Association between negative emotional states, self-regulation skills, and immunosuppressive medication adherence in liver or kidney transplant recipients: a cross-sectional study

Abstract

Aim

This study aimed to assess the relationship between negative emotions, self-regulation skills, and immunosuppressive medication adherence in liver or kidney transplant recipients, as well as to identify predictors of negative emotional states.

Background

Solid organ transplantation is a crucial and life-saving procedure; however, it presents significant physical, psychological, and social challenges for recipients. Negative emotional states (NESs) including depression, anxiety, and stress are frequently observed among liver or kidney transplant recipients. These emotional difficulties can impact their self-regulation abilities and adherence to immunosuppressive medications, ultimately affecting post-transplant outcomes.

Methods

A cross-sectional study of 221 liver or kidney transplant recipients (3 to 18 months post-transplant) was conducted at a tertiary hospital in Tehran, Iran. Data were collected through phone interviews using the DASS-21, SSIt, and BAASIS scales. The study followed the STROBE checklist for reporting and utilized descriptive statistics, correlation analyses, and linear regression for data analysis.

Results

A moderately strong negative correlation was found between self-regulation skills and NESs (r = -0.68). Poor adherence to immunosuppressive medication was at 23.1%, mainly due to timing non-adherence and missed doses. Regression analysis indicated that younger age, comorbidities, less success and more setbacks in self-regulation skills predicted higher NESs (R² = 0.528). Medication adherence had no significant association with NESs and self-regulation.

Conclusion

Negative emotional states are moderately prevalent among transplant recipients and are frequently associated with difficulties in self-regulation, younger age, and various health conditions. Interventions that offer psychological support, provide training in self-regulation, and address socioeconomic barriers have the potential to enhance emotional well-being and improve post-transplant outcomes.

Introduction

Solid organ transplantation is a life-saving treatment for patients with end-stage organ failure [1]. Kidney transplants are the most common, followed by liver, heart, and lung transplants [2]. Post-transplant patients may face various physical, psychological, and social challenges that adversely impact their health status [3, 4]. Negative emotional states (NESs)—including depression, anxiety, and stress—are particularly prevalent among liver and kidney transplant recipients, significantly influencing their quality of life and overall post-transplant outcomes [5–7]. While these emotional states exhibit distinct characteristics, their overlapping nature necessitates a comprehensive management approach [8, 9]. Self-management skills—patients’ active involvement in managing their health, including medication adherence and lifestyle modifications—are crucial in addressing post-transplant issues [10, 11]. However, a complex interplay exists between NESs and self-management capabilities, as anxiety and depression symptoms can hinder these strategies [12]. Conversely, effective self-management can alleviate NES symptoms, creating a reciprocal relationship that warrants careful examination [12].

To perform self-management successfully, individuals need self-regulation skills, which involve managing thoughts, emotions, and behaviors to achieve personal goals [13, 14]. According to self-regulation theory, this process includes goal setting, active pursuit, and maintaining or adjusting goals as necessary [15]. After transplantation, patients often struggle with these skills due to various challenges, hindering their goal-setting and planning capabilities. Assessing self-regulation skills is essential for practical support and improving health-related quality of life in organ transplant recipients [14]. Understanding the factors contributing to goal success or failure can provide critical insights into patient management [14]. Research indicates that environmental demands, including physiological and psychological stressors, can affect cognitive functions related to self-regulation [16]. Improved self-regulation is linked to reduced negative emotional effects and enhanced overall functioning [17, 18]. However, excessive focus on self-regulation may lead to increased self-criticism, potentially exacerbating NESs [13, 17, 18]. Thus, understanding the relationship between NESs and self-regulation skills is crucial for identifying factors that influence patients’ ability to manage their conditions effectively [19, 20].

Adherence to immunosuppressive medication is vital for the long-term success of organ transplantation [19, 20]. Non-adherence can lead to graft rejection and failure, significantly impacting patient outcomes [21, 22]. Alarmingly, studies show that 20% to 70% of organ transplant recipients do not follow treatment recommendations [22–27]. Medication adherence is a dynamic process requiring ongoing monitoring and integration into daily clinical management [5, 27, 28]. Despite recognizing the importance of NESs, self-regulation skills, and medication adherence in transplant recipients, few studies have explored their interrelationships. Some research indicates a significant negative correlation between NESs and self-management in post-transplant patients [6, 29–31]. However, most existing research on self-regulation has focused on younger populations, with limited examinations in organ transplant recipients [15, 32, 33]. Given the necessity of these skills for goal-setting post-transplant, further exploration could enhance understanding of patient outcomes and quality of life.

Moreover, previous research suggests that the relationship between NESs and medication adherence varies by transplanted organ type and population, leading to inconsistent findings [5, 34–36]. For instance, studies on liver or kidney transplant recipients have found correlations between NESs and lower medication adherence [5, 34], while others report no significant relationship [36]. Interestingly, a survey of lung transplant recipients indicated that higher anxiety levels were associated with better medication adherence [35].

Given these discrepancies and significant gaps in the literature, this study aims to investigate the complex relationships among NESs—specifically depression, anxiety, and stress—self-regulation skills, and adherence to immunosuppressive medication in liver or kidney transplant recipients. The research questions will clarify the influences of NESs on self-regulation and medication adherence, aiming to identify potential predictors of NESs within this population. The anticipated outcomes are expected to provide valuable insights into the factors influencing post-transplant health outcomes, ultimately enhancing individuals’ quality of life and overall health status following organ transplantation.

Methods

Design and setting of the study

A descriptive cross-sectional study was conducted at the Imam Khomeini Hospital Complex (IKHC), which is affiliated with the Tehran University of Medical Sciences (TUMS), from June 27 to November 2, 2024. This study aimed to investigate the association between negative emotional states, self-regulation skills, and adherence to immunosuppressive medication among the hospital’s discharged patient population. By focusing on these interrelated factors, the research seeks to provide insights into how emotional well-being and self-management capabilities influence medication adherence in transplant recipients. Additionally, convenience sampling was utilized in this study, which may introduce potential bias. This limitation should be acknowledged, as it may affect the generalizability of the findings to the broader population of transplant patients. The study followed STROBE guidelines to improve transparency and quality in observational research. Data was collected through patient interviews and medical records for reliable analysis.

Participants and data collection

Convenience sampling was utilized due to logistical constraints and the necessity for rapid data collection in a single-center setting (IKHC, Tehran). Eligible patients were identified from a list of liver and kidney transplant recipients attending clinics at IKHC, and they were recruited through voluntary participation following an informative briefing about the study. While this method facilitated timely data gathering, it may limit the sample’s representativeness, potentially over-representing patients with regular clinic follow-ups or those who are more accessible by phone. Recognizing this limitation, future studies could benefit from implementing stratified sampling to ensure adequate representation across transplant types (liver vs. kidney), duration since transplantation, and key demographic characteristics. Data were obtained through phone interviews conducted using a standardized script. Trained researchers entered responses directly into Google Forms to promote consistency and minimize data entry errors. Participants were contacted up to three times to enhance response rates. Interviewers underwent prior training via a brief workshop, which included instruction on the standardized script, techniques to minimize bias (such as avoiding leading questions), and procedures to maintain respondent anonymity while reducing access to identifiable clinical information.

The minimum required sample size was calculated using G*Power software for an independent-samples t-test, with an alpha level set at 0.05 and a desired power of 0.80. An effect size of 0.30 was selected, as it is frequently considered a slight to moderate effect in clinical research, particularly in studies focusing on practical approaches in pre-clinical, clinical, and laboratory settings [37]. The analysis indicated a necessity for 133 participants. Considering a projected attrition rate of 20%, based on previous studies, the adjusted minimum sample size was set at 200 participants to ensure adequate power for the study. Ultimately, a total of 221 patients were enrolled, all of whom had undergone liver or kidney transplantation and were monitored from the beginning of month 3 through the end of month 18 post-transplantation. A post-hoc power analysis recalculated for the final sample size of 221 participants indicated a power of 0.82, thereby confirming that the sample size was sufficient to detect the hypothesized effect size. While the final sample size of 221 exceeded the initial target, enhancing the precision of our estimates by reducing the standard error and increasing the confidence intervals, we recognize that larger samples may yield statistically significant results for minimal effects. Thus, we emphasize the importance of interpreting our findings in terms of both statistical significance and clinical relevance, especially in relation to the observed effect sizes.

Inclusion and exclusion criteria

Participants must be at least 18 years old and recipients of liver or kidney transplants discharged from IKHC Hospital. They should be willing to participate and able to communicate effectively with the researcher. Participants must demonstrate stable physical, mental, and cognitive status, verified by medical records. Those with acute health issues in the past month, such as severe infections or transplant rejection, will be excluded. Additionally, individuals hospitalized for complications, those with a history of psychological disorders, or those who have used antidepressants will not be eligible. Stable status is defined as no hospitalizations or acute complications in the past month.

Instruments

Data were collected using a clinical and demographic information form, the Self-Regulation Skills Instrument in Transplantation, the Basel Assessment of Adherence to Immunosuppressive Medications Scale, and the Depression Anxiety Stress Scale-21. Further details about these tools are provided below.

Clinical and demographic information form

Clinical data and sociodemographic factors were collected through phone interviews and medical records. A researcher-developed questionnaire gathered information on age, gender, education, income level, marital status, immunosuppressive regimen, underlying liver disease, and comorbidities. Comorbidities included hypertension, diabetes, and heart disease for all participants, as well as renal diseases in liver transplant recipients and liver diseases in kidney transplant recipients.

The self-regulation skills instrument in transplantation (SSIt)

The SSIt was developed by Zanten et al. in 2023 to create a self-management tool for organ transplant recipients that encompasses self-regulation skills [14]. SSIt is a new 21-item self-report questionnaire divided into two scales: ‘Setbacks’ and ‘Successes.’ The items are on a five-point Likert scale from 1 (strongly disagree) to 5 (strongly agree) for the ‘Successes’ scale and conversely for the ‘Setbacks’ scale. The total score ranges from 21 to 105, with higher scores indicating better self-regulation skills. In the study by Zanten et al., the validity and reliability of this tool for assessing the necessary skills for self-regulation after transplantation were confirmed [14].

The study began by securing permission from the original developers of the questionnaire to uphold intellectual property rights. Once this crucial step was completed, we moved on to the translation process, which involved rigorous forward and backward translations in both Persian and English. These translations were conducted by two bilingual language specialists who are proficient in both languages and knowledgeable about the subject matter.

We conducted a comprehensive evaluation of both face validity and content validity by incorporating feedback from 12 esteemed nursing faculty members and various field experts. The Persian version of the SSIt was pilot-tested with 20 transplant recipients to assess its cultural relevance. Based on their feedback, we made minor wording adjustments. The diverse insights gathered contributed to the overall quality of the questionnaire content. Consequently, the development team achieved a Content Validity Index (CVI) of 0.92, which indicates strong agreement among experts regarding the relevance of the items. Additionally, the Content Validity Ratio (CVR) was 0.93, reflecting a high level of consensus on the necessity of each item.

These metrics validate the thorough and reliable development process, supporting the validity and applicability of the SSIt in its intended context. Zanten et al. [14] reported Cronbach’s alpha coefficients of 0.90 for the “Setbacks” scale and 0.89 for the “Successes” scale, with moderate Spearman correlations between the subscales and the Health Education Impact Questionnaire (heiQ) at 0.55 and 0.46, respectively. In our study, the Persian version of the questionnaire demonstrated a Cronbach’s alpha of 0.95.

Basel assessment of adherence to immunosuppressive medication scale (BAASIS)

The Leuven-Basel research group developed the BAASIS following the taxonomy of medication adherence, which defines adherence as “the process by which patients take their medication as prescribed.” This taxonomy divides adherence into three measurable phases.: initiation, implementation, and persistence [38]. The latest version of the BAASIS (2020 and beyond) consists of a 5-item questionnaire that measures adherence to immunosuppressive medications: implementation in the past 4 weeks (items 1a: Taking, 1b: Drug holidays, 2: Timing, and 3: dose reduction), persistence/discontinuation in the past year (item 4), and initiation of any new medication in the past year (item 5) [38]. Non-adherence to medications refers to any deviation from prescribed medication regimens. In this study, we utilized the BAASIS interview version, which was adapted for phone administration. The adaptation involved structuring questions to minimize leading prompts, and interviewers received training to maintain neutrality throughout the process. Both the written self-report and interview versions of the BAASIS consist of the same items, although the wording differs slightly based on the mode of administration [39, 40]. To further ensure the accuracy of responses, we cross-checked the participants’ answers with their medical records where possible. Psychometric analyses indicate that the BAASIS is a valid and reliable self-report tool for assessing medication non-adherence in organ transplant recipients [39, 40]. For future studies, we recommend considering the use of both self-report and interview versions to compare reliability.

Depression anxiety stress scale-21 items (DASS-21)

The DASS-21 is a screening instrument designed to assess levels of depression, anxiety, and stress. This valid questionnaire has been extensively utilized across various populations and fields because of its effectiveness in evaluating multiple adverse mental health conditions. The scale posits that depression, anxiety, and stress collectively form a general distress construct despite their unique characteristics [41]. The updated brief version of the DASS consists of 21 items divided into three subscales, each containing seven items. Responses are measured on a four-point Likert scale, where participants score each item from 0 (does not apply to me at all) to 3 (applies to me most of the time). The maximum score for each subscale is 21, with higher scores indicating more significant psychological distress. In the original study, the DASS-21 demonstrated high reliability, with Cronbach’s alpha coefficients of 0.91 for depression, 0.84 for anxiety, and 0.90 for stress [42]. The severity levels for the Depression Anxiety Stress Scales (DASS-21) were determined based on the cut-off scores established in the Lovibond study and by Sahebi et al. [42, 43]. These levels are defined as follows: Anxiety: normal (0–7), mild (8–9), moderate (10–14), severe (15–19), and very severe (above 20); Depression: normal (0–9), mild (10–13), moderate (14–20), severe (21–27), and very severe (above 28); Stress: normal (0–14), mild (15–18), moderate (19–25), severe (26–33), and very severe (above 33). Previous research has demonstrated robust psychometric properties for the Persian version of the DASS-21, supporting its utility in the assessment of depression, anxiety, and stress [41, 43].

Statistical analysis

Data analysis was conducted using SPSS version 27 software to facilitate a comprehensive statistical evaluation. Descriptive statistics were employed to characterize the data, presenting means alongside standard deviations for continuous variables and frequencies with percentages for categorical variables. Independent t-tests were utilized to compare means between two groups, while one-way analysis of variance was applied for comparisons involving more than two groups. Before conducting these tests, the assumptions of normality and homogeneity of variances were thoroughly assessed. The Shapiro-Wilk test was implemented to evaluate the normality of the distribution, and the Levene’s test was performed to check for homogeneity of variances. Given the normal distribution observed, parametric statistical tests were appropriately applied.

Additionally, Pearson correlation coefficients were calculated to determine the strength and direction of relationships between variables. Linear regression analysis was employed to identify potential predictors of outcome variables and to enhance understanding of existing relationships.

In the linear regression model, six adequacy indicators were meticulously examined. Normality was evaluated using the Shapiro-Wilk test, while linearity was assessed through scatter plots and an analysis of residual ranges. The absence of multicollinearity was confirmed by the Variance Inflation Factor (VIF) values, which consistently remained below 5. A significance level of α = 0.05 was established for all analyses to ensure a reliable interpretation of the results. Tolerance values ranged from 0.710 to 0.962, corresponding to VIF values between 1.040 and 1.408, indicating only a slight degree of multicollinearity among the predictors. Furthermore, the Durbin-Watson test statistic was utilized to evaluate autocorrelation in the regression residuals, resulting in a value of 1.995. This statistic spans from 0 to 4, with a value close to 2 indicating the absence of autocorrelation. The findings suggest minimal autocorrelation, reinforcing the independence of the residuals within the regression model.

Results

Table 1 summarizes the general characteristics and clinical data of the participants. A total of 221 organ transplant recipients were enrolled in the present study. Among participants, 54.8% were liver transplant recipients, 40.3% were kidney transplant recipients, and 5% were kidney-Pancreas transplant recipients. The mean age of the participants was 44.42 ± 13.22 years. Of all participants, 65.2% were men, 74.7% were married, and 47.1% had Secondary or Tertiary education. It was found that 33.5% of the participants had one or more comorbidities besides the primary underlying disease. The most commonly used immunosuppressive drugs were Tacrolimus/Mycophenolate mofetil in liver transplant recipients and Tacrolimus/Mycophenolic acid in kidney transplant recipients, respectively.

Table 1.

General characteristics of the participants (n = 221)

Characteristics	N	%	M ± SD
Age			44.42 ± 13.22
18–30 years	35	15.8
31–45 years	82	37.1
46–60 years	70	31.7
61 ≤ years	34	15.4
Gender
Male	144	65.2
Female	77	34.8
Marital status
Single	49	22.2
Married	165	74.7
Widowed or divorced	7	3.2
Education
Primary or no schooling	58	26.2
Secondary- Tertiary	104	47.1
Academic	59	26.7
Income level
Low income	84	38.0
Average income	112	50.7
High income	25	11.3
Transplanted organ
Liver	121	54.8
Kidney	89	40.3
Kidney-Pancreas	11	5.0
Presence of comorbidities
Yes	74	33.5
No	147	66.5
Immunosuppressive agents
Liver
Tacrolimus	109	90.1
Cyclosporine	12	9.9
Mycophenolate mofetil	113	93.3
Mycophenolic acid	4	3.3
mTOR inhibitors	9	7.4
kidney
Tacrolimus	100	100.0
Mycophenolate mofetil	24	24.0
Mycophenolic acid	69	69.0
mTOR inhibitors	5	5.0
BASSIS
Good adherence	170	76.9
Poor adherence	51	23.1

mTOR inhibitors: mammalian (mechanistic) target of rapamycin inhibitors

SD Standard deviation

The results also show that 23.1% of the participants had issues with the implementation phase of BASSIS and exhibited poor adherence to immunosuppressive medications. Among patients with poor adherence, during the past four weeks, 10% had missed the dose of their immunosuppressive medication at least once, 4.1% had skipped two or more doses in a row, 14% had taken their medications more than two hours before or after the dosing time, and 2.7% had changed the prescribed amount of any of anti-rejection medications without telling their doctor. Almost none of the participants reported issues with the initiation or persistence phase of BASSIS.

The participants’ mean self-regulation skills score was 77.67 ± 10.02, and the mean score of their DASS-21 was 12.49 ± 11.07. Table 2 presents additional information regarding the mean and standard deviation of the domains and subscales of the main instruments.

Table 2.

Participants’ mean scores on SSIt, DASS-21, and BAASIS (N = 221)

Variables	M ± SD	Score range	Min.-Max.
SSIt. total	77.67 ± 10.02	21–105	37–103
Successes	42.38 ± 4.22	10–50	16–50
Setbacks	30.71 ± 7.78	11–55	13–52
DASS-21	12.49 ± 11.07	0–63	0–55
Depression	3.37 ± 4.27	0–21	0–20
Anxiety	3.39 ± 3.45	0–21	0–20
Stress	5.71 ± 4.61	0–21	0–21

Table 3 shows the levels of depression, anxiety, and stress among organ transplant recipients. Of all participants in the present study, 15.8% reported mild to extremely severe depression, 15.8% reported mild to severe stress, and 18.6% reported mild to extremely severe anxiety.

Table 3.

Levels of negative emotional states (depression, anxiety and stress) in organ transplant recipients. (n = 221)

Level	Depression N (%)	Stress N (%)	Anxiety N (%)
Normal	186 (84.2)	186 (84.2)	180 (81.4)
Mild	13 (5.9)	13 (5.9)	22 (10.0)
Moderate	12 (5.4)	12 (5.4)	11 (5.0)
Severe	7 (3.2)	10 (4.5)	7 (3.2)
Extremely severe	3 (1.4)	0 (0.0)	1 (0.5)

All percentages may not total 100 due to rounding

Table 4 summarizes the mean scores of the DASS-21 and SSIt based on participants’ characteristics and their adherence to immunosuppressive treatment. The analysis showed that DASS-21 scores were significantly higher among participants with comorbidities (p = 0.041) and those with lower income levels (p = 0.019). In contrast, SSIt scores decreased with lower levels of education (p = 0.025) and income (p = 0.048). Notably, there were no significant differences in the mean DASS-21 and SSIt scores between participants with good adherence to treatment and those with poor adherence. These findings suggest that comorbidities and socioeconomic factors are significantly associated with emotional well-being and self-regulation skills among the participants.

Table 4.

Comparison of organ transplant recipients’ self-regulation skills and negative emotional States (depression, anxiety and stress) according to general characteristics (n = 221)

Characteristics	N	%	DASS-21 (total score)	SSIt
Gender			Mean ± SD	Mean ± SD
Male	144	65.2	11.60 ± 10.30	78.29 ± 9.96
Female	77	34.8	14.15 ± 12.30	76.51 ± 10.09
Test and value			t = − 1.552 p = 0.123	t = 1.259 p = 0.209
Marital status			Mean ± SD	Mean ± SD
Single	49	22.2	12.81 ± 11.02	78.69 ± 11.32
Married	165	74.7	12.18 ± 10.89	77.67 ± 9.61
Widowed or divorced	7	3.2	17.42 ± 15.82	70.57 ± 7.84
Test and value			F = 0.776 p = 0.461	F = 2.031 p = 0.134
Education			Mean ± SD	Mean ± SD
Primary or no schooling	58	26.2	14.37 ± 13.06	74.63 ± 10.53
Secondary- Tertiary	104	47.1	11.32 ± 9.63	78.61 ± 9.50
Academic	59	26.7	12.69 ± 11.26	79.01 ± 9.95
Test and value			F = 1.432 p = 0.241	F = 3.741 p = 0.025*
Income level			Mean ± SD	Mean ± SD
Low income	84	38.0	14.36 ± 12.74	76.22 ± 11.18
Average income	112	50.7	12.08 ± 9.94	77.84 ± 9.13
High income	25	11.3	8.00 ± 8.49	81.800 ± 8.74
Test and value			F = 4.191 p = 0.019*	F = 3.069 p = 0.048*
Presence of comorbidities			Mean ± SD	Mean ± SD
Yes	74	33.5	14.85 ± 12.96	76.59 ± 10.96
No	147	66.5	11.30 ± 9.83	78.22 ± 9.50
Test and value			t = − 2.071 p = 0.041*	t = 1.142 p = 0.255
BASSIS (implementation)			Mean ± SD	Mean ± SD
Good adherence	170	76.9	12.02 ± 10.65	77.72 ± 10.26
Poor adherence	51	23.1	14.05 ± 12.38	77.52 ± 9.27
Test and value			t = − 1.151 p = 0.251	t = 0.121 p = 0.904

SD Standard Deviation, t Independent t-Test, F One-Way Analysis of Variance (ANOVA)

^*p-value < 0.05

The correlation analysis presented in Table 5 shows Pearson correlations between the SSIt domains and the DASS-21 subscales. There was a moderately strong negative relationship between participants’ total SSIt scores and their DASS-21 scores (r = −0.68, p < 0.001). Statistically significant correlations were found between the two SSIt domains—successes and setbacks—and the three subscales of the DASS-21: depression, anxiety, and stress. Specifically, SSIt-successes showed a significant negative correlation with overall DASS-21 score (r = −0.35, p < 0.001). At the same time, SSIt-setbacks demonstrated a significant positive correlation with overall DASS-21 score (r = 0.68, p < 0.001). Also, there were significant negative correlations between SSIt-total and the individual subscales of depression (r = −0.61, p < 0.001), anxiety (r = −0.55, p < 0.001), and stress (r = −0.65, p < 0.001). These findings suggest that higher self-regulation skills are associated with lower levels of negative emotional states among participants.

Table 5.

Correlations between self-regulation skills and negative emotional States in organ transplant recipients (n = 221)

		SSIt. Total	SSIt. successes	SSIt. setbacks	DASS-21. Total	Depression	Anxiety	Stress
SSIt. Total	Pearson Correlation	1
	Sig. (2-tailed)
SSIt. successes	Pearson Correlation	0.681**	1
	Sig. (2-tailed)	0.000
SSIt. setbacks	Pearson Correlation	− 0.918**	− 0.333**	1
	Sig. (2-tailed)	0.000	0.000
DASS-21. Total	Pearson Correlation	− 0.679**	− 0.349**	0.684**	1
	Sig. (2-tailed)	0.000	0.000	0.000
Depression	Pearson Correlation	− 0.607**	− 0.384**	0.572**	0.899**	1
	Sig. (2-tailed)	0.000	0.000	0.000	0.000
Anxiety	Pearson Correlation	− 0.551**	− 0.216**	0.592**	0.853**	0.637**	1
	Sig. (2-tailed)	0.000	0.001	0.000	0.000	0.000
Stress	Pearson Correlation	− 0.655**	− 0.320**	0.669**	0.928**	0.754**	0.708**	1
	Sig. (2-tailed)	0.000	0.000	0.000	0.000	0.000	0.000

^**Correlation is significant at the 0.01 level (2-tailed)

In multiple linear regression analysis, the DASS-21 was taken as the dependent variable, and socio-demographic factors (age, gender, marital status, education, and income level), time since transplantation, comorbidity, two domains of self-regulation skills, and immunosuppressive adherence were taken as independent variables. The results showed that younger age, having comorbidities, less success, and more setbacks in self-regulation skills were the significant predictors of negative emotional states (depression, anxiety, and stress) in liver or kidney transplant recipients, which accounted for 52.8% of the total variation (all p < 0.05) (Table 6).

Table 6.

Multiple linear regression analysis of factors associated with negative emotional States in organ transplant recipients (n = 221)

predictor	Unstandardized Coefficients		Standardized Coefficients	t	p-value	95.0% Confidence Interval for B
	B	SE	β			Lower Bound	Upper Bound
Constant	2.876	7.636		0.377	0.707	−12.177	17.928
Age	−0.116	0.046	−0.139	−2.522	0.012*	−0.207	−0.025
Gender	0.728	1.143	0.031	0.638	0.524	−1.524	2.981
Marital status	−0.379	1.103	−0.018	−0.343	0.732	−2.554	1.797
Education	0.536	0.782	0.035	0.685	0.494	−1.006	2.077
Income level	−1.341	0.842	−0.079	−1.594	0.113	−3.000	0.318
Time since transplantation (days)	−0.001	0.004	−0.013	−0.278	0.781	−0.009	0.007
Comorbidity	3.326	1.165	0.142	2.854	0.005*	1.029	5.624
SSIt (successes)	−0.306	0.139	−0.117	−2.201	0.029*	−0.579	−0.032
SSIt (setbacks)	0.909	0.075	0.639	12.205	0.000*	0.763	1.056
BASSIS (implementation)	1.335	1.282	0.051	1.041	0.299	−1.192	3.863

SE Standard error

R² = 0.528, Adjusted R² = 0.506, F = 23.503, P < 0.001, Durbin Watson = 1.995

^*Significant predictor (p < 0.05)

Discussion

This research is essential due to the challenges faced by solid organ transplant recipients, which are significantly associated with their quality of life and recovery. Post-transplant patients often deal with interconnected physical, psychological, and social issues [44]. Factors such as medication adherence and postoperative complications contribute to these challenges [5, 45]. Additionally, recipients may experience anxiety and depression, affecting recovery and outcomes [5–7, 45]. Despite existing literature, gaps remain in understanding the relationships among NESs, self-regulation skills, and medication adherence. This study aims to assess these relationshipsas well as to identify predictors of negative emotional states (NESs) among liver or kidney transplant recipients to enhance patient outcomes and quality of life.

In our study of liver or kidney transplant recipients, 15.8% reported mild to very severe depression and stress, while 18.6% experienced mild to very severe anxiety, with a mean DASS-21 score of 12.49 ± 11.07. Excluding individuals with acute health conditions and post-transplant complications may lead to an underestimation of NESs. Significant predictors of NESs included younger age, comorbidities, lower success, and more setbacks in self-regulation, accounting for 52.8% of the variance. Previous studies show varying rates of psychological issues among post-transplant patients, influenced by transplant type and socio-demographic factors. A systematic review by Biyyala et al. [7] reported one-year cumulative prevalence rates of 25% for depression and 29% for anxiety among liver transplant recipients, while Lim et al. [46] found a depression rate of 24.52%, associated with younger age and higher education.

Hu et al. [6] found that 12.5% of kidney transplant recipients experienced anxiety, while 25% faced depression. Uyar et al. [5] reported higher NESs among kidney transplant recipients with chronic illnesses, and Yaban et al. [47] identified age and economic status as predictors of depression. Akbulut et al. [48] highlighted those biliary complications and low income significantly affected depression and anxiety in liver transplant recipients. Thus, addressing socio-economic factors, comorbidities, and post-transplant complications is essential for managing and preventing NESs in these patients.

Patients’ self-regulation is crucial for maintaining health and improving outcomes in post-transplant patients. A study on liver transplant recipients identified health self-management as key to self-regulation and self-care behaviors [49]. Correlation analysis revealed a strong inverse relationship between self-regulation skills and NESs, with significant correlations between the domains of SSIt (successes and setbacks) and the DASS-21 subscales (depression, anxiety, and stress). While much of the literature on self-regulation has focused on health-promoting behaviors in adolescents [15, 32, 33], there is limited information on its association with chronic diseases or organ transplant recipients. Previous studies have explored the associations of self-management and self-efficacy, closely related to self-regulation, with NESs [6, 29, 31].

Hu et al. [6] found that anxiety and depression negatively impacted the psychosocial self-management of kidney transplant recipients. Similarly, Chang-yun et al. [31] reported a negative correlation between self-management and symptoms of anxiety and depression, while noting positive correlations with self-efficacy and self-management support. Weng et al. [29] demonstrated that higher self-efficacy and improved self-care behaviors reduced depressive symptoms among kidney transplant recipients. Milaniak et al. [30] identified social support and self-efficacy as significant predictors of depression and stress in heart transplant recipients. Zaldonis et al. [50] found that lung transplant recipients who scored higher in planning and acting exhibited fewer symptoms of anxiety and depression.

The current study shows that patients with lower education and income levels exhibit poorer self-regulation skills. Numerous studies support the link between socio-demographic factors and self-management behaviors [51–56]. For instance, Zhang et al. [56] found that reduced family support and lower educational attainment negatively impact self-management among liver transplant recipients. Lai et al. [53] noted that addressing depression and improving educational opportunities can enhance self-management and self-efficacy in patients with pre-end-stage renal disease. Limited income and education restrict access to mental health resources, highlighting the need for affordable, community-based interventions like group counseling and mobile apps. Strategies should include subsidized psychological support and educational programs to improve self-management. Providing emotional support for low socioeconomic patient’s post-transplant may enhance self-regulation and outcomes. Future research should consider socioeconomic barriers’ impact on health outcomes.

The utilization of immunosuppressive agents is essential for organ transplant recipients, significantly influencing disease outcomes and graft survival [19, 20]. Non-adherence to these medications heightens the risks of graft rejection, readmission, mortality, and increased healthcare costs [28, 57]. In this study, the most frequently prescribed agents were Tacrolimus/Mycophenolate mofetil for liver transplant recipients and Tacrolimus/Mycophenolic acid for kidney transplant recipients. The results revealed that 23.1% of participants demonstrated poor adherence, primarily due to timing issues—14% took their medication more than two hours early or late, while 10% missed doses in the past month. This rate of non-adherence is consistent with estimates from other studies for liver transplant recipients (ranging from 15% to 40%) [19, 23]. However, it is lower than the general population rate of approximately 50% [21] and broader estimates for kidney transplant recipients (20% to 50%) [22, 24–26, 58–60]. Variations in adherence rates across different studies may be ascribed to differences in settings, populations, or measurement tools. Future research would benefit from a meta-analysis to better contextualize these findings within the existing literature on adherence to immunosuppressive medications.

Most studies have used the BASSIS to assess adherence to immunosuppressive medication [22–24, 59]; however, some studies have utilized other tools as well [19]. In the study by Liu et al. [58] on kidney transplant recipients, 12.97% of patients reported altering their prescribed immunosuppressive agent dosage without their physician’s permission, which was the most common behavior among patients. In another study by Zhu et al. [22], failure to adhere to medication timing was the most prevalent reason for non-compliance with immunosuppressive medication, with the highest rate of 27.8%. The second most common problem was missing a dose of an immunosuppressive agent, with a rate of 21.6%. Also, in the study by Chen et al. [24], failure to adhere to timing was the most frequent issue (33.3%), followed by non-adherence.

Risk factors contributing to non-adherence to immunosuppressive medication encompass patient characteristics, treatment-related factors, socio-economic and cultural influences, and elements of the healthcare system [21, 28, 58]. it is essential to note the lack of a significant association between medication adherence and two key factors: self-regulation skills and NESs. The study indicated a higher prevalence of negative emotional states (NESs) among patients with poor adherence; however, this difference was not statistically significant. Conversely, Uyar et al. [5] reported a strong negative correlation between anxiety, stress, and adherence to immunosuppressive medication among kidney transplant recipients. In contrast, Kisielska et al. [36] found no significant correlation between depression and anxiety in liver transplant recipients. Notably, Wessels-Bakker et al. [35] discovered that elevated anxiety levels might be linked to better adherence in lung transplant patients, potentially due to heightened medication vigilance resulting from dyspnea. Additionally, Liu et al. [58] established a connection between emotional self-efficacy and adherence, which contrasts with the findings of the current study.

One possible explanation for this discrepancy is the difference in study populations and settings; for example, much of the existing evidence is derived from clinical samples with higher psychological burden, while our participants may have had more stable emotional functioning. In addition, variations in measurement tools and cultural or health-system contexts may account for inconsistent findings. Another interpretation is that psychological factors may exert only indirect effects on adherence, potentially mediated by variables such as social support, illness perceptions, or treatment beliefs. These differences highlight the complexity of adherence behavior and suggest that emotional states and self-regulation might not always play a direct role across all populations. Further research is warranted to clarify under which circumstances these factors significantly influence adherence.

Non-adherence continues to be prevalent among transplant recipients, necessitating ongoing monitoring, particularly during stressful periods [28]. Practical strategies to address unintentional non-adherence include personalized interventions, electronic reminders, and regular follow-up appointments [21, 28]. Additionally, continuous monitoring and motivational-behavioral interventions are recommended to prevent intentional non-adherence [28]. Future studies should incorporate qualitative interviews to investigate cultural barriers and their influence on NESs and medication adherence within Iranian healthcare settings.

Limitations

This study thoroughly evaluates negative emotional states (NESs), self-regulation skills, and immunosuppressive medication adherence among liver and kidney transplant recipients, utilizing validated instruments (DASS-21, SSIt, BAASIS) to enhance the reliability of the findings. The inclusion of both transplant types was intended to provide a broader understanding of the factors influencing medication adherence; however, it is essential to acknowledge that differences between these groups may affect study outcomes. Notably, subgroup analyses to explore variations in NESs and self-regulation skills between liver and kidney transplant recipients were not conducted. This decision was based on the preliminary nature of the study and the aim to maintain a manageable scope of analysis. While the inclusion of diverse transplant types improves generalizability and identifies key predictors such as younger age, comorbidities, and poor self-regulation, several limitations must be acknowledged. The cross-sectional design restricts the ability to draw causal inferences, and convenience sampling, while practical for this study, may introduce selection bias, affecting the representativeness of the sample.

Additionally, phone-based interviews may introduce interviewer bias or response inaccuracies, particularly for sensitive questions related to psychological distress. The reliance on self-reported measures carries the risk of recall bias, and excluding acutely ill patients might lead to an underestimation of the prevalence of NESs. The single-center nature of the study further limits generalizability, while the absence of longitudinal follow-up hinders the ability to track changes over time. To mitigate these issues, future studies should employ mixed methods, incorporating both in-person and phone interviews to validate responses, and consider conducting sensitivity analyses to exclude outliers where feasible. Despite these limitations, the study underscores the necessity for psychological support and self-regulation training in post-transplant care, suggesting that future research should utilize longitudinal, multi-center designs with objective adherence measures to enhance clinical applicability.

Clinical implications

This study highlights the need for targeted interventions to improve emotional well-being and medication adherence among liver and kidney transplant recipients. Nurses should implement brief motivational interviewing during clinic visits, particularly for younger patients with comorbidities, to enhance self-regulation skills. Establishing structured self-regulation training and routine psychological support services can empower patients in managing negative emotional states (NESs). Additionally, health systems should fund telehealth platforms for remote adherence monitoring, especially for low-income patients, and organize educational workshops to promote self-management. Future studies should pilot these interventions to evaluate their effectiveness in improving patient outcomes.

Conclusion

The present study examined NESs, self-regulation skills, and adherence to immunosuppressive medication among liver or kidney transplant recipients. Participants reported a moderate level of NESs, including depression, anxiety, and stress. Predictors of NESs in participants included younger age, presence of comorbid conditions, lower successes, and more setbacks in self-regulation skills. Correlation analysis also revealed a relatively strong and inverse relationship between self-regulation skills and NESs. Self-regulation skills were lower among patients with lower education and income levels than those with higher education and income. Overall, 23.1% of participants exhibited poor adherence to immunosuppressive medication, with the most common issue being noncompliance with medication timing, followed by missing doses of medications at least once. The rate of NESs was higher in the group with poor adherence than in those with good adherence; however, this difference was not statistically significant. Considering socio-economic factors and psychological interventions, such as training in self-regulation skills and self-efficacy, may reduce negative emotional states and subsequently enhance quality of life and improve disease outcomes in transplant recipients. Additionally, measures are needed to improve adherence to the timing of medication intake and prevent forgetting doses of immunosuppressive drugs in transplant recipients.

Authors’ contributions

Study design: M. R. Data collection: M. R and E. G. Data analysis: M. R and A. M. Study supervision: A. M and M. N. Manuscript writing: M. R and A. M.

Funding

No Funding.

Data availability

De-identified datasets that were used or analyzed in this study can be obtained from the corresponding author (A. M.) upon reasonable request, subject to ethics committee approval. For future studies, it is recommended to deposit data in a public repository, such as Dryad, to enhance transparency, if permitted.

Declarations

Ethics approval and consent to participate

This study adhered rigorously to ethical principles outlined by the Declaration of Helsinki and national biomedical research guidelines. Ethical approval was granted by the Tehran University of Medical Sciences Ethics Committee (IR.TUMS.IKHC.REC.1403.292). The study population comprised liver and kidney transplant recipients (3 to 18 months post-transplant), selected through convenience sampling. Verbal informed consent was obtained after reading a standardized script that explained the study’s objectives, voluntary participation, assurances of confidentiality, and participants’ rights to withdraw at any time. To ensure comprehension, participants were asked to summarize key points of the explanation. All data were anonymized and coded to safeguard participants’ privacy. The researchers ensured that data would be used exclusively for research purposes, and individuals were referred to specialists if any psychological or clinical concerns arose. The study maintained the core ethical principles of respect for autonomy, beneficence, non-maleficence, and justice. For future studies, it is recommended to document consent via audio recording if permitted by ethics approval.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.