-report scale assessing the severity of depressive symptoms (e.g., mood, guilt, suicidal ideation) in adolescents and adults. Items are rated on a 4-point Likert scale from 0 to 3, with total scores ranging from 0 to 63. 0\u0026ndash;13 indicates minimal depression, 14\u0026ndash;19 mild, 20\u0026ndash;28 moderate, and 29\u0026ndash;63 severe depression. The BDI-II is widely recognized for its high internal consistency (Cronbach\u0026rsquo;s \u0026alpha; 0.9) and reliability (0.73-0.96), demonstrating high sensitivity in detecting changes in depressive symptomatology [7,8].\u003c/p\u003e\n\u003cp\u003e\u0026middot; \u003cstrong\u003eState-Trait Anxiety Inventory (STAI):\u003c/strong\u003e This 40-item inventory distinguishes between State Anxiety (S-Scale), measuring transient emotional responses to specific situations, and Trait Anxiety (T-Scale), evaluating relatively stable individual differences in anxiety proneness. Items are rated on a 4-point Likert scale, with total scores for each scale ranging from 20 to 80. Scores exceeding 40\u0026ndash;45 are generally indicative of clinically significant anxiety. The inventory is highly validated, showing excellent internal consistency (Cronbach\u0026rsquo;s \u0026alpha; between 0.86 and 0.95) and strong test-retest reliability [9,10].\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003e2.5. \u003c/strong\u003e\u003cstrong\u003eData Collection and Ethical Considerations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe BDI-II and STAI questionnaires were administered in paper-and-pencil format during the second assessment phase. Clinical data regarding the patients\u0026rsquo; underlying nephrological pathology and medical history were extracted directly from the official medical reports generated during the joint transition visit (weight, height, BMI, Schwarz based eGFR [11], serum creatinine (sCr), presence of proteinuria, daily dosing frequency, disease durations, age at diagnosis).\u003c/p\u003e\n\u003cp\u003eTo perform comparative analysis, a healthy control group (N = 186) was established. These subjects were recruited from the students attending the University of Padua (Developmental Clinical Psychology Course) coming from all over Italy and were age- and sex-matched to the clinical cohort to minimize confounding variables. Inclusion criteria for the control group were absence of chronic medical conditions, particularly kidney or systemic pathologies; no history of psychiatric disorders or significant psychological distress; no current use of long-term pharmacological treatments. All controls underwent the same psychometric evaluation protocol as the patient group (BDI-II, STAI-S and T) to provide a standardized baseline for comparison.\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the local Ethics Committee on October 15, 2025 (Ref. code: 379/2025/Oss/AOUBo) and was performed in accordance with the ethical principles of the Declaration of Helsinki. All participants or their legal guardians provided written informed consent prior to enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.6. \u003c/strong\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using R Statistical Software (version 2026.01.0, Build 392, R Foundation for Statistical Computing). Continuous variables were treated as normally distributed, supported by the application of the central limit theorem for our sample size and visual inspection of Q-Q plots and density plot. Descriptive statistics are shown as mean and standard deviation for continuous variables, and as absolute frequencies and percentages for categorical data.\u003c/p\u003e\n\u003cp\u003eOutliers were identified through visual inspection of distribution plots. Observations identified as statistical or clinical outliers, those exhibiting values significantly unrepresentative of the study population, were excluded from the final regression models to ensure the stability and robustness of the estimates.\u003c/p\u003e\n\u003cp\u003eTo ensure comparability between groups and minimize selection bias, a propensity score matching (nearest neighbor method) was conducted with a 1:2 ratio. Patients and healthy controls were matched based on biological sex and age at the time of evaluation. Differences between the two cohorts were assessed using the independent samples t-test. For comparisons involving clinical complexity grades (Simple, Intermediate, and Complex), One-way Analysis of Variance (ANOVA) was performed, followed by Tukey\u0026rsquo;s post-hoc test for pairwise comparisons where significant differences were found.\u003c/p\u003e\n\u003cp\u003eLinear regression models were constructed to explore the predictors of psychological distress, specifically evaluating the impact of clinical parameters (such as eGFR, disease duration, and number of daily drug administrations) on BDI-II and STAI scores. Pearson\u0026rsquo;s correlation coefficient was used to assess the strength of linear relationships between variables. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1. Patient Characteristics and Matching Quality\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 93 patients with pediatric-onset kidney diseases were included in the study cohort. Following the propensity score matching procedure with a 1:2 ratio, 186 healthy individuals were selected as the control group.\u003c/p\u003e\n\u003cp\u003eThe cohort consisted of 60 males (64.5%) and 33 females (35.5%). At the time of evaluation, the mean age of the patients was 17.4 ± 1.41 years, with a mean BMI of 22.2 ± 4.07 kg/m^2. Regarding kidney function, the mean sCr was 1.09 ± 0.735 mg/dL, and the mean eGFR was 102 ± 32.8 mL/min/1.73m^2. The mean age at diagnosis was 6.5 ± 5.9 years. Regarding clinical complexity within the patient group (n=93), the cohort was stratified as follows: 17 patients (18%) were classified as simple, 52 (56%) as intermediate, and 24 (26%) as complex, according to the criteria defined in Table 1. Detailed demographic and clinical characteristics of the population are summarized in Table 2.\u003c/p\u003e\n\u003cp\u003eRegarding the distribution of BDI-II scores, 72 patients (77.5%) showed values within the normal range, while 9 (9.7%), 8 (8.6%), and 4 (4.3%) reported mild, moderate, and severe depressive symptoms, respectively. Concerning anxiety levels, 29 patients (31.2%) demonstrated scores above the clinical threshold for STAI-Y1, and 36 patients (38.8%) reported similar elevated values for STAI-Y2.\u003c/p\u003e\n\u003cp\u003eThe matching procedure successfully yielded two comparable cohorts. No significant differences were observed between patients and controls regarding age or biological sex distribution (p \u0026gt; 0.05), confirming the balance of the baseline covariates and the effectiveness of the matching process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2. Impact of Clinical Complexity on Anxiety and Depression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo investigate whether the severity of the kidney pathology influences the psychological profile, we compared the scores for depressive symptoms and anxiety across the three clinical complexity grades as shown in Table 2.\u003c/p\u003e\n\u003cp\u003eThe One-way ANOVA revealed no significant differences in BDI-II scores between the three groups (p = 0.66). Despite the marked differences in kidney function and treatment burden, patients classified as complex reported depressive symptoms comparable to those in the intermediate and simple groups. Similarly, anxiety levels remained remarkably stable across the complexity spectrum. No significant differences were observed for either state anxiety (p = 0.98) or trait anxiety (p = 0.89).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3. \u003c/strong\u003e\u003cstrong\u003e Clinical and Therapeutic Predictors of Psychological Distress\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLinear regression analyses were performed to identify which clinical and demographic factors independently contributed to psychological distress within the patient cohort. \u003c/p\u003e\n\u003cp\u003eThe daily dosing frequency emerged as the most consistent clinical predictor of psychological wellbeing. Specifically, each additional daily administration was associated with a linear increase in depressive symptoms, resulting in an estimated rise of 0.51 points on the BDI-II scale (β = 0.52, p = 0.017) (BDI-II adjusted R\u003csup\u003e2\u003c/sup\u003e = 0.10, p = 0.007). This trend was even more pronounced regarding anxiety levels. Higher dosing frequency significantly predicted increased STAI-Y1 (β = 0.65, p = 0.020) (STAI-Y1 adjusted R\u003csup\u003e2\u003c/sup\u003e = 0.15, p= 0.0009) and showed its strongest association with STAI-Y2 (β = 0.91, p = 0.002) (STAI-Y2 adjusted R\u003csup\u003e2\u003c/sup\u003e = 0.17; p = 0.0003).\u003c/p\u003e\n\u003cp\u003eIn contrast to the impact of the treatment regimen, objective clinical markers of kidney disease showed no significant predictive value for psychological distress. No significant associations (p \u0026gt; 0.05) were found between BDI-II or STAI scores and parameters such as eGFR, sCr, proteinuria, or CKD stage. Furthermore, neither illness duration nor age at diagnosis appeared to influence current levels of depression or anxiety. \u003c/p\u003e\n\u003cp\u003eFinally, biological sex was identified as a powerful demographic predictor of distress. Female patients reported significantly higher scores across all domains, including the BDI-II (β = 5.65. p = 0.001), state anxiety (β = 8.54, p \u0026lt; 0.001), and trait anxiety (β = 8.95, p \u0026lt; 0.001), indicating a specific vulnerability in this subgroup that warrants clinical attention. Notably, a statistically significant difference in psychological scores based on biological sex was also confirmed within the healthy control group (p \u0026lt; 0.05 for all scales).\u003c/p\u003e\n\u003cp\u003eThe multivariate models confirmed that both biological sex and daily dosing frequency are robust and independent predictors of distress across all psychological dimensions (Table 3). \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4. Comparison of Psychological Distress Between Patients and Matched Controls\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe final stage of the analysis involved comparing the patient cohort (n=93) with the matched healthy control group (n=186) to assess the global impact of kidney disease on psychological wellbeing.\u003c/p\u003e\n\u003cp\u003eContrary to the initial hypothesis, the healthy control group reported significantly higher levels of depressive symptoms compared to patients (15.71±11.05 vs. 9.69±8.48; F (1,277) = 21.31, p \u0026lt; 0.001). Patients with pediatric-onset kidney disease exhibited lower BDI-II scores compared to the general adolescent and young adult population.\u003c/p\u003e\n\u003cp\u003eThe assessment of anxiety symptoms reinforced this inverse trend. For STAI-Y2, healthy controls scored significantly higher than patients (47.16 ±10.80 vs. 41.74±11.56, F (1,277) = 14.89, p \u0026lt; 0.001). (Fig.2)\u003c/p\u003e\n\u003cp\u003eRegarding STAI-Y1, healthy controls again showed a higher mean score (42.33±10.85) compared to patients (39.8±10.93), although this difference showed only a strong trend toward significance (F (1,277) = 3.36, p = 0.067). (Fig.3)\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe transition from pediatric to adult care represents a critical period for patients with kidney disorders, often characterized by increased risks of treatment non-adherence and loss in follow-up. The present study aimed to evaluate the psychological symptomatology of adolescents during this delicate phase, yielding several significant findings.\u003c/p\u003e \u003cp\u003eIn our cohort, the prevalence of clinical depressive symptomatology among adolescent patients with CKD undergoing transition was 22.5%. This finding is consistent with existing literature concerning both pediatric and adult populations, which reports similar indexes in CKD patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConcurrently, the prevalence of anxiety symptoms in this patient group ranged between 31.2% and 38.8%; these values are also in agreement with the rates documented in previous studies, which typically fall within the 30\u0026ndash;45% range [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eContrary to clinical expectations, CKD severity was not significantly associated with anxiety or depression symptoms in our study. Specifically, no correlations emerged regarding age at diagnosis, disease duration, sCr, or eGFR. Even when patients were stratified into simple, intermediate, and complex categories, a classification used in our transition protocol to reflect the cumulative medical burden, psychological scores remained remarkably stable across groups. This lack of statistical significance could suggest that, in adolescents, the clinical severity of the pathology does not directly translate into a proportional psychological burden. In the transition context, a patient with a complex malformation, or a transplant recipient, does not necessarily experience more distress than one with a milder, stable condition.\u003c/p\u003e \u003cp\u003eThese findings contrast sharply with data from adult populations. In adults, declining eGFR values were clearly correlated with increased depression and suicidal ideation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and dialysis patients reported higher depression symptoms compared with pre-dialysis or transplant recipients [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. While recent meta-analytical data [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] confirm a significant psychological burden across all CKD stages, they highlight that adult patients on kidney replacement therapy, particularly hemodialysis, exhibit the highest vulnerability. However, our results align with the few available pediatric studies, such as those by Kiliś-Pstrusińska et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] which found no significant differences in reported depression and anxiety symptoms among children on hemodialysis, peritoneal dialysis, or conservative treatment. This discrepancy between age groups may be attributed to the unique developmental stage of adolescence. Patients in this cohort may maintain a different perception of their disease and \u0026ldquo;patient status\" compared to adults. They often lack a comprehensive understanding of the long-term implications of their condition, only recognizing them when functional limitations begin to significantly interfere with daily life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Adolescents tend to define \"illness\" less in terms of laboratory parameters and eGFR and more in terms of how it affects their social life and independence [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this regard, our study documented a strong correlation between the degree of anxiety and depression and daily dosing frequency. While biological markers failed to reach statistical significance, the number of daily administrations was identified as a robust independent predictor of psychological distress. This \"pill burden\" specifically appeared to increase trait anxiety, suggesting that the requirement of frequent medication intake acts as a chronic environmental stressor that modulates the patient\u0026rsquo;s long-term emotional baseline. The literature consistently shows that higher treatment complexity, including frequent dosing, correlates with poorer health-related quality of life and a greater psychiatric symptom burden [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In pediatric CKD, frequent dosing can exacerbate anxiety and depressive symptoms by increasing caregiver burden and interfering with normal developmental activities [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Managing multiple medication rounds throughout the day serves as a constant, intrusive reminder of the chronic condition of adolescents. Every dose represents a disruption of peer-group activities and school life, reinforcing a \"patient identity\" at the expense of social normalization. Unlike eGFR or creatinine, biochemical values that the patient may not physically perceive, the dosing schedule is a tangible, daily limitation [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Consequently, our data suggests that simplifying therapeutic regimens and reducing dosing frequency could be a highly effective intervention for improving mental health outcomes during the transition phase.\u003c/p\u003e \u003cp\u003eFinally, our analysis identified female gender as a significant risk factor for increased anxiety and depression. This finding aligns with current literature, which consistently reports higher rates of internalizing symptoms among adolescent girls [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Importantly, in our study, this gender disparity was not limited to the clinical cohort; a similar significant difference was observed within the healthy control group. This suggests that the heightened psychological distress observed in female patients is not a direct consequence of CKD, but rather reflects a broader, age-dependent demographic trend within the adolescent population [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In the clinical setting, however, this pre-existing vulnerability can be exacerbated by the burden of chronic illness. For transition teams, these results emphasize that gender is a more reliable predictor of emotional fragility than kidney function, highlighting the need for gender-tailored psychological screening and support. It is also possibile that females reported higher psychological symptomatology due to gender stereotypes, while males underreported psychological vulnerability to preserve a culturally reinforced image of strength.\u003c/p\u003e \u003cp\u003eA final notable finding of our study concerns the comparison between adolescent patients with CKD and their healthy peers. Unexpectedly, our data reveals that patients reported lower scores on both the depression and anxiety scales compared to the control group. This may be explained by the \u0026ldquo;resilience paradox\u0026rdquo; in chronic illness, which posits that adolescents facing long-term medical challenges may develop more effective coping mechanisms compared to healthy peers [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This psychological advantage may be attributed to several factors. First, the structured multidisciplinary support provided within a transition program could offer a protective emotional buffer that healthy peers lack. Additionally, the close parental supervision and stronger family bonds often necessitated by CKD treatment may mitigate the social stressors and sense of isolation frequently experienced by healthy adolescents during this turbulent developmental phase [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. These findings suggest that, despite the objective burden of the disease, a well-supported transition pathway can effectively safeguard the mental health of adolescent patients [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral limitations must be acknowledged. First, the cross-sectional design of the study precludes establishing definitive causal relationships between the identified predictors and psychological outcomes. Although daily dosing frequency emerged as a strong predictor of anxiety and depression, only longitudinal studies can confirm whether reducing this burden leads to direct improvements in mental health over time. Second, the study was conducted at a single tertiary care center, which may limit the generalizability of the findings to other transition programs with different multidisciplinary structures or patient populations. In addition, the relatively small sample size of the clinical cohort may have reduced the statistical power to detect subtle differences between subgroups. Third, the psychological assessment relied exclusively on two self-reported questionnaires (BDI-II and STAI). Although these are validated and widely used, they remain susceptible to social desirability bias or the \"denial\" effect, whereby patients may underreport symptoms to appear more resilient to their clinical team. Finally, while several clinical variables were accounted for, other potential confounders, such as socioeconomic status, parental psychological distress, or school performance, were not included in the analysis and should be addressed in future multi-center prospective studies.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, our findings suggest that the psychological well-being of adolescents transitioning with CKD may be influenced more by female gender and by the practical demands of daily treatment than by the objective clinical severity of the disease itself. While parameters such as eGFR and disease duration remain essential for medical management, they did not appear to constitute risk factors for anxiety or depression symptoms in our cohort. Instead, daily dosing frequency emerged as a significant factor associated with psychological distress, suggesting that the \"pill burden\" may act as a tangible daily stressor for these patients.\u003c/p\u003e \u003cp\u003eThe observation of a potential \u0026ldquo;paradox\u0026rdquo;, in which patients reported lower distress levels than their healthy peers, may reflect the protective effects of structured multidisciplinary support, close parental supervision and stronger family bonds. However, these results should be interpreted with caution given the limitations of our study.\u003c/p\u003e \u003cp\u003eUltimately, these insights underscore the value of a holistic approach to the transition process. While further research is needed to confirm these trends, our data suggest that simplifying therapeutic regimens, when clinically feasible, could be a modest but meaningful step toward supporting the emotional well-being of adolescents as they progress to adult care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, D.S.; methodology, D.S. and M.T.; formal analysis, M.T. and P.C.; investigation, D.S. and M.T.; data curation, M.T. and D.S.; writing—original draft preparation, P.C..; writing—review and editing, A.P., M.T. and D.S.; project administration, D.S. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki, and approved by the\u0026nbsp;local Ethics Committee on October 15, 2025 (Ref. code: 379/2025/Oss/AOUBo)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all subjects involved in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research data have been submitted as supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their sincere gratitude to Maria Chiara Tullini for their invaluable support and dedication to the clinical activities throughout this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eDallimore, D.J.; Neukirchinger, B.; Noyes, J. Why Is Transition between Child and Adult Services a Dangerous Time for Young People with Chronic Kidney Disease? A Mixed-Method Systematic Review. \u003cem\u003ePLOS ONE\u003c/em\u003e \u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e13\u003c/em\u003e, e0201098, doi:10.1371/journal.pone.0201098.\u003c/li\u003e\n \u003cli\u003eDrohan, C.; van Zwieten, A.; Mallitt, K.-A.; Durkan, A.; Hahn, D.; Guha, C.; Khalid, R.; Lorenzo, J.; Lah, S.; Didsbury, M.; et al. Emotional, Behavioural and Adaptive Function in Children with Chronic Kidney Disease: The Kids with CKD (KCAD) Study. \u003cem\u003ePediatr Nephrol\u003c/em\u003e \u003cstrong\u003e2025\u003c/strong\u003e, doi:10.1007/s00467-025-07091-8.\u003c/li\u003e\n \u003cli\u003eBlum, R.W.; Garell, D.; Hodgman, C.H.; Jorissen, W.; Okinow, N.A.W.; Orr, D.P.; Slap, G.B. Transition from Child Centered Systems for Adolescents with Chronic Conditions. \u003cem\u003eJournal of Adolescent Health\u003c/em\u003e \u003cstrong\u003e1993\u003c/strong\u003e, \u003cem\u003e14\u003c/em\u003e, 570\u0026ndash;576.\u003c/li\u003e\n \u003cli\u003eMai, K.; Dawson, A.E.; Gu, L.; LaMotte, J.E.; Molitor, S.; Zimmerman, C.T. Common Mental Health Conditions and Considerations in Pediatric Chronic Kidney Disease. \u003cem\u003ePediatr Nephrol\u003c/em\u003e \u003cstrong\u003e2024\u003c/strong\u003e, \u003cem\u003e39\u003c/em\u003e, 2887\u0026ndash;2897, doi:10.1007/s00467-024-06314-8.\u003c/li\u003e\n \u003cli\u003ePerez Gomez, M.V.; Costea, G.-C.; Claus, L.; Cornec-Le Gall, E.; van Eerde, A.M.; Lemoine, S.; Groothoff, J.; Levtchenko, E.; Klein, L.; Pape, L.; et al. Transition of Patients with Hereditary Nephropathies from Paediatric to Adult Care. \u003cem\u003eNephrol Dial Transplant\u003c/em\u003e \u003cstrong\u003e2026\u003c/strong\u003e, \u003cem\u003e41\u003c/em\u003e, 367\u0026ndash;379, doi:10.1093/ndt/gfaf186.\u003c/li\u003e\n \u003cli\u003eWhite PH, Cooley WC; Transitions Clinical Report Authoring Group; American Academy of Pediatrics; American Academy of Family Physicians; American College of Physicians. Supporting the Health Care Transition From Adolescence to Adulthood in the Medical Home. Pediatrics. 2018;142(5):E20182587. \u003cem\u003ePediatrics\u003c/em\u003e \u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e143\u003c/em\u003e, e20183610, doi:10.1542/peds.2018-3610.\u003c/li\u003e\n \u003cli\u003eRosner, R.I. Beck Depression Inventory (BDI). In \u003cem\u003eThe Encyclopedia of Clinical Psychology\u003c/em\u003e; John Wiley \u0026amp; Sons, Ltd, 2015; pp. 1\u0026ndash;6 ISBN 978-1-118-62539-2.\u003c/li\u003e\n \u003cli\u003eWang, Y.-P.; Gorenstein, C. Psychometric Properties of the Beck Depression Inventory-II: A Comprehensive Review. \u003cem\u003eBraz J Psychiatry\u003c/em\u003e \u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e35\u003c/em\u003e, 416\u0026ndash;431, doi:10.1590/1516-4446-2012-1048.\u003c/li\u003e\n \u003cli\u003eSkapinakis, P. Spielberger State-Trait Anxiety Inventory. In \u003cem\u003eEncyclopedia of Quality of Life and Well-Being Research\u003c/em\u003e; Michalos, A.C., Ed.; Springer Netherlands: Dordrecht, 2014; pp. 6261\u0026ndash;6264 ISBN 978-94-007-0753-5.\u003c/li\u003e\n \u003cli\u003eOrtu\u0026ntilde;o-Sierra, J.; Garc\u0026iacute;a-Velasco, L.; Inchausti, F.; Debban\u0026eacute;, M.; Fonseca-Pedrero, E. New Approaches on the Study of the Psychometric Properties of the STAI. \u003cem\u003eActas Esp Psiquiatr\u003c/em\u003e \u003cstrong\u003e2016\u003c/strong\u003e, \u003cem\u003e44\u003c/em\u003e, 83\u0026ndash;92.\u003c/li\u003e\n \u003cli\u003eSchwartz, G.J.; Mun[Combining Tilde]oz, A.; Schneider, M.F.; Mak, R.H.; Kaskel, F.; Warady, B.A.; Furth, S.L. New Equations to Estimate GFR in Children with CKD. \u003cem\u003eJournal of the American Society of Nephrology\u003c/em\u003e \u003cstrong\u003e2009\u003c/strong\u003e, \u003cem\u003e20\u003c/em\u003e, 629, doi:10.1681/ASN.2008030287.\u003c/li\u003e\n \u003cli\u003eAdejumo, O.A.; Edeki, I.R.; Sunday Oyedepo, D.; Falade, J.; Yisau, O.E.; Ige, O.O.; Adesida, A.O.; Daniel Palencia, H.; Sabri Moussa, A.; Abdulmalik, J.; et al. Global Prevalence of Depression in Chronic Kidney Disease: A Systematic Review and Meta-Analysis. \u003cem\u003eJ Nephrol\u003c/em\u003e \u003cstrong\u003e2024\u003c/strong\u003e, \u003cem\u003e37\u003c/em\u003e, 2455\u0026ndash;2472, doi:10.1007/s40620-024-01998-5.\u003c/li\u003e\n \u003cli\u003eKogon, A.J.; Stoep, A.V.; Weiss, N.S.; Smith, J.; Flynn, J.T.; McCauley, E. Depression and Its Associated Factors in Pediatric Chronic Kidney Disease. \u003cem\u003ePediatr Nephrol\u003c/em\u003e \u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e28\u003c/em\u003e, 1855\u0026ndash;1861, doi:10.1007/s00467-013-2497-5.\u003c/li\u003e\n \u003cli\u003eKiliś-Pstrusińska, K.; Medyńska, A.; Adamczyk, P.; Leszczyńska, B.; Szczepańska, M.; Tkaczyk, M.; Wasilewska, A.M.; Zachwieja, K.; Zagożdżon, I.; Kujawa, K.; et al. Depressive Disorders in Children with Chronic Kidney Disease Treated Conservatively. \u003cem\u003eAdv Clin Exp Med\u003c/em\u003e \u003cstrong\u003e2024\u003c/strong\u003e, \u003cem\u003e33\u003c/em\u003e, 1189\u0026ndash;1199, doi:10.17219/acem/175236.\u003c/li\u003e\n \u003cli\u003eHuang, C.W.; Wee, P.H.; Low, L.L.; Koong, Y.L.A.; Htay, H.; Fan, Q.; Foo, W.Y.M.; Seng, J.J.B. Prevalence and Risk Factors for Elevated Anxiety Symptoms and Anxiety Disorders in Chronic Kidney Disease: A Systematic Review and Meta-Analysis. \u003cem\u003eGeneral Hospital Psychiatry\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e69\u003c/em\u003e, 27\u0026ndash;40, doi:10.1016/j.genhosppsych.2020.12.003.\u003c/li\u003e\n \u003cli\u003eJhee, J.H.; Lee, E.; Cha, M.-U.; Lee, M.; Kim, H.; Park, S.; Yun, H.-R.; Jung, S.-Y.; Kee, Y.K.; Yoon, C.-Y.; et al. Prevalence of Depression and Suicidal Ideation Increases Proportionally with Renal Function Decline, Beginning from Early Stages of Chronic Kidney Disease. \u003cem\u003eMedicine (Baltimore)\u003c/em\u003e \u003cstrong\u003e2017\u003c/strong\u003e, \u003cem\u003e96\u003c/em\u003e, e8476, doi:10.1097/MD.0000000000008476.\u003c/li\u003e\n \u003cli\u003eDziubek, W.; Pawlaczyk, W.; Rogowski, L.; Stefanska, M.; Golebiowski, T.; Mazanowska, O.; Krajewska, M.; Kusztal, M.; Kowalska, J. Assessment of Depression and Anxiety in Patients with Chronic Kidney Disease and after Kidney Transplantation-A Comparative Analysis. \u003cem\u003eInt J Environ Res Public Health\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e18\u003c/em\u003e, 10517, doi:10.3390/ijerph181910517.\u003c/li\u003e\n \u003cli\u003eCrawford, K.; Wilson, C.; Low, J.K.; Manias, E.; Williams, A. Transitioning Adolescents to Adult Nephrology Care: A Systematic Review of the Experiences of Adolescents, Parents, and Health Professionals. \u003cem\u003ePediatr Nephrol\u003c/em\u003e \u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e35\u003c/em\u003e, 555\u0026ndash;567, doi:10.1007/s00467-019-04223-9.\u003c/li\u003e\n \u003cli\u003ePinquart, M.; Shen, Y. Depressive Symptoms in Children and Adolescents with Chronic Physical Illness: An Updated Meta-Analysis. \u003cem\u003eJ Pediatr Psychol\u003c/em\u003e \u003cstrong\u003e2011\u003c/strong\u003e, \u003cem\u003e36\u003c/em\u003e, 375\u0026ndash;384, doi:10.1093/jpepsy/jsq104.\u003c/li\u003e\n \u003cli\u003eAlshelleh, S.; Alhouri, A.; Taifour, A.; Abu-Hussein, B.; Alwreikat, F.; Abdelghani, M.; Badran, M.; Al-Asa\u0026rsquo;d, Y.; Alhawari, H.; Oweis, A.O. Prevelance of Depression and Anxiety with Their Effect on Quality of Life in Chronic Kidney Disease Patients. \u003cem\u003eSci Rep\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e12\u003c/em\u003e, 17627, doi:10.1038/s41598-022-21873-2.\u003c/li\u003e\n \u003cli\u003eD\u0026iacute;az-Gonz\u0026aacute;lez de Ferris, M.E.; Pierce, C.B.; Gipson, D.S.; Furth, S.L.; Warady, B.A.; Hooper, S.R. Health-Related Quality of Life in Children with Chronic Kidney Disease Is Affected by the Number of Medications. \u003cem\u003ePediatr Nephrol\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e36\u003c/em\u003e, 1307\u0026ndash;1310, doi:10.1007/s00467-021-04919-x.\u003c/li\u003e\n \u003cli\u003eMai, K.; Dawson, A.E.; Gu, L.; LaMotte, J.E.; Molitor, S.; Zimmerman, C.T. Common Mental Health Conditions and Considerations in Pediatric Chronic Kidney Disease. \u003cem\u003ePediatr Nephrol\u003c/em\u003e \u003cstrong\u003e2024\u003c/strong\u003e, \u003cem\u003e39\u003c/em\u003e, 2887\u0026ndash;2897, doi:10.1007/s00467-024-06314-8.\u003c/li\u003e\n \u003cli\u003eZelikovsky, N.; Nelson, E. Illness Perceptions and Beliefs about Medication: Impact on Health-Related Quality of Life in Adolescent Kidney Transplant Recipients. \u003cem\u003ePediatric Transplantation\u003c/em\u003e \u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e25\u003c/em\u003e, e13988, doi:10.1111/petr.13988.\u003c/li\u003e\n \u003cli\u003eAnderson, T.L.; Valiauga, R.; Tallo, C.; Hong, C.B.; Manoranjithan, S.; Domingo, C.; Paudel, M.; Untaroiu, A.; Barr, S.; Goldhaber, K. Contributing Factors to the Rise in Adolescent Anxiety and Associated Mental Health Disorders: A Narrative Review of Current Literature. \u003cem\u003eJournal of Child and Adolescent Psychiatric Nursing\u003c/em\u003e \u003cstrong\u003e2025\u003c/strong\u003e, \u003cem\u003e38\u003c/em\u003e, e70009, doi:10.1111/jcap.70009.\u003c/li\u003e\n \u003cli\u003eMoreira, J.M.; Bouissou Morais Soares, C.M.; Teixeira, A.L.; Sim\u0026otilde;es e Silva, A.C.; Kummer, A.M. Anxiety, Depression, Resilience and Quality of Life in Children and Adolescents with Pre-Dialysis Chronic Kidney Disease. \u003cem\u003ePediatr Nephrol\u003c/em\u003e \u003cstrong\u003e2015\u003c/strong\u003e, \u003cem\u003e30\u003c/em\u003e, 2153\u0026ndash;2162, doi:10.1007/s00467-015-3159-6.\u003c/li\u003e\n \u003cli\u003ePruette, C.S.; Ranch, D.; Shih, W.V.; Ferris, M.D.-G. Health Care Transition in Adolescents and Young Adults With Chronic Kidney Disease: Focus on the Individual and Family Support Systems. \u003cem\u003eAdvances in Chronic Kidney Disease\u003c/em\u003e \u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e29\u003c/em\u003e, 318\u0026ndash;326, doi:10.1053/j.ackd.2022.02.004.\u003c/li\u003e\n \u003cli\u003eSawyer, S.M.; Drew, S.; Yeo, M.S.; Britto, M.T. Adolescents with a Chronic Condition: Challenges Living, Challenges Treating. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e2007\u003c/strong\u003e, \u003cem\u003e369\u003c/em\u003e, 1481\u0026ndash;1489, doi:10.1016/S0140-6736(07)60370-5.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Clinical Complexity Classification of Pediatric-Onset Kidney Diseases\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eClinical Complexity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eLow Complexity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIntermediate Complexity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHigh Complexity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTransition Care Setting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003e\u003cu\u003ePrimary Care Physician (General Practitioner)\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003e\u003cu\u003eAdult Nephrologist\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003e\u003cu\u003eAdult Nephrologist and Multidisciplinary Team\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eClinical Conditions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026bull; Stage I CKD due to CAKUT (e.g., solitary kidney, hypoplastic kidney, low-to-moderate grade VUR, mild urinary tract dilation)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Follow-up for previous AKI (e.g., uncomplicated typical HUS)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Uncomplicated Calcium Oxalate Nephrolithiasis\u003c/p\u003e\n \u003cp\u003e\u0026bull; Nephrotic Syndrome in remission for \u0026gt;2 years\u003c/p\u003e\n \u003cp\u003e\u0026bull; Recurrent simple Urinary Tract Infections (UTIs)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Enuresis and voiding disorders (without increased bladder pressure)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026bull; Stage II and III CKD\u003c/p\u003e\n \u003cp\u003e\u0026bull; CAKUT with proteinuria and/or hypertension\u003c/p\u003e\n \u003cp\u003e\u0026bull; Follow-up for previous AKI with sequelae\u003c/p\u003e\n \u003cp\u003e\u0026bull; Chronic Glomerulonephritis (GN)\u003c/p\u003e\n \u003cp\u003e\u0026bull; GN secondary to vasculitis\u003c/p\u003e\n \u003cp\u003e\u0026bull; Frequent relapsing or steroid-dependent Nephrotic Syndrome\u003c/p\u003e\n \u003cp\u003e\u0026bull; Alport Syndrome\u003c/p\u003e\n \u003cp\u003e\u0026bull; Uncomplicated ADPKD\u003c/p\u003e\n \u003cp\u003e\u0026bull; Recurrent and/or complicated Nephrolithiasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026bull; Stage IV and V CKD, or ESRD (Dialysis)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Kidney Transplantation\u003c/p\u003e\n \u003cp\u003e\u0026bull; Complex Nephro-uropathies requiring urological follow-up (e.g., PUV and others)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Atypical HUS\u003c/p\u003e\n \u003cp\u003e\u0026bull; Tubulopathies\u003c/p\u003e\n \u003cp\u003e\u0026bull; Ciliopathies (non-ADPKD)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Nephrolithiasis due to metabolic diseases\u003c/p\u003e\n \u003cp\u003e\u0026bull; Metabolic diseases with renal expression (e.g., Cystinosis)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Chronic GN with Renal Insufficiency (RI)\u003c/p\u003e\n \u003cp\u003e\u0026bull; Steroid- or multi-drug resistant Nephrotic Syndrome\u003c/p\u003e\n \u003cp\u003e\u0026bull; Nephropathies associated with syndromes or disabilities\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003eTable 2. Demographic, clinical, and psychological characteristics of patients stratified by clinical complexity\u003c/strong\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSimple\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIntermediate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eComplex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003ePatients, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e51 (54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 680px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSex (Male), \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13 (76.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e32 (61.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15 (60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60 (64.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eWeight (Kg), Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e69.2\u0026plusmn;19.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e65.9\u0026plusmn;15.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e51.0\u0026plusmn;14.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e62.3\u0026plusmn;17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eHeight (cm), Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e172.6\u0026plusmn;11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e169.5\u0026plusmn;10.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e161.4\u0026plusmn;9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e167.0\u0026plusmn;10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eBMI (kg/m^2), Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.1\u0026plusmn;5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.6\u0026plusmn;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20.75\u0026plusmn;2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.2\u0026plusmn;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 680px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical Parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eAge at Diagnosis (years), Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.9\u0026plusmn;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.8\u0026plusmn;6.1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.7\u0026plusmn;5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.5\u0026plusmn;5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eTime at Diagnosis (years), Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14.0\u0026plusmn;6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9.8\u0026plusmn;6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12.6\u0026plusmn;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.3\u0026plusmn;6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eSerum Creatinine (mg/dL), Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.8\u0026plusmn;0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.9\u0026plusmn;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.6\u0026plusmn;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.1\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eeGFR (mL/min/1.73m^2)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e111.9\u0026plusmn;15.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e112.63\u0026plusmn;28.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e87.1\u0026plusmn;71.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e102\u0026plusmn;32.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eCKD stage, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e3\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e4\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e5\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (94.1)\u003c/p\u003e\n \u003cp\u003e1 (5.9)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40 (78.4)\u003c/p\u003e\n \u003cp\u003e8 (15.7)\u003c/p\u003e\n \u003cp\u003e3 (5.9)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (32)\u003c/p\u003e\n \u003cp\u003e8 (32)\u003c/p\u003e\n \u003cp\u003e5 (20)\u003c/p\u003e\n \u003cp\u003e4 (16)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e64 (68.8)\u003c/p\u003e\n \u003cp\u003e17 (18.3)\u003c/p\u003e\n \u003cp\u003e8 (8.6)\u003c/p\u003e\n \u003cp\u003e4 (4.3)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eProteinuria, n (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15 (29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8 (32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eDaily dosing frequency,\u0026nbsp;\u003c/em\u003e\u003cem\u003eMean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.4\u0026plusmn;0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.5\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.8\u0026plusmn;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.8\u0026plusmn;2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 680px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePsychological Assessment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eTime at Test (years),\u003c/em\u003e\u003cem\u003e\u0026nbsp;Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.7\u0026plusmn;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.3\u0026plusmn;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.2\u0026plusmn;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.4\u0026plusmn;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eBDI-II,\u003c/em\u003e\u003cem\u003e\u0026nbsp;Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.8\u0026plusmn;6.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9.0\u0026plusmn;7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.4\u0026plusmn;10.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9.7\u0026plusmn;8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eSTAI-Y\u003c/em\u003e,\u003cem\u003e\u0026nbsp;Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e39.3\u0026plusmn;10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e39.9\u0026plusmn;10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40.0\u0026plusmn;13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e39.8\u0026plusmn;10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eSTAI-Y2\u003c/em\u003e,\u003cem\u003e\u0026nbsp;Mean \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.7\u0026plusmn;11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41.2\u0026plusmn;10.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.1\u0026plusmn;13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41.7\u0026plusmn;11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003eTable 3. Univariate and Multivariate Linear Regression Analysis of Predictors for Depressive Symptoms (BDI-II), State Anxiety (STAI-Y1), and Trait Anxiety (STAI-Y2).\u0026nbsp;\u003c/strong\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePredictor Variable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta; (Unweighted)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eStd. Error\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003et\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate p\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate p\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBDI-II\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eDaily dosing frequency\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eSex (Female)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eAge at Diagnosis\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.820\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eDisease Duration\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.916\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eeGFR\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.778\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eBMI\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTAI-Y1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDaily dosing frequency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSex (Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge at Diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.787\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDisease Duration\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.641\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSTAI-Y2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDaily dosing frequency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSex (Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge at Diagnosis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.681\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDisease Duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.735\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-1.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e(BDI-II Adjusted R\u003csup\u003e2\u003c/sup\u003e = 0.10, p = 0.0007; STAI-Y1 Adjusted R\u003csup\u003e2\u003c/sup\u003e = 0.15, p = 0.0009; STAI-Y2 Adjusted R\u003csup\u003e2\u003c/sup\u003e = 0.17, p = 0.0003)\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"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":"transition, adolescents, chronic kidney disease, psychological wellbeing, comparative design, regression models","lastPublishedDoi":"10.21203/rs.3.rs-9284328/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9284328/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe transition from pediatric to adult care represents a critical phase for adolescents with chronic kidney disease (CKD), potentially affecting both clinical management and psychological well-being. This study aimed to evaluate anxiety and depressive symptoms in adolescents with CKD undergoing a structured transition program and to identify clinical and demographic predictors of psychological distress. Psychological outcomes were also compared with those of a healthy age- and sex-matched control group.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA cross-sectional monocentric study was conducted at the Pediatric Nephrology and Dialysis Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna- Policlinico di Sant\u0026rsquo;Orsola, Bologna, Italy. The study included 93 adolescents and young adults with kidney disorders (mean age 17.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 years) enrolled in a structured transition program. Psychological assessment was performed using BDI-II and STAI-S and T. A healthy control group (n\u0026thinsp;=\u0026thinsp;186) was selected using propensity score matching (1:2 ratio) based on age and sex. Statistical analyses included t-tests, ANOVA, and multivariate linear regression models.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMost patients reported minimal depressive symptoms, whereas clinically significant anxiety was observed in approximately one-third of the cohort. Psychological distress was not associated with clinical indicators such as eGFR, disease duration, or clinical complexity. However, higher daily medication dosing frequency and female sex emerged as significant predictors of increased anxiety and depressive symptoms. Unexpectedly, healthy controls reported higher levels of depression and trait anxiety than patients.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eStructured multidisciplinary transition programs may help support the emotional well-being of adolescents with CKD, emphasizing the importance of holistic care and the potential benefit of simplifying therapeutic regimens whenever clinically feasible.\u003c/p\u003e","manuscriptTitle":"Anxiety And Depression Symptomatology In Adolescents With Kidney Disorders During Pediatric-To-Adult Transition: “Perception Of Illness” And The “Patient Paradox”","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 08:04:56","doi":"10.21203/rs.3.rs-9284328/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2026-05-01T17:39:16+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2026-04-08T17:13:18+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-08T17:11:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-07T22:05:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2026-03-31T17:09:03+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":"ef52088e-21e5-4857-9723-622e0c155bb8","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Major Revisions Needed","date":"2026-05-01T17:39:16+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-01T21:40:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 08:04:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9284328","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9284328","identity":"rs-9284328","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}