Abstract
Background and Objectives: Adult separation anxiety (ASA) has received limited attention in nephrology despite the substantial psychological burden associated with chronic kidney disease (CKD). We examined ASA in CKD in relation to depressive symptoms, parental bonding, perceived expressed emotion, CKD stage, and dialysis status. Materials and Methods: In this multicentre cross-sectional study, 340 adults with CKD (169 dialysis, 171 non-dialysis) were recruited from two tertiary care centres. ASA was assessed with the Adult Separation Anxiety Questionnaire (ASA-27), alongside the Parental Bonding Instrument, Level of Expressed Emotion Scale–Short Form, Beck Depression Inventory (BDI), and Short Form-36 Health Survey. Group comparisons, correlations, multivariate analysis of covariance, and hierarchical linear regression were performed. Results: ASA correlated positively with depressive symptoms (rho = 0.450), maternal overprotection (rho = 0.412), expressed emotion (rho = 0.336), paternal overprotection (rho = 0.326), and CKD stage (rho = 0.166) and negatively with paternal care (rho = −0.212). Dialysis patients had higher ASA and depressive symptom scores, but these differences did not persist once CKD stage was entered as a covariate (p = 0.169 and p = 0.053), reflecting the near-complete overlap between dialysis status and stage 5 disease. Younger age, female sex, higher maternal overprotection, and greater depressive symptom severity were independently associated with higher ASA scores (adjusted R2 = 0.285). Conclusions: ASA appears clinically relevant in CKD and is associated with depressive symptoms and relational factors. Psychosocial assessment in CKD should extend beyond depression. The higher ASA levels observed in dialysis patients cannot be attributed to dialysis treatment itself.
1. Introduction
Chronic kidney disease (CKD) is a common chronic condition that affects approximately 13.4% of adults worldwide and contributes substantially to global morbidity, mortality, and healthcare burden [1]. Beyond its medical consequences, CKD is associated with impaired health-related quality of life and considerable symptom burden, particularly among patients receiving maintenance dialysis [2,3]. Fatigue, pain, sleep disturbance, functional decline, and treatment complexity are common and are frequently accompanied by psychological distress [3,4]. Depression and anxiety symptoms have been reported at higher rates in individuals with CKD than in the general population and are associated with poorer quality of life and adverse clinical outcomes [4].
Within nephrology, research on psychological morbidity has focused mainly on depression, generalized anxiety, and reduced quality of life [3,4]. Although these constructs are clinically important, other potentially relevant forms of distress have received less attention. One such construct is adult separation anxiety. Adult separation anxiety may emerge de novo in adulthood or persist from childhood and is characterized by excessive fear of losing major attachment figures and a strong need to remain close to them [5,6]. In psychiatric and community samples, it has been associated with impaired functioning and comorbidity with mood and anxiety disorders [5,6]. However, its clinical relevance and correlates in CKD remain unclear. This question may be particularly relevant in chronic medical conditions marked by physical vulnerability, uncertainty about disease progression, treatment dependence, and progressive functional limitations [7].
Three constructs that are easily conflated should be distinguished at the outset. Illness-related dependency refers to the practical reliance on treatment, clinical staff, and caregivers that advanced CKD imposes. Attachment processes refer to internalised representations of the availability and responsiveness of significant others, formed in early relationships and relatively stable thereafter [7]. Adult separation anxiety is a symptom dimension defined by excessive fear of losing major attachment figures and distress on separation from them [5,6]. These are not equivalent: a patient may be wholly dependent on dialysis without separation-related distress and may experience marked separation anxiety with little practical dependency. CKD is nonetheless a context in which ASA merits examination, not because dependency constitutes separation anxiety but because the disease course repeatedly confronts patients with the anticipated or actual loss of sources of security, which is the mechanism separation anxiety concerns. Haemodialysis requires attendance at a treatment centre three times per week for approximately four hours per session, and any disruption to this routine—changes in dialysis shift, relocation to a different centre, or loss of a familiar nurse—may function as a separation-related stressor [8]. CKD also progresses irreversibly through stages of declining renal function, and patients experience cumulative losses at each transition: loss of physical independence, dietary freedom, employment capacity, and social participation [2,4]. Furthermore, patients with advanced CKD often rely on a spouse or family member for transportation to dialysis, medication management, and daily activities so that any threat to caregiver availability may activate separation-related fears [9]. Recent evidence indicates that attachment style is associated with mental health and quality of life in haemodialysis patients, supporting the relevance of attachment-based frameworks in this population [10].
Early relational experiences and current interpersonal context may both be relevant to understanding separation-related distress in CKD. Previous studies have linked adult anxiety and mood symptoms to perceived parental care and overprotection during childhood and adolescence [11]. Current caregiving environments may also shape emotional regulation, interpersonal sensitivity, and responses to illness-related stressors. In CKD, increasing care needs, changing family roles, and dependence on ongoing treatment may make both earlier relational patterns and current caregiving dynamics clinically relevant [7,11].
The present study aimed to examine adult separation anxiety in individuals with CKD in relation to developmental, relational, and clinical variables. On the basis of previous work, we hypothesised that greater ASA symptom severity would be associated with higher depressive symptom levels, poorer health-related quality of life, more negative perceived expressed emotion, lower perceived parental care and higher perceived parental overprotection, as well as with more advanced CKD stage and dialysis treatment. The directions specified for the parental bonding dimensions follow the literature linking low care and high overprotection to adult anxiety and mood symptoms [11,12,13,14]. The ASA-27 total score was designated the primary outcome and the hierarchical regression model for ASA the primary analysis; all remaining analyses were secondary and exploratory. We also sought to identify factors significantly associated with adult separation anxiety using hierarchical regression analysis.
2. Materials and Methods
2.1. Study Design and Setting
This multicentre cross-sectional observational study was conducted in the nephrology outpatient clinics and dialysis units of two tertiary care centres: Turgut Özal University Malatya Training and Research Hospital and İnönü University Turgut Özal Medical Center. The study was designed, conducted, and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement for cross-sectional studies (Supplementary File S1). The study examined the associations of adult separation anxiety with developmental, relational, and clinical variables in adults with chronic kidney disease (CKD). Adults with CKD across different disease stages, including both dialysis and non-dialysis patients, were eligible.
2.2. Participants
Adult patients with CKD evaluated at the two centres between 10 February 2026 and 10 May 2026 were consecutively enrolled if eligible. CKD was diagnosed by a nephrologist according to the KDIGO criteria [15]. Inclusion criteria were age ≥18 years, confirmed CKD, literacy, sufficient cognitive capacity to complete the study measures, and written informed consent. Exclusion criteria were moderate-to-severe dementia, severe psychiatric disorders such as schizophrenia or bipolar disorder, and neurological or cognitive impairment interfering with questionnaire completion. All eligible patients presenting during the recruitment period were approached, and the achieved sample size was determined by this consecutive enrolment rather than by a prior target. A sensitivity power analysis was therefore performed to establish what the achieved sample could detect. With a two-sided α of 0.05 and 80% power, the study was able to detect a between-group difference in Cohen’s d ≥ 0.31 (n = 171 versus 169), a bivariate correlation of |r| ≥ 0.15 (N = 340), and an effect of f2 ≥ 0.05 for the final regression model with ten predictors (N = 328), corresponding to R2 ≥ 0.05. The study was thus powered to detect small to medium effects. A total of 340 patients meeting the eligibility criteria were enrolled. Data were collected simultaneously at both centres by multiple trained investigators working across nephrology outpatient clinics and dialysis units over a period of approximately three months. Dialysis patients were approached during their routine thrice-weekly haemodialysis sessions, while non-dialysis patients were recruited consecutively during scheduled follow-up visits. Questionnaire completion took approximately 20–25 min per participant.
2.3. Measures
2.3.1. Sociodemographic and Clinical Data Form
Sociodemographic and clinical data were collected using a form developed by the investigators. Variables included age, sex, marital status, educational level, living arrangement, number of siblings, employment status, comorbid medical conditions, current or past psychiatric treatment, disease duration and stage, dialysis status and duration, current treatments/medications, hospitalization history, and caregiver-related information. Data were obtained from patient interviews and medical records.
2.3.2. Adult Separation Anxiety Questionnaire (ASA-27)
Adult separation anxiety symptoms were assessed using the 27-item Adult Separation Anxiety Questionnaire (ASA-27) developed by Manicavasagar et al. [16]. Items are rated on a four-point Likert scale, with higher total scores indicating greater symptom severity. The Turkish version has been validated [17].
2.3.3. Parental Bonding Instrument (PBI)
Perceived parental care and overprotection/control during the developmental period were assessed using the Parental Bonding Instrument (PBI) [18]. The instrument yields separate maternal and paternal scores for care and overprotection/control during the first 16 years of life. Each item is rated 0–3. The care subscale comprises 12 items (1, 2, 4, 5, 6, 11, 12, 14, 16, 17, 18, and 24), of which six (2, 4, 14, 16, 18, and 24) are reverse-scored, giving a possible range of 0–36. The overprotection subscale comprises 13 items (3, 7, 8, 9, 10, 13, 15, 19, 20, 21, 22, 23, and 25), of which six (3, 7, 15, 21, 22, and 25) are reverse-scored, giving a possible range of 0–39. Higher scores reflect greater perceived care or overprotection. No clinical cut-offs were applied; subscale scores were analysed as continuous variables. The Turkish version has been validated [19]. In the present sample, Cronbach’s α was 0.94 for maternal care, 0.74 for maternal overprotection, 0.93 for paternal care, and 0.85 for paternal overprotection.
2.3.4. Level of Expressed Emotion Scale–Short Form (LEE-SF)
Perceived expressed emotion was assessed using the Level of Expressed Emotion Scale–Short Form (LEE-SF) [20,21,22]. Participants were instructed to rate a significant other with whom they lived, with reference to the preceding year. The scale evaluates perceived expressed emotion across intrusiveness, lack of emotional support, irritability, and criticism. Each of the 30 items is rated 1–4, and the 12 negatively worded items are reverse-scored before summing, giving a possible total range of 30–120. Higher total scores indicate more negative perceived expressed emotion. In the present sample, Cronbach’s α for the total score was 0.93.
2.3.5. Beck Depression Inventory (BDI)
Depressive symptoms were assessed using the 21-item Beck Depression Inventory (BDI), developed by Beck et al. [23]. Items are scored from 0 to 3, with higher total scores indicating greater depressive symptom severity. The Turkish version has demonstrated validity and reliability [24].
2.3.6. Short Form-36 Health Survey (SF-36)
Quality of life was assessed using the SF-36 [25], a 36-item measure evaluating eight health domains with scores ranging from 0 to 100. Domain scores were computed according to the standard scoring algorithm. Higher scores indicate better health-related quality of life. The Turkish version has been shown to be valid and reliable [26]. In the present sample, Cronbach’s α ranged from 0.74 (social functioning) to 0.96 (role physical) across the eight domains.
2.4. Data Collection Procedure
Data were collected using the sociodemographic and clinical data form, together with the self-report questionnaires. Adult separation anxiety symptoms, perceived parental care and overprotection, perceived expressed emotion from a significant other, depressive symptoms, and quality of life were assessed by self-report. CKD-related clinical data were obtained from patient interviews and medical records, and CKD staging was determined by a nephrologist according to the KDIGO criteria [15].
2.5. Statistical Analysis
Data were analyzed using IBM SPSS Statistics 26.0. Distribution of continuous variables was assessed using histograms, Q–Q plots, and the Kolmogorov–Smirnov test. Non-normally distributed continuous variables are presented as median and interquartile range (Q1–Q3), normally distributed continuous variables as mean ± standard deviation, and categorical variables as number and percentage [n (%)]. Missing data were minimal, affecting no variable by more than 1.2%. Analyses were conducted on complete cases, giving analytic samples of N = 336 for the MANCOVA and N = 328 for the regression models. Mann–Whitney U tests were used to compare psychosocial variables, depressive symptoms, adult separation anxiety, and quality of life scores according to dialysis status. Effect sizes for group comparisons were calculated using the r coefficient derived by dividing the Z statistic by the square root of the total sample size. Spearman’s rank correlation analysis was used to examine associations among clinical and psychosocial variables. Because the group comparisons and correlations were secondary and exploratory, the Holm procedure was applied within each family of tests (19 group comparisons and 36 correlations), and both unadjusted and adjusted p values are reported. Multivariate analysis of covariance (MANCOVA) was performed to evaluate differences according to dialysis status. Dialysis status, sex, and comorbidity were entered as fixed factors, and age, CKD duration, and CKD stage were entered as covariates; because dialysis status and CKD stage are closely related, the model was estimated both without and with CKD stage, and collinearity between them was quantified using variance inflation factors and Cramér’s V. Multivariate effects were assessed using Pillai’s Trace, which is the most robust multivariate criterion to violations of distributional assumptions, and univariate effect sizes were reported as partial eta squared (ηp2). Homogeneity of covariance matrices was examined with Box’s M test, equality of error variances with Levene’s test, multivariate outliers with Mahalanobis distance, and homogeneity of regression slopes with dialysis status × covariate interaction terms. Hierarchical multiple linear regression analyses were conducted to examine factors associated with total ASA and total BDI scores. Variables were entered in three sequential blocks based on theoretical considerations. Block 1 included demographic and clinical variables (age, sex, comorbidity status, and CKD stage) to account for background characteristics. Block 2 added relational variables (PBI maternal care, PBI maternal overprotection, PBI paternal care, PBI paternal overprotection, and LEE-SF total score) to assess the incremental contribution of developmental and current interpersonal factors. Block 3 added the reciprocal psychological variable (BDI total score for the ASA model; ASA-27 total score for the BDI model). The two reciprocal models were estimated in order to establish whether each outcome retained an association with the relational variables once the other was accounted for; given the cross-sectional design, they are not intended to support inferences about direction. Sex was coded with male as the reference category and comorbidity with absence as the reference category. All continuous predictors were entered as linear terms. The assumptions of linearity and homoscedasticity were examined using partial regression plots, residual-versus-predicted scatter plots, and the Breusch–Pagan test; no substantial departures from linearity were observed, and because residual variance increased with predicted values in the BDI model (Breusch–Pagan p = 0.001), its coefficients were additionally estimated with heteroscedasticity-consistent (HC3) standard errors as a sensitivity analysis. Model fit was assessed using R2 and adjusted R2, and the change in R2 with the associated F-change statistic is reported for each block. Regression coefficients were reported as unstandardized coefficients (B) with 95% confidence intervals and standardized coefficients (β). Multicollinearity was assessed using variance inflation factor (VIF) and tolerance values. All tests were two-tailed, and p < 0.05 was considered statistically significant. An AI-based tool (Claude Opus 5.5, Anthropic, San Francisco, CA, USA) was used to support language editing and the preparation of the scoring and statistical analysis syntax (see Acknowledgments). The authors take full responsibility for all scientific content, data analyses, interpretations, and conclusions.
2.6. Ethics
Ethical approval for this study was obtained under approval no. 2026/6, dated 9 February 2026. The study was conducted in accordance with the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants prior to enrolment.
3. Results
The mean age of the patients with chronic kidney disease was 61.56 ± 14.07 years (range 19–91 years), and 153 participants (45.0%) were female. The mean duration of chronic kidney disease was 7.85 ± 5.89 years (range 1–34 years), 179 patients (52.6%) were in CKD stage 5, and 169 participants (49.7%) were receiving dialysis treatment; among those on dialysis, 162 patients (95.9% of the dialysis group) were undergoing dialysis three times per week. All dialysis patients were receiving maintenance haemodialysis; no patient was on peritoneal or home dialysis. Other sociodemographic and clinical characteristics are presented in Table 1.
Table 1.
Sociodemographic and clinical characteristics of the study population.
Dialysis patients had higher BDI and ASA scores, higher maternal care, higher LEE irritability scores, and lower scores across all SF-36 domains, together with lower paternal overprotection (Table 2). After Holm correction, 11 of the 19 comparisons remained significant. The largest effects were observed for SF-36 general health (r = 0.390), vitality (r = 0.356), PBI maternal care (r = 0.350), and LEE irritability (r = 0.343); the remaining effects were small. The comparisons for SF-36 physical functioning, PBI paternal care, PBI maternal overprotection, LEE total, LEE intrusiveness, LEE emotional support deficit, LEE criticism, and BDI total were not significant after correction for multiple comparisons; of these, the differences in SF-36 physical functioning, PBI paternal care, and BDI total were significant only before correction and should be regarded as exploratory.
Table 2.
Comparison of psychosocial and quality-of-life scale scores between dialysis and non-dialysis patients.
Total ASA score was positively correlated with total BDI score (rho = 0.450, p < 0.001), maternal overprotection (rho = 0.412, p < 0.001), paternal overprotection (rho = 0.326, p < 0.001), total LEE score (rho = 0.336, p < 0.001), and CKD stage (rho = 0.166, p = 0.002) and negatively correlated with paternal care (rho = −0.212, p < 0.001). Total BDI score was positively correlated with total LEE score (rho = 0.348, p < 0.001), maternal overprotection (rho = 0.270, p < 0.001), and paternal overprotection (rho = 0.263, p < 0.001), and negatively correlated with paternal care (rho = −0.341, p < 0.001). Total LEE score was negatively correlated with the PBI care subscales (rho = −0.470 to −0.306; all p < 0.001). Of the 36 correlations, 22 remained significant after Holm correction; the association between CKD stage and total BDI score (rho = 0.128, p = 0.018) was among those that did not (Table 3).
Table 3.
Correlations between clinical variables, parental bonding, expressed emotion, depression, and adult separation anxiety scores in patients with chronic kidney disease.
MANCOVA including age and CKD duration as covariates showed a significant multivariate effect of dialysis status on adult separation anxiety, depressive symptoms, and quality-of-life subscales (Pillai’s Trace = 0.275; F (10, 321) = 12.166; p < 0.001). In this model, covariate-adjusted means were higher in dialysis patients for total ASA (F = 7.615; p = 0.006; ηp2 = 0.023) and total BDI (F = 11.101; p < 0.001; ηp2 = 0.033), and lower for all eight SF-36 domains (all p < 0.001). However, dialysis status and CKD stage were almost completely overlapping in this cohort: 166 of 168 dialysis patients (98.8%) were in CKD stage 5, compared with 12 of 168 non-dialysis patients (7.1%) (Cramér’s V = 0.918; Spearman rho = 0.874; p < 0.001), with variance inflation factors of 3.43 for dialysis status and 3.39 for CKD stage. When CKD stage was added as a covariate, the multivariate effect was attenuated (Pillai’s Trace = 0.112; F (10, 320) = 4.049; p < 0.001) and the differences in total ASA (F = 1.900; p = 0.169; ηp2 = 0.006), total BDI (F = 3.775; p = 0.053; ηp2 = 0.011) and SF-36 social functioning (F = 2.798; p = 0.095) were no longer significant, while the remaining SF-36 domains continued to favour the non-dialysis group (Table 4). Box’s M indicated heterogeneity of covariance matrices between the dialysis groups (M = 220.86; χ2(55) = 213.97; p < 0.001) and Levene’s test comparing the dialysis groups was significant for 7 of the 10 dependent variables; nine of 336 cases (2.7%) exceeded the Mahalanobis criterion at p < 0.001. Homogeneity of regression slopes was supported for the dialysis status × CKD stage (all p > 0.07) and dialysis status × CKD duration (all p > 0.17) interactions across all dependent variables; the dialysis status × age interaction was significant for total BDI (p = 0.031) and SF-36 social functioning (p = 0.021), so the adjusted comparisons for these two outcomes should be interpreted with caution.
Table 4.
Impact of dialysis status on adult separation anxiety, depressive symptoms, and health-related quality of life: Results of Multivariate Analysis of Covariance (MANCOVA).
In hierarchical multiple linear regression (N = 328), Models 1, 2, and 3 explained 8.5%, 24.2%, and 30.7% of the variance in total ASA score, respectively; each block produced a significant increment (ΔR2 = 0.085, F (4, 323) = 7.479; ΔR2 = 0.157, F(5, 318) = 13.209; ΔR2 = 0.065, F(1, 317) = 29.634; all p < 0.001). In the final model (R2 = 0.307, adjusted R2 = 0.285, p < 0.001), age (B = −0.136, 95% CI −0.251 to −0.022, β = −0.117, p = 0.020), female sex (B = 5.562, 95% CI 2.264 to 8.860, β = 0.169, p = 0.001), PBI maternal overprotection (B = 0.708, 95% CI 0.296 to 1.120, β = 0.249, p < 0.001), and total BDI score (B = 0.541, 95% CI 0.345 to 0.736, β = 0.296, p < 0.001) were independently associated with total ASA score (Table 5). CKD stage was not independently associated with ASA in the final model (p = 0.604). All variance inflation factors were below 2.8.
Table 5.
Hierarchical multiple linear regression analysis of variables related to ASA scores in patients with chronic kidney disease.
In the hierarchical regression model for total BDI score (N = 328), Models 1, 2, and 3 explained 10.9%, 26.0%, and 32.4% of the variance, respectively (all ΔR2 p < 0.001). In the final model (R2 = 0.324, adjusted R2 = 0.302, p < 0.001), age (B = 0.157, β = 0.246, p < 0.001), female sex (B = 1.831, β = 0.102, p = 0.047), CKD stage (B = 1.340, β = 0.171, p = 0.002), PBI maternal overprotection (B = −0.250, β = −0.160, p = 0.030), PBI paternal care (B = −0.294, β = −0.239, p < 0.001), total LEE score (B = 0.116, β = 0.180, p = 0.002), and total ASA score (B = 0.158, β = 0.289, p < 0.001) were independently associated with depressive symptom severity (Table 6). With heteroscedasticity-consistent (HC3) standard errors, these associations remained significant, except that of maternal overprotection (p = 0.092).
Table 6.
Hierarchical multiple linear regression analysis of variables related to BDI scores in patients with chronic kidney disease.
To aid interpretation, the unstandardised regression coefficients (B) indicate the expected difference in the outcome per unit difference in each predictor. In the final ASA model, female patients scored on average 5.6 points higher on the ASA-27 than male patients, each one-point difference in BDI corresponded to a 0.54-point difference in ASA-27 score, and each one-point difference in maternal overprotection corresponded to a 0.71-point difference in ASA-27 score. In the final BDI model, each one-point difference in ASA-27 corresponded to a 0.16-point difference in BDI, and each additional CKD stage corresponded to a 1.34-point difference in BDI score.
4. Discussion
This study suggests that adult separation anxiety (ASA) is a clinically relevant and under-recognized dimension of psychological distress in chronic kidney disease (CKD). To our knowledge, adult separation anxiety has not previously been examined in adults with CKD, and the present findings should be regarded as exploratory. ASA scores were higher in patients receiving dialysis, although this difference could not be separated from disease stage, and multivariable analyses showed that younger age, female sex, higher perceived maternal overprotection, and greater depressive symptom severity were independently associated with ASA after adjustment for demographic and clinical factors. These findings suggest that ASA in CKD reflects not only general psychological distress but also a distinct dimension shaped by disease burden and interpersonal factors.
ASA and depressive symptom scores were higher in patients receiving dialysis, but this observation requires careful qualification. Dialysis status and advanced CKD were almost completely overlapping in this cohort: 98.8% of dialysis patients were in stage 5, and the two variables correlated at rho = 0.874. When CKD stage was entered as a covariate, the differences in ASA and depressive symptoms were no longer significant. The group difference therefore cannot be attributed to dialysis treatment as distinct from advanced disease and should be read as a difference between groups that differ simultaneously in modality and in stage. Physical symptoms, functional limitations, reduced quality of life, and psychiatric symptoms are all more common at advanced CKD stages [2,3,4], and dialysis is a clinical expression of that burden, requiring regular dependence on treatment for survival and accompanied by reduced autonomy, greater care needs, and more tangible illness-related uncertainty [3,9]. Whether treatment dependency contributes to separation-related distress over and above disease severity is a hypothesis that this design cannot test; it would require cohorts in which stage and modality are not confounded, for example, patients at the same stage receiving different modalities.
The association between ASA and depressive symptoms suggests that separation-related distress in CKD should be understood within a broader pattern of emotional burden. Studies in other clinical populations have shown that ASA is associated with depressive symptoms and may co-occur with greater symptom severity, psychiatric comorbidity, and functional impairment [27,28,29,30]. In our study, depressive symptom severity remained independently associated with ASA after adjustment for demographic and clinical variables. Although depressive symptoms in CKD are often linked to health loss and functional decline, ASA may be more closely related to threats to security and caregiving. These domains may overlap, but ASA should not be reduced to depression alone. The correlation between ASA and depressive symptoms (rho = 0.450) represents a medium-to-large effect, and ASA was also moderately associated with perceived expressed emotion (rho = 0.336) and with perceived parental overprotection (rho = 0.412 maternal, 0.326 paternal), whereas the association with CKD stage was small (rho = 0.166). Because ASA and depressive symptoms were each entered as a predictor of the other, these analyses establish independent associations but cannot indicate direction.
Younger age, female sex, higher perceived maternal overprotection, and higher depressive symptom severity were independently associated with ASA. The associations with younger age and female sex are consistent with previous reports suggesting that separation-related symptoms may be more pronounced in specific demographic subgroups [27,31,32]. Higher perceived maternal overprotection/control was also independently associated with ASA, and this is consistent with the broader literature linking parental overprotection and control to adult anxiety symptoms [11,12,13,14]. The finding suggests that ASA in CKD may be linked not only to current emotional distress but also to internalized representations of earlier relational experiences [12,13,14]. Because the PBI is retrospective, current mood state may also colour the recollection of parenting, and the cross-sectional design does not allow early relationship patterns to be treated as causes of current symptoms. Perceived expressed emotion was associated with ASA in bivariate analysis but was not independently associated with it in the final model, suggesting a closer link with earlier relationship patterns than with the immediate relational climate [9].
In the secondary analyses, depressive symptoms were independently associated with more advanced CKD stage, lower perceived paternal care, more negative perceived expressed emotion, and higher ASA. This suggests that depressive symptoms in this sample relate to both illness burden and interpersonal context. In the CKD literature, depressive symptoms have long been associated with disease severity, functional impairment, reduced quality of life, psychosocial burden, and poorer clinical outcomes; accordingly, the finding that CKD stage remained independently associated with depressive symptoms is consistent with previous work. By contrast, CKD stage was not independently associated with ASA in the final model, which suggests that separation-related distress should not be interpreted merely as a psychological extension of somatic disease severity. Rather, ASA appears to be more closely linked to enduring interpersonal sensitivities related to earlier relationship patterns, whereas depressive symptoms appear to be more strongly associated with both clinical disease burden and current relational context. The association between lower perceived paternal care and depressive symptoms may indicate that early experiences related to emotional support and self-worth development remain relevant to depressive vulnerability in the context of chronic illness [4,8,33]. Maternal overprotection was positively correlated with depressive symptoms (rho = 0.270) but had a negative coefficient in the multivariable model, which reached significance only after ASA was entered and was not robust to heteroscedasticity-consistent standard errors; this sign reversal probably reflects statistical suppression arising from its overlap with ASA and paternal overprotection and should not be interpreted as a protective association.
Patients receiving dialysis had lower scores across all eight SF-36 domains, and the differences in physical functioning, role physical, bodily pain, general health, vitality, role emotional, and mental health persisted after CKD stage was added as a covariate. This is consistent with previous literature showing that quality of life in CKD and renal replacement therapy is substantially impaired, particularly in physical domains [34,35,36]. The difference in social functioning did not persist after adjustment for CKD stage, and the comparison for physical functioning did not survive correction for multiple comparisons, so these two findings should be regarded as exploratory. As with the psychiatric outcomes, the near-complete overlap between dialysis status and stage 5 disease means that these differences reflect groups that differ in both modality and disease severity, and the contribution of dialysis itself cannot be isolated.
Taken together, these findings suggest that psychosocial assessment in CKD need not be confined to depressive symptoms and that separation-related distress is a dimension that can be identified with a brief self-report instrument. Patients with elevated ASA scores may benefit from targeted psychological interventions such as attachment-informed psychotherapy or structured cognitive-behavioural approaches focused on separation fears, which have demonstrated efficacy in psychiatric populations but have not been tested in nephrology settings [5,6]. Beyond this, the clinical significance of ASA in CKD remains to be established, and the following possibilities are offered as hypotheses for future research rather than as implications of the present findings. None of the outcomes concerned was measured in this study. It is unknown whether elevated ASA is associated with treatment adherence, with reluctance to initiate dialysis, with transplant referral or waitlisting, or with transitions between treatment modalities [37,38]; whether recognising ASA helps clinicians interpret behaviours such as marked distress when dialysis shifts are changed or reluctance to consider home-based therapies [8]; or whether brief screening for early relational experiences at the time of CKD diagnosis would identify patients who benefit from psychosocial referral [10,11]. Prospective studies measuring these endpoints directly would be required to answer any of these questions, and the clinical validity and any actionable threshold for ASA screening in CKD have not been established. Establishing them would align with the growing recognition that comprehensive psychosocial evaluation can improve coping, quality of life, and clinical outcomes in patients with chronic kidney disease [4,39,40].
The main strengths of this study include its multicentre design, the inclusion of both dialysis and non-dialysis patients within a relatively large clinical sample, and the simultaneous evaluation of ASA with clinical and interpersonal variables. However, the findings should be interpreted in light of several limitations. The cross-sectional design precludes causal inference, and the direction of observed associations cannot be established. Dialysis status and CKD stage were almost completely confounded, so the study cannot determine whether dialysis treatment contributes to psychological distress independently of advanced disease. Self-report measures increase the risk of common method bias, and retrospective assessment of parental relationship patterns may have introduced recall bias, particularly among participants with higher depressive symptom levels [18,41]. A response pattern specific to the maternal PBI form warrants caution in interpreting the maternal findings: on that form, higher perceived care, higher perceived control and higher perceived autonomy-granting tended to co-occur, whereas on the paternal form the autonomy-granting items related to the control items in the expected inverse direction. Internal consistency for the maternal overprotection subscale was correspondingly lower than for the paternal subscale (α = 0.74 versus 0.85). However, the direction of the association between perceived overprotection and ASA was the same for both parents, so this finding does not rest on the maternal form alone. The study used a screening instrument (ASA-27) rather than a diagnostic interview; the findings therefore reflect adult separation anxiety symptom severity rather than adult separation anxiety disorder as defined by DSM-5, and no diagnostic cut-off was applied. Internal consistency could not be calculated for the ASA-27 and the BDI because only total scores were recorded for these instruments. In the Turkish SF-36 form used, the bodily pain item offered five response options without an intermediate category, which may limit its sensitivity to moderate pain. The sample was drawn from two centres in Turkey, which may limit the generalisability of the findings to other cultural contexts. Female sex was independently associated with ASA; however, we did not perform fully sex-stratified subgroup analyses, and future studies should examine sex differences in ASA in CKD populations more explicitly. Finally, the absence of a healthy or non-CKD chronic disease comparator means that whether ASA levels in this sample are elevated relative to other populations cannot be determined.
5. Conclusions
ASA in CKD appears to represent a clinically relevant psychological dimension associated with depressive symptoms, perceived parental overprotection, and perceived expressed emotion. Psychosocial assessment in CKD should extend beyond depression to include separation-related distress. Because dialysis status and advanced CKD stage were almost completely overlapping in this cohort, the higher ASA levels observed in dialysis patients cannot be attributed to dialysis treatment itself. Future longitudinal studies are needed to clarify the role of ASA in clinical course and psychosocial adaptation, to test whether it relates to clinical endpoints such as treatment adherence, and to evaluate whether targeted interventions addressing separation anxiety can improve outcomes in this population.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/medicina62112090/s1, Supplementary File S1: STROBE Statement—Checklist of Items That Should Be Included in Reports of Cross-Sectional Studies.
Author Contributions
Conceptualization, M.F.U. and H.Y.; methodology, H.Y.; formal analysis, H.Y.; investigation, M.F.U., İ.D., N.G.Y. and H.B.B.; data curation, M.F.U. and N.G.Y.; writing—original draft preparation, H.Y. and Z.D.Y.; writing—review and editing, M.F.U., O.S.Y., Z.D.Y., İ.D., H.B.B. and M.K.; supervision, M.F.U. and H.B.B. 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 Health Sciences Scientific Research Ethics Committee of Malatya Turgut Özal University (protocol code 2026/6; date of approval: 9 February 2026).
Informed Consent Statement
Written informed consent was obtained from all subjects involved in the study prior to enrolment.
Data Availability Statement
The data presented in this study are available on request from the corresponding author. The data are not publicly available because they contain clinical patient information and are subject to ethical and institutional restrictions; any release is subject to approval by the relevant ethics committee and institution.
Acknowledgments
The authors thank the patients who participated in this study and the staff of the nephrology outpatient clinics and dialysis unit for their support during data collection. During the preparation of this manuscript, the authors used Claude (Anthropic) for the purposes of language editing, manuscript preparation, and preparation of the scoring and statistical analysis syntax. The authors have reviewed and edited the output and take full responsibility for the content of this publication.
Conflicts of Interest
The authors declare no conflicts of interest.
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