Quantitative analyses were performed using IBM SPSS 26.0 and PROCESS macro (version 4.2; The Guilford Press). Demographic and clinical characteristics that differed significantly between groups were entered as covariates. Following correlational and multiple regression analyses, moderated mediation was tested using the ordinary least square–based path analysis [39], with 5000 bootstrap resamples after mean-centering continuous variables. Effects were considered significant when the 95% CI excluded 0. Significant interactions were probed using simple slope analyses [40].

Interview data were analyzed using traditional content analysis [41] with NVivo (version 12; Lumivero). Two researchers (a master’s student in psychology and a clinical nurse) independently coded the first 3 transcripts to develop an initial codebook, which was iteratively refined throughout the analysis. To enhance trustworthiness, preliminary themes were reviewed by a psychology professor and a chief nephrologist, and thematic summaries were returned to 3 participants for confirmation.

Both studies were approved by the Ethics Committee of the Department of Psychology at Renmin University of China (IRB 23‐082; December 15, 2023) and by Jiangyin People’s Hospital (2024 Lun Shen Yan 098; May 10, 2024) and were registered with the Chinese Clinical Trial Registry (ChiCTR2500107906; August 20, 2025). Although ethical approval was obtained before recruitment, the trial was registered retrospectively. The registration application was submitted on December 21, 2023, before participant enrollment. However, completion was delayed due to the mandatory administrative review process required for clinical trial registration in China, including prior filing and institutional reviews within the National Medical Research Registry System of the National Health Commission.

Written informed consent was obtained from all participants (and legal guardians, where applicable). All data were anonymized using unique identifiers, encrypted, and stored on secure servers for 5 years after study completion. Participants were able to withdraw at any time without penalty, received free access to the mindfulness program, and received modest financial compensation after completing the assessments.

Data analysis yielded 4 key themes: the psychological experience of demoralization, barriers to the alleviation of demoralization, facilitators of demoralization alleviation, and intervention needs. Sixteen subthemes were identified (Sections S1-S5 in Multimedia Appendix 1). Overall, 12 out of 14 (85.7%) interviewees reported symptoms that impacted their psychological and physical health, ranging from itching and fatigue to insomnia and pain. For example, participant N2 stated, “My skin itches a lot, and I always feel very uncomfortable.” Similarly, participant N4 reported, “After dialysis, I personally feel a bit sluggish, I can’t sleep well, my bones feel slightly deformed, and the soles of my feet hurt so much that I can’t walk.”

Furthermore, 6 out of 14 (42.9%) interviewees expressed the need for psychological interventions that are simple, intuitive, and easy to understand. Participants emphasized a preference for interventions that could be learned independently and practiced at home with minimal cognitive or physical burden. As participant N1 explained, “For mindfulness exercises online, it should be simple and easy to do, without requiring too much extra time and energy.” Similarly, participant N10 remarked, “The exercises you suggest shouldn’t be too complicated. I’m getting older, so if there are videos or pictures, it would be easier for me.” Participant N14 further highlighted concerns about accessibility, stating, “I don’t quite understand what you’re saying, but if someone can teach me, I’d be willing to try. After all, I can’t travel far right now, so learning something at home would be good for me. I just worry that the online materials might be too complicated for me to learn. I haven’t read much, so if it’s too complex, I might not be able to grasp it.” Taken together, these findings indicate that patients experiencing substantial symptom burdens not only face ongoing psychological distress but also express a clear demand for accessible, low-threshold, and home-based psychological interventions to help alleviate demoralization.

In addition to the aforementioned factors, the qualitative interviews revealed that stigma, social isolation, and lifestyle changes acted as barriers to the improvement of demoralization, whereas family support, social support, peer support, and confrontation coping served as facilitators.

This study provides converging evidence from quantitative analyses, qualitative exploration, and an RCT regarding the mechanism underlying demoralization and the effectiveness of a tailored MMI among patients receiving hemodialysis. By integrating convergent results, this study extends the current evidence in 3 important ways. First, it identifies a potential psychological pathway linking symptom burden to demoralization, with trait mindfulness functioning as a potential buffering role. Second, it provides preliminary evidence supporting the effectiveness of a 6-week MMI in reducing demoralization and improving psychological outcomes in an understudied clinical population. Third, this study demonstrates the value of developing patient-tailored digital psychological interventions, showing that mindfulness-based approaches can be adapted to the specific clinical context of hemodialysis.

The findings from study 1 provide important insights into the psychological processes underlying demoralization among patients receiving hemodialysis. Symptom burden was positively associated with demoralization, and this association was partly explained by avoidance coping. These findings are consistent with previous studies [18,19] and the stress system model [34], which suggest that patients’ responses to persistent symptoms may represent a critical psychological pathway linking physical burden to existential distress. For patients receiving hemodialysis, recurrent symptoms, treatment dependency, and uncertainty regarding disease progression may increase psychological distress and reinforce avoidance coping, such as disengagement from illness-related challenges.

Trait mindfulness emerged as a protective factor that attenuated the associations between symptom burden and avoidance coping with demoralization. This finding is consistent with previous research suggesting that mindfulness may enhance psychological flexibility by promoting nonjudgmental awareness of internal experiences and reducing automatic emotional reactions [43,44]. By promoting acceptance and self-distancing, mindfulness may reduce avoidance-based regulation and negative affect [45], thereby buffering the adverse effects of symptom burden and maladaptive coping on demoralization. However, the absence of moderation on the symptom burden-avoidance pathway suggests that mindfulness may be more effective in modifying emotional responses following avoidance coping rather than preventing the initial emergence of avoidance tendencies under chronic stress [46,47]. These mechanism-oriented findings provided the theoretical foundation for the subsequent MMI intervention, highlighting the importance of cultivating mindfulness skills in patients receiving hemodialysis.

Building on the findings of study 1, the RCT in study 2 showed that the MMI was associated with greater reductions in demoralization and symptom burden, as well as greater increases in trait mindfulness and adaptive coping, compared with usual care. These findings are consistent with growing evidence that online MBIs can improve psychological well-being and alleviate emotional distress among people with chronic illness [48]. Usual care, which primarily focuses on biomedical management, may be insufficient to address the psychological consequences of persistent symptoms and long-term treatment dependence [49]. This is particularly important because demoralization involves the loss of meaning, hope, and perceived competence rather than emotional distress alone.

The intervention effects are broadly consistent with the psychological pathways identified in study 1. The observed increase in trait mindfulness and improvement in coping patterns in the MMI group may therefore represent plausible pathways through which the intervention reduced demoralization. Mindfulness practices may help patients notice physical sensations and illness-related thoughts with less judgment and reactivity, thereby reducing reliance on avoidance-based coping. The intervention also incorporated self-compassion-oriented practices, including body scanning and mindful breathing. As self-criticism and hopelessness are closely related to demoralization, self-compassion may have complemented the mindfulness and coping-related processes described above [50,51]. For patients receiving hemodialysis, who may experience bodily loss of control and treatment-related dependence, these practices may facilitate a more accepting and less self-critical relationship with their bodies.

Beyond intervention efficacy, this study supports the feasibility of delivering mindfulness-based psychological support through a mobile platform for patients receiving hemodialysis. Although traditional mindfulness programs can be effective [28], their implementation may be challenging because of dialysis schedules, physical fatigue, transportation burden, and limited access to psychological services [29]. In contrast, the mobile-based format allowed patients to complete brief daily practices at their convenience, thereby reducing these logistical barriers. Informed by qualitative findings, the intervention used brief videos and easy-to-understand text-image materials to meet patients’ preferences for simple, low-threshold, and accessible psychological support [52]. In addition, the WeChat-based peer support component may have further enhanced engagement and psychological benefits. Previous research has suggested that peer and social support can improve psychological adjustment among individuals with chronic illnesses [53,54] by reducing isolation [55] and strengthening perceived support [56]. Thus, combining structured mindfulness practice with patient-centered digital delivery and peer interaction may provide a practical approach to integrating psychosocial care into routine dialysis management.

Despite these strengths, the study has some limitations. First, the absence of an active or attention-matched control group means that the specific efficacy of the mindfulness components cannot be fully distinguished from nonspecific effects, such as general clinical attention and expectancy. Future studies should use active control conditions or dismantling designs to isolate the unique effects of the mindfulness modules. Second, while peer interaction via the WeChat group was designed to enhance engagement [57], it introduced a potential confounding cointervention. Because the intensity and quality of this peer interaction were not systematically measured, we could not separate the psychological benefits of social/peer support from those of pure mindfulness practice. Future studies should incorporate structured peer-support protocols and objective interaction indicators to clarify the relative contribution of the peer component. Third, the short follow-up period and reliance on self-reported outcomes limited the assessment of the durability and broader clinical impact of the intervention [58]. Future studies should include longer follow-up assessments [59,60] and incorporate clinician-rated, behavioral, or other objective measures to evaluate the maintenance and robustness of intervention effects. Fourth, adherence was assessed using check-in completion because the platform could not capture objective engagement indicators; however, this may not fully reflect actual intervention use. Moreover, early attrition occurred during the second week, mainly due to the burden of daily practice during dialysis days or periods of fatigue. Future digital interventions should incorporate automatic behavioral tracking and adaptive adherence strategies to better capture engagement and accommodate patients’ fluctuating physical conditions.

This study provides evidence that a theory-informed, hemodialysis-specific, MMI can effectively reduce demoralization and improve psychological outcomes among patients receiving long-term dialysis. By integrating converging evidence, this study extends current knowledge on digital psychological interventions by highlighting the potential of patient-tailored mindfulness approaches to address the psychological consequences of chronic disease beyond routine biomedical management. The findings highlight the potential of scalable mobile-based interventions to support the integration of psychosocial care into nephrology practice, particularly for populations facing barriers to accessing traditional psychological services. Future research should examine the long-term effectiveness, implementation strategies, and cost-effectiveness of integrating digital psychological care into routine chronic disease management.