Symptom–Psychosocial Mismatch in Chronic Kidney Disease: Development and Clinical Implications of a Novel Mismatch Index

Introduction

Chronic kidney disease (CKD), especially end-stage kidney disease (ESKD) impose a complex burden that extends beyond physiological decline. The presentation of clusters of symptoms such as pain, fatigue, sleep disturbance, nausea, dyspnoea, and pruritus, together with symptoms of anxiety, depressive disorder, illness-related anxieties, loss of autonomy, and existential distress, can be prevalent in patients.^1-4 With the progression of CKD, these interrelated burdens result in increasing quality of life (QoL) decline, treatment dissatisfaction, and health care utilization,^5-7 and while many studies have examined symptom burden and psychosocial distress separately, their relationship has received limited attention. A core assumption woven throughout much of nephrology and palliative-care literature is that symptom severity translates into severity of psychosocial distress.⁸ This proportionality is the basis of clinical pathways, screening algorithms, and research models. However, clinical observations frequently contradict this assumption. Patients with relatively mild physical symptoms may report substantial emotional distress, whereas others with severe physical symptoms may demonstrate muted psychological expression. Although often observed in clinical practice, this discordance has rarely been systematically defined or quantified in kidney disease populations.

We present the notion of symptom-psychosocial mismatch (SPM), a new, clinically relevant difference between a patient’s physical symptom burden and their psychosocial distress severity. The misfit can take two different forms: psychosocial-dominant mismatch (positive mismatch) characterized by high distress despite mild symptoms, or symptom-dominant mismatch (negative mismatch) in which patients experience severe symptoms but exhibit relatively low distress.

Both patterns represent distinct trajectories. This psychosocial-dominant mismatch represents hidden distress, where clinically relevant psychological suffering lies unseen by the standard symptom-centric assessment, whereas symptom-dominant mismatch accounts for resigned coping or emotional suppression, which is suggestive of burnout, resignation, or adaptive dissociation.

To operationalize this construct, we devised the mismatch index (MI), a simple quantitative summary measure that describes the difference between psychosocial distress and symptom burden: MI = Psychosocial distress score - Symptom burden score.

A positive MI indicates patients whose emotional pain exceeds their physical manifestations, and a negative MI indicates patients whose physical pain is underappreciated by psychological screening alone. This index provides a complementary dimension to burden of illness understanding by describing what traditional measurement fails to do, the importance of analyzing misfit.

To our knowledge, the symptom–psychosocial discordance using a composite index has not been studied before. This study aimed to define and quantify SPM in CKD and ESKD with the MI and to explore its clinical relevance as an indicator of hidden distress. Although discordance between physical symptoms and emotional distress has been described in psychosomatic research, oncology, and heart failure populations, it has not been systematically operationalized in nephrology using routinely applied symptom and distress instruments, and this study therefore explores one possible way to operationalize this concept in CKD. The aim was not to claim discovery of this phenomenon, but to develop a pragmatic framework to quantify SPM in CKD and ESKD populations using measures already commonly employed in clinical care.

Methods

An observational cross-sectional single-center study was conducted over ten months in Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. Adults (≥18 years) with CKD stages 3–5 Including those on dialysis were recruited. Patients were required to be clinically stable for no <2 weeks and to be able to provide informed consent. Exclusion criteria included acute kidney injury, severe psychiatric illness, dementia or cognitive impairment, recent ICU admission (<14 days), or inability to complete study questionnaires.

Sample size was estimated to reflect an anticipated 50% prevalence of SPM (maximal variance), with a 95% confidence level, and 15% margin of error, resulting in a total sample size of 134 recruited subjects. Although the sample size calculation was based on estimating the prevalence of symptom–psychosocial mismatch, the final analytic sample also provided adequate statistical power, within the limits of a single-center study, to detect moderate correlations (r ≥0.30) between the MI and quality-of-life outcomes at a significance level of 0.05. Symptomatic load was quantified with the Edmonton Symptom Assessment Scale–Revised (ESAS-r; total score 0–100), a validated scale for evaluating multidimensional symptom burden common in CKD and dialysis populations.^2,7 Psychosocial distress was assessed via the Hospital Anxiety and Depression Scale (HADS), which has been validated by health providers in CKD cohorts,^8-10 and the Distress Thermometer (DT), a brief global distress screening tool validated across multiple oncology and chronic disease populations.^11,12 The HADS instrument includes separate subscales assessing anxiety and depressive symptoms, allowing evaluation of psychological distress components that may independently influence overall emotional stress. HADS and DT scores were rescaled to a 0–100 range and then summed without weighting to yield a composite Psychosocial Distress Score. This composite score was used pragmatically for the purposes of this exploratory analysis and has not been formally psychometrically validated. The MI, defined as Psychosocial Distress Score minus Symptom Burden Score, assessed the discrepancy between emotional distress and physical symptoms. Values >+10 were considered psychosocial-dominant mismatch, values <−10 reflected symptom-dominant mismatch, and values between −10 and +10 indicated approximate concordance between symptom burden and psychosocial distress. The ±10 threshold was selected a priori as an exploratory cut-point representing a clinically interpretable 10% deviation on the standardized 0–100 scale. This threshold was also broadly consistent with approximately half a standard deviation in the observed score distribution, thereby reducing the likelihood that minor score fluctuations would be classified as a mismatch. These cut-offs were chosen for descriptive subgrouping, have not been optimized using diagnostic accuracy methods, and should therefore be interpreted as exploratory rather than definitive.

MI construct validity was assessed in relation to constructs of Kidney Disease Quality of Life (KDQOL-36) and coping styles. The KDQOL-36 is a validated kidney disease-specific QoL scale and has been associated with hospitalization and mortality in dialysis populations.^13,14 Coping style was categorized as resigned, avoidant, and adaptive based on a checklist based on the established coping factors of CKD and dialysis studies.^15,16

Research staff were trained to collect data with standardized guidelines, using a private setting in order to minimize social desirability bias. To ensure data quality and scoring accuracy, 10% of completed questionnaires were randomly selected and independently reviewed by a senior investigator from the department not involved in the primary data collection or participant recruitment. The reviewer verified scoring accuracy and consistency of data entry. Forms reporting ≤10% missing items were replaced using mean data entry within the subscales; forms with >20% missing data were excluded. The match between CKD stages, dialysis status, gender, age categories (<60 vs. ≥60), diabetes situation, and coping strategies, and the lack of a mismatching pattern was analyzed by subgroup. The thresholds used to describe hidden distress and resigned coping patterns were selected as exploratory descriptive cut-points to identify clinically interpretable subgroups and were not intended to represent validated diagnostic thresholds. They should be viewed as a starting point for future work rather than fixed criteria.

All analyses were conducted using SPSS version 26. Continuous variables were summarized as mean ± standard deviation, and categorical variables as frequencies and percentages. Comparison of groups between groups was performed based on independent t-tests, ANOVA, Mann-Whitney U, or Chi-square. Effect sizes (Cohen’s d) and 95% CI were reported. Pearson or Spearman correlation coefficients assessed associations between MI, symptom burden, distress, and KDQOL scores. Independent predictors of KDQOL score, such as MI, symptom burden, age, gender, diabetes, and dialysis status, were determined using multivariable linear regression. Model assumptions were confirmed; variance inflation factors were <2.0, confirming the absence of multicollinearity, and residual plots demonstrated normality and homoscedasticity. At p <0.05, statistical significance was established. Ethical approval for this study was obtained from the Institutional Review Board at Mahatma Gandhi Medical College and Hospital, Jaipur (#4052, dated 31/7/2024), and this work followed the Declaration of Helsinki (2013). Participants reporting clinically significant distress (HADS >15 or DT ≥6) were referred for either psychological or palliative care evaluation.

Results

A total of 150 patients were screened for eligibility. Sixteen were excluded due to ineligibility or refusal to participate, resulting in 134 enrolled participants. Seven questionnaires (5.2%) contained more than 20% missing data and were excluded from analysis. The final analytic sample comprised 127 patients.

Baseline demographic and clinical characteristics are presented in Table 1.

The cohort represents a clinically typical CKD-ESKD population, with substantial comorbidity and representation across disease stages.

The mean ESAS-r symptom burden score was 42.9 ± 18.1. The composite psychosocial distress score (HADS + DT) averaged 51.1 ± 20.7. Stage-wise comparisons have been shown in Table 2.

Patients in CKD stages 3–4 demonstrated significantly higher psychosocial distress relative to symptom burden (large effect size), whereas patients with ESKD exhibited greater symptom burden with comparatively lower distress scores. These findings indicate stage-dependent divergence between symptom intensity and emotional distress.

Overall mismatch prevalence was 63.0% (80/127; 95% CI: 54.4–70.9%). Concordant patterns were observed in 37.0% (95% CI: 29.1–45.6%). Psychosocial-dominant mismatch occurred in 34.6% (95% CI: 26.6–43.5%), and symptom-dominant mismatch in 28.3% (95% CI: 20.9–36.8%).

The overall distribution of mismatch categories has been illustrated in Figure 1, demonstrating that positive and negative mismatches together accounted for nearly two-thirds of the cohort.

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Figure 1: Mismatch type distribution.

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Stage-wise distribution of mismatch patterns has been presented in Table 3 and illustrated in Figure 2. Psychosocial-dominant mismatch predominated in CKD stages 3–4, whereas symptom-dominant mismatch was more frequent in ESKD.

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Figure 2: Stage-wise positive vs negative mismatch. Bar chart comparing mismatch patterns across CKD 3-4, CKD 5 ND, and ESKD. Positive MI predominates early; negative MI increases with disease severity.

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Early CKD stages were characterized by psychosocial-dominant mismatch, whereas ESKD was predominantly associated with symptom-dominant mismatch.

Bar chart with counts of Positive MI, Concordant, and Negative MI. Positive and negative mismatches together represent 63% of the cohort.

Hidden distress and resigned coping.

Hidden distress (ESAS < 30 and Distress > 60) was identified in 15.7% (20/127; 95% CI: 10.0–23.4%) of participants. Resigned coping (ESAS > 55 and Distress < 40) was observed in 13.4% (17/127; 95% CI: 8.3–20.8%).

These subgroups represent potentially clinically meaningful patterns that may not be identified through symptom assessment alone and warrant further study in larger and longitudinal cohorts. Associations between MI, symptom burden, psychosocial distress, and KDQOL scores are presented below. The Mismatch Index demonstrated the strongest negative correlation with QoL, exceeding the strength of association observed for symptom burden or distress individually. The mismatch index showed the strongest correlation with KDQOL scores [Table 4].

Table 4: Correlation of mismatch index, symptom burden, and psychosocial distress with KDQOL scores.

Variable vs KDQOL	R	95% CI	p value
Mismatch Index	–0.47	–0.59 to –0.33	<0.001
Symptom Burden	–0.32	–0.46 to –0.17	0.001
Psychosocial Distress	–0.40	–0.53 to –0.25	<0.001

A multivariable linear regression model was constructed to identify independent predictors of KDQOL score after adjusting for age, gender, diabetes, and dialysis status. In multivariable regression analysis, the mismatch index remained an independent predictor of reduced QoL [Table 5].

Table 5: Multivariable linear regression analysis predicting KDQOL scores.

Predictor	Β	95% CI	p value
Mismatch Index	–0.42	–0.57 to –0.28	<0.001
Symptom Burden	–0.27	–0.43 to –0.10	0.005
Dialysis status (ESKD)	–0.17	–0.31 to –0.02	0.029
Age	–0.05	–0.18 to 0.09	0.46
Sex	–0.06	–0.20 to 0.08	0.39
Diabetes	–0.03	–0.15 to 0.10	0.62

The Mismatch Index remained the strongest independent predictor of reduced QoL after adjustment, indicating that discordance between symptoms and distress contributes independently to patient-reported outcomes.

The distribution of MI values across participants has been shown in Figure 3, demonstrating substantial variability across both positive and negative ranges, consistent with heterogeneity in distress–symptom relationships.

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Figure 3: Mismatch index histogram.

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Histogram of MI values across 127 participants using uniform bin ranges. Distribution shows substantial spread on both positive and negative sides, supporting heterogeneity in distress-symptom relationships.

Additional analyses showed that resigned coping was strongly associated with negative mismatch patterns (∼69%, p <0.001), whereas adaptive coping was more commonly associated with concordant symptom–distress patterns. Female participants had higher rates of psychosocial-dominant mismatch (p = 0.044), and individuals aged ≥60 years were more likely to demonstrate symptom-dominant mismatch.

Discussion

The SPMI highlights clinically meaningful discordance between physical symptom burden and emotional distress in patients with CKD and ESKD. Almost two-thirds of those interviewed showed a mismatch, indicating that symptom intensity in isolation does not necessarily reflect the wider psychosocial experience of kidney disease reliably. Our data demonstrate the case for cognitive-affective decoupling, a phenomenon reported in chronic illness in which emotional processing and somatic appraisal diverge in such a way that the psychological expression and/or suppression would give rise to an unbalanced expression of emotion or suppression of emotion. Such decoupling has been theorized in models of emotional regulation and illness adaptation,^16,17 yet has not previously been operationalized in nephrology populations.

Clinically, discordance between symptom burden and emotional distress suggests differences in illness appraisal, coping adaptation, and social context, not just in disease severity. Psychosomatic medical work has previously found that subjective perception of disease correlates strongly with patient-reported outcomes as strongly as objective assessment of symptom burden, particularly in chronic diseases, in which uncertainty and treatment dependence are salient.^17,18 Indeed, this distinction may be particularly relevant to CKD populations as patients often have long disease trajectories characterized by variable symptoms and evolving psychological adjustment. Quantifying this divergence through a structured index such as the MI may therefore give clinicians an additional lens to interpret the patient’s experiences and identify individuals whose psychosocial needs may otherwise remain under-recognized.

The instruments used in this study capture complementary dimensions of the patient experience in CKD. Multidimensional symptom burden, such as fatigue, pain, nausea, dyspnoea, sleep disturbance, and general well-being, is measured by the ESAS-r, which captures symptoms that are commonly reported in populations with CKD. Psychological symptoms of anxiety and depression are assessed by the HADS, and emotional distress related to illness, social challenges, or existential concerns is measured with the Distress Thermometer. Because the HADS includes separate anxiety and depression subscales, the psychological component of distress in this study reflects both affective dimensions that may independently influence emotional stress in patients with CKD. The KDQOL-36 assesses a disease-specific QoL based on symptom burden, effects of kidney disease on daily activities, and perceived disease burden. However, the strong association between the MI and KDQOL indicates that discordance between physical symptoms and emotional distress may be influencing patients’ perceived QoL more than simply the severity of symptoms.

Prior work has demonstrated patient–clinician discordance in symptom assessment in CKD populations.¹⁹ Symptom burden in ESRD remains under-recognized despite its high prevalence.²⁰

The identification of apparent stage-related differences in mismatch patterns is a key exploratory finding of our study. Accordingly, we view these stage-related findings as hypothesis-generating rather than as evidence of a deterministic effect of CKD stage on mismatch patterns. The patients with CKD stages 3–4 most commonly exhibited psychosocial-dominant mismatch, with relatively little burden of symptoms, but higher emotional distress. Early CKD is often accompanied by prognostic uncertainty, anticipatory anxiety and role disruption, and fear of progression of the disease,^4-6,21 things that may amplify emotional distress separate from physical symptoms. In contrast, those on dialysis were significantly more likely to demonstrate symptom-dominant mismatch, in line with resigned or suppressive coping. Exposure to long-term dialysis was shown to correlate with emotional adaptation, stoicism, and lower levels of overt distress reporting despite high symptoms.^7-9,16 This mirrors the trend observed in oncology and heart failure cohorts, where advanced stages of disease commonly are followed by emotional blunting or avoidant coping characterized by a mismatch between symptom intensity and reported distress.^11,12,22,23

Taken together, these findings suggest that mismatch may be clinically relevant rather than purely descriptive. The strong association between the mismatch index and KDQOL observed in this study suggests that it is not merely the severity of symptoms or distress alone, but their discordance, that may most significantly influence patient-reported outcomes. This divergence may reflect disruptions in how patients internally process and reconcile physical and emotional experiences, potentially impairing adaptive coping mechanisms. Emotional symptom mismatch has also been associated with adverse outcomes such as hospital readmissions in chronic disease populations.²⁴ These findings support the clinical relevance of evaluating mismatch as a distinct construct rather than relying solely on symptom burden or psychosocial distress independently.

In CKD, previous studies have demonstrated that discordance between clinical markers and patient-reported experience correlates with poor health status and well-being.^13,16 Our work extends this notion to propose that discordance within the patients’ self-reported domains also implies prognostic influence within the patient-reported domains of QoL. The presence of hidden distress (15.7%) and resigned coping (13.4%) further demonstrates the clinically vulnerable segments likely to go undetected unless they are assessed through symptom-focused assessment only. Depression and anxiety are often overlooked in CKD, and prevalence estimates are around 40–45% in some individual groups.^8-10 But underreporting of emotional distress has not been the focus. Emotionally suppressed and passive resignation have been reported in dialysis and correlated with poorer psychological adjustment in the long term.^15,16

The MI provides a structured way to summarize both relatively ‘over-expressed’ and ‘under-expressed’ distress states in relation to symptom burden. The broader pattern of discordance between symptom burden and emotional appraisal has been documented in oncology,^11,12 heart failure,²² and chronic pain,^25-27 and our findings suggest that a similar phenomenon may be relevant in nephrology, although further work is needed to confirm its prognostic and clinical significance.

A potential implication is that, if supported by further studies, mismatch assessment could be incorporated into nephrology practice to help prioritize psychosocial assessment. Because the MI can be calculated from instruments already used in many CKD and dialysis settings, it might eventually offer a pragmatic way to flag patients who could benefit from more detailed psychosocial evaluation, particularly in high-volume or resource-constrained units. Emerging evidence from CKD and palliative care indicates that early psychosocial intervention can lead to improved QoL, treatment adherence, and depressive symptoms.^28-31

A number of limitations need to be considered. Cross-sectional design precludes making causal inferences and does not represent time-variable mismatch patterns. The MI was one of the derived indices and is still in need of validation from the outside in the context of several population groups and cultures. Sociocultural norms may also impact how we express our emotions, especially in the Indian context when distressing events are reported. As a last point, the use of self-report instruments may have introduced response bias, but standardized administration and privacy measures were in place to reduce the potential for response bias. Future studies should investigate how mismatch patterns are maintained over time and if such mismatches are predictive of long-term outcomes (hospitalization, dialysis withdrawal, nonadherence, and/or death). Prospective multicenter studies would improve generalizability and help refine clinically meaningful mismatch thresholds. Intervention trials in newly identified mismatch subgroups would inform whether changing discordance would enhance QoL or clinical outcomes.

However, the association between mismatch patterns and CKD stage should be interpreted cautiously, as emotional responses to chronic illness are shaped by multiple factors, including coping style, social support, health literacy, and socioeconomic context, rather than disease stage alone.

Most socioeconomic factors that may affect psychological distress were not systematically collected by the present study, such as education level, income status, rural or urban background, and mechanisms of treatment funding. The study was performed in a tertiary-care teaching hospital, but differences between public and private healthcare settings were not specifically analyzed. These variables could affect symptom perception, coping patterns, and distress reporting and warrant research in the domains of symptom–psychosocial relationships in CKD populations in the future.

Clinical trajectory variables, including time since CKD diagnosis, number of prior nephrology consultations, and duration of dialysis exposure, were not systematically assessed. These variables could affect the emotional adaptation to chronic illness and account for differences in distress–symptom relationships at a given time point. Longitudinal studies using these variables might lead to greater precision in matching patterns across the CKD disease course. In addition, the composite psychosocial distress score derived from HADS and the Distress Thermometer has not undergone formal validation as a combined measure and may not fully capture distinctions between anxiety, depression, and global distress.

In conclusion, the SPMI in this study summarized discordance between physical symptom burden and emotional distress in patients with CKD and ESKD. Mismatch was common and appeared to show stage-related patterns, with hidden distress more frequent in earlier CKD and resigned coping more frequent among dialysis patients. In multivariable analyses, the MI was independently associated with kidney disease-specific QoL over and above symptom burden or distress alone. These findings suggest that assessing SPM may help to highlight patient subgroups whose psychosocial needs are not well reflected by symptom scores, but the index and its thresholds require longitudinal validation and external replication before they can inform clinical decision-making.