Factors associated to depression in renal transplant recipients in Panama.

AIM: High rates of affective disorders have been reported in kidney transplant recipients treated for end-stage renal disease. Latin America has experienced a significant increase in transplant activity in recent decades, but there is a dearth of data regarding psychosocial issues following kidney transplantation. The aim of this study was to measure the prevalence of depression and the demographic factors associated to depression among renal transplant recipients in Panama.
MATERIALS AND METHODS: This cross-sectional study was conducted between March to May 2010 in a hospital setting during routine outpatient evaluations. The study included 119 renal transplant recipients (58 males, 61 females). Depressive symptoms were measured using the self-report Hospital Anxiety and Depression Scale and diagnoses were established by a trained psychiatrist using the Mini-International Neuropsychiatric Interview. Regression models were used to explore the association between depression and sociodemographic variables.
RESULTS: The prevalence of depression was 11.8% among transplant recipients. Linear regression indicated that the presence of an anxiety disorder, increasing age, and lower education levels were significantly and independently associated with depressive symptoms. Logistic regression analysis confirmed that anxiety and a perception of negative social support significantly increased the likelihood of depression.
CONCLUSIONS: These findings have important clinical implications. Depression after kidney transplantation has been shown to affect health outcomes adversely. Our results underscore the need to assess depressive symptoms as well as other affective disorders as part of the screening and treatment of renal transplant patients in Panama.

INTRODUCTION

It is well-established that kidney transplantation promotes survival in patients with end-stage renal disease (ESRD).[12] However, the success of transplantation surgery is not ensured, and transplant recipients also experience a significant amount of psychological distress[3] and are at risk for developing depression.[4] Depression has been shown to negatively impact patient outcomes, including graft and patient survival.[35] Moreover, depressive symptoms in transplant recipients increase the risk of noncompliance to treatment regimens, leading to poorer health outcomes.[67]

Studies examining the prevalence of depression in renal transplant subjects have yielded estimates of 22-41%.[489] The literature suggests that renal transplantation recipients are at risk of developing particular psychiatric disorders during the posttransplantation period, namely, depression, anxiety, and adjustment disorders.[10] These comorbidities may contribute to unfavorable outcomes and a higher risk of mortality,[35] particularly in recipients with poor compliance to treatment recommendations.[7] Despite the rates of depression following transplantations, transplant guidelines do not include considerations about the screening, evaluation, or treatment of psychiatric comorbidities in posttransplant patients.[11] Moreover, although some studies have reported the prevalence and impact of affective disorders among kidney transplant recipients in various geographical regions, there is a dearth of data from Latin America, a region that has experienced a significant increase in transplant activity in the past decade.[12] The identification of risk factors associated with depression in transplant recipients in this region will enable the development of appropriate protocols for screening transplant candidates and improving patient outcomes.

Previous studies of kidney transplant recipients have identified various risk factors associated with the presence of depression. Depression increases the risk of treatment noncompliance,[713] and the association is of particular importance due to the potentially adverse effects of noncompliance on health outcomes.[6] Other risk factors for depression after transplantation include gender,[1415] living alone,[9] number of comorbid conditions,[4] marital status,[34] and type of immunosuppressive therapy.[415]

The aim of this study was to describe the prevalence of depression and identify predictors of depression among kidney transplant recipients in Panama.

MATERIALS AND METHODS

Participants

This cross-sectional study was conducted between March and May 2010. A total of 119 renal transplant recipients (58 males, 61 females) were recruited at the Complejo Hospitalario Dr. A. A. M. Hospital in Panama during routine outpatient evaluations. Inclusion criteria were having received a kidney transplant at the Dr. A. A. M. Hospital, having attended the outpatient services for a scheduled follow-up visit and being medically stable (not hospitalized). Exclusion criteria were being younger than 18 years of age and being hospitalized. We collected information about age, gender, level of education, marital status, employment status, perceived social support, duration of dialysis treatment prior to transplant surgery, posttransplant period, treatment adherence, and number of comorbid diseases through self-assessment questionnaires. Depression was assessed through self-report measures and by psychiatric interviews. The study was approved by the institutional ethics committee, and all participants provided signed written informed consent prior to their inclusion in the study in accordance with the 2000 Declaration of Helsinki.

Depression and anxiety assessment

Depressive symptoms were assessed using the Spanish version of the Hospital Anxiety and Depression Scale (HADS),[16] a self-report rating scale validated for use in Spanish-speaking populations.[17] The HADS has been shown to be a reliable and valid instrument for identifying psychiatric cases of anxiety and depression, and assess symptom severity, in ambulatory medically ill patients.[1819] The instrument has favorable sensitivity and specificity for detecting and discriminating among psychiatric disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).[20] The HADS contains 14 items and 2 subscales (anxiety and depression). Each item describes a depression or anxiety state, and the subject is instructed to assess symptoms over the preceding week. Each item is scored from 0 to 3 on a Likert scale (0=as much as I always do; 1=not quite so much; 2=definitely not so much; 3=not at all), giving a maximum score of 21 on each subscale. Following the guidelines regarding optimal cut-offs for the Spanish version of the HADS,[17] scores of ≥5 on the depression subscale were considered a case of possible psychological morbidity.

An experienced psychiatrist conducted the Mini-International Neuropsychiatric Interview (MINI)[21] to establish specific psychiatric diagnoses. The MINI is a short, structured diagnostic interview validated to guide the diagnosis of the principal psychiatric disorders of axis I DSM-IV[20] and the International Classification of Diseases (ICD-10).[22] The administration time is approximately 30 min and the interview content reliably elicits symptom criteria used in making DSM-IV and ICD-10 diagnoses.[21] Agreement between MINI diagnoses generated by general practitioners and expert psychiatrist diagnoses has been shown to be acceptable at the level of primary health care for the most prevalent disorders, including depression and generalized anxiety disorder.[23]

Statistical analysis

Statistical analysis was carried out using SPSS 19.0 software (SPSS, Chicago, IL, USA). Continuous variables were analyzed using analysis of variance (ANOVA), and categorical variables were analyzed using Chi-square (X2) test. Bivariate analysis was performed using Pearson correlation analysis. Evaluation of linearity led to the log transformation of the HADS depression score, which was used in ANOVA and linear regression analyses. Linear regression was conducted to analyze factors independently predicting the severity of depressive symptoms. Logistic regression using the diagnosis of depression as the dependent variable (based on the MINI) was used to assess the influence of variables on the presence of clinical depression. Variables that showed a significant association with depressive symptoms in bivariate analysis (Pearson correlation analysis), as well as variables associated with depressive symptoms in prior research, were entered into multivariable models. P values less than 0.05 were considered statistically significant.

RESULTS

Demographics

Data for HADS depression score were not available for three kidney transplant recipients due to inappropriate completion of the questionnaire, but all 119 subjects underwent the neuropsychiatric interview. The main characteristics of the study population are shown in Table 1. Sixteen [13.8%; 95% confidence interval (CI): 7.6-19.9%] of the transplant recipients were found to have HADS depression scores equal to or above 5 (our cut-off value); fourteen (11.8%; 95% CI: 6.0-17.6%) of the recipients were diagnosed with clinical depression following the structured interview. The distribution of underlying kidney diseases among transplant recipients was the following: Glomerulonephritis (n=33), diabetic nephropathy (n=7), polycystic kidney disease (n=7), hypertensive nephropathy (n=53), and other or unknown kidney disease (n=19).

Table 1

Kidney transplant recipients’ sociodemographic characteristics

Associations of depression with demographic variables

Age was significantly correlated with the HADS depression score [Pearson r=0.26, P=0.005], but no correlation was found between posttransplant period and depression score. There was no association between depression and gender, marital status, duration of dialysis treatment or number of comorbid conditions. Level of education was significantly associated with the HADS depression score (P=0.025), with university educated recipients reporting significantly less depressive symptoms than recipients who completed secondary school but did not attend university, although no association was found between level of education and depression diagnosis. Those who perceived poor social support reported more depressive symptoms than those whose perception of social support was positive (P=0.040), and a significantly greater prevalence of depression was found in recipients with a negative perception of social support (37.5%) relative to those with a positive perception (7.4%), P=0.006. Recipients who reported compliance to treatment regimens reported also significantly less depressive symptoms than recipients who reported noncompliance (P=0.025), although no differences were found with respect to the diagnosis of depression. Last, employed recipients reported significantly less depressive symptoms than unemployed recipients (P=0.008), but no differences were found with respect to the diagnosis of depression.

Multivariable analyses for variables predicting depression

A hierarchical regression analysis was conducted to determine the best predictors of depression symptoms as assessed by the HADS depression score [Table 2]. At the first step, age and level of education were entered into the equation. These variables explained only 9.6% of the total variance, and each made a significant contribution to the prediction of depression severity (P≤0.01 for each variable). After controlling for the variance accounted for by these variables, perceived social support, treatment compliance, and employment status were entered into a second step through the stepwise method. The presence of an anxiety disorder was also included in this step based on research indicating that depressive and anxiety disorders commonly occur together in individuals with chronic illness.[24] The total variance explained increased to 25.4%, but only the presence of an anxiety disorder significantly predicted depressive symptoms in participants (P<0.001).

Table 2

Regression analysis of predictors of depressive symptoms* in kidney transplant recipients

Forward logistic regression was conducted to determine the independent association between the sociodemographic and clinical variables and the presence of depression as assessed by the neuropsychiatric interview. A diagnosis of depression was the dependent variable. The same variables included in the linear regression model were included in the logistic regression model through the stepwise method. Results indicate that perceived social support and the presence of an anxiety disorder were independently and significantly associated with the presence of depression (P<0.001). The model correctly classified 94.5% of the cases. Adjusted odds ratios for perceived social support indicate substantial change in the likelihood of depression, namely, among transplant recipients who perceived poor social support, the odds of being depressed were 12.6 times greater than those whose perception of social support was positive (95% CI: 1.3-122.8, P=0.029). The presence of an anxiety disorder was also a significant predictor of depression, with those suffering from an anxiety disorder being significantly more likely to also suffer depression (adjusted odds ratio: 0.03; 95% CI: 0.004-0.323, P<0.01).

DISCUSSION

The results of this study suggest that anxiety significantly predicts severity of depression and also increases likelihood of the same in transplant recipients. Moreover, we found that a perception of poor social support was associated with an increase in the likelihood of depression, a finding that is consistent with previous reports that indicate that factors related to social support, namely a less supportive family environment, living alone and lower marital satisfaction, are strongly associated with an increased likelihood of depression in renal transplant and ESRD patients.[492526] We did not find any statistical association between depression and gender, marital status, number of comorbid diseases, time elapsed since renal transplantation, or primary cause of kidney disease. Studies of kidney transplant recipients have observed associations between depression and various factors, including graft failure,[15] being female,[1415] poor treatment compliance,[713] living alone,[9] not having a regular income,[9] being single,[34] and disease comorbidity.[4] Larger sample sizes with better statistical power may be necessary to detect such differences.

Based on reports that suggest that comorbid anxiety and depression are prevalent in renal transplant recipients,[3510] we measured the association between anxiety and depression. The prevalence of anxiety was 15.1% among transplant recipients. We found a positive association between anxiety and depressive symptoms in linear regression, and likewise, a significant effect of anxiety on the likelihood of depression. Depressive and anxiety disorders are closely linked, both in their triggers, symptoms and pathophysiology. High rates of comorbid anxiety and depression have been reported for ESRD patients[2728] and transplant recipients,[810] and may increase the risk for negative health outcomes.[15] In this regard, applying a brief self-report scale following kidney transplantation may be a powerful and simple way to detect depressive symptoms and potentially influence health outcomes among recipients.

It has been reported that the prevalence of depression in ESRD patients decreases after renal transplantation,[34] but prevalence estimates among transplant recipients are still higher than in the general population, ranging from 22% to 41%.[489] The present study found a relatively low prevalence of 13.8% using a self-report scale of depressive symptoms and 11.8% using a structured neuropsychiatric interview at a median posttransplant period of 4.8 years. International reports of prevalence vary widely from one trial to another. In Japan, a prevalence of depression of 41.4% was reported using the Zung Self-Rating Depression Scale in transplant recipients measured at an average of 10 years posttransplant.[9] In Turkey, comparisons of depression rates before and after renal transplantation yielded estimates of 7.4%, 14.8%, 77.8% for severe, mild, and nondepressed patients, respectively, using the Beck Depression Inventory at an average of 3 years posttransplant.[3] In a retrospective analysis of insurance claims made in the US, a cumulative incidence of 9% was found at 3 years posttransplant.[15] Discrepancies between ours and previous reports of depression prevalence among renal transplant recipients are probably due to differences in diagnostic and inclusion criteria and methods of assessment among studied samples. For example, studies of depression in ESRD patients suggest that multiple assessments of depression may be necessary to more accurately predict the effects of depression on health outcomes,[29] and the same may be true when assessing depression prevalence following renal transplantation. Culture may also play an important role in how depressive symptoms are perceived and reported,[30] an issue that merits further study in our population.

The strength of the present study was the use of both self-report measures and structured clinical interviews to assess depression in our population. We employed the HADS depression scale, a self-report measure, to identify and assess severity of depressive symptoms. The HADS has been widely employed to evaluate the presence and severity of depression in clinical and research settings, and it is especially useful for detecting major depression.[1819] We also applied DSM- and ICD-based criteria[21] to corroborate the self-reported HADS findings. The HADS identified 16 patients with clinical symptoms of depression, while the structured interview revealed that 14 of these cases met the criteria for clinical depression. The discrepancy can be explained because the HADS is a screening instrument with high sensitivity whose purpose is to identify as many depressed patients as possible, whereas the MINI is a diagnostic instrument and is intended to maximize the proportion of nondepressed patients who score negative (specificity) and the proportion of positive test results corresponding to a diagnosis of depression (sensitivity). Importantly, our results underscore the utility of screening instruments for detecting depression in transplant recipients. Our finding that 11.8% of transplant recipients had diagnosable depression several years into the posttransplant period should alert health care providers of referring kidney transplant recipients for psychiatric consultation, particularly in aged individuals who lack social support.

This study has some limitations. First, the cross-sectional design prevents us from inferring causality from the associations that were found between sociodemographic variables and depression. Based on published reports, depression could be a consequence of intermediate factors related to poor health, such as loss of occupational status, physical function, and general cognitive capacity, all of which have been linked also to anxiety.[3132] Second, self-ratings on sociodemographic items may have been influenced by response bias. Additionally, potentially relevant recipient- and donor-related factors were not included in the study. The R square model fitting (25.4%) in linear regression implied that other factors influencing depression were not included in the model. Last, the small number of depressed patients in our study may have limited our ability to detect statistical associations between depression and sociodemographic variables in this sample. Nonetheless, the findings are notable because the present study represents the first report in Panama of depression prevalence and associated factors in the renal transplant population using validated psychometric instruments. The findings are timely due to a growing awareness of the effects of depression on patient health outcomes and a lack of regional data addressing these issues in transplant recipients.

Depression is a complex medical condition affected by multiple factors (biological, psychological, and social) and whose consequences include a decreased quality of life, increased burden on health services, increased risk for comorbid medical conditions, decreased productivity, among many others. Likewise, the variables associated to depression among kidney transplant recipients are multiple and often interrelated, and are increasingly being recognized as important to health outcomes across all forms of chronic illness.[33] Renal transplant recipients generally experience a long period of adaptation prior to transplant surgery, as patients struggle to cope with chronic illness. The transplant process, despite improving patient health and daily function, also causes severe emotional distress.[3456] In this study, a perception of poor social support and the presence of anxiety disorder were associated with greater depression in the posttransplant period. Therefore, in addition to physical health parameters, assessments of depression and other affective disorders during routine evaluations of renal transplant recipients are warranted. The real challenge is to develop successful interventions to treat depressive symptoms and improve health outcomes after kidney transplantation.