An Integrative Review of Depression in Patients Receiving Hemodialysis for End-stage Renal Disease and the Relevance to Patients With Wounds

End-stage renal disease (ESRD) often is treated with hemodialysis, which carries significant psychological impact along with risks for wound development. Depression is a constant concern. Purpose: An integrative review was conducted to examine studies regarding depression in adults receiving hemodialysis for ESRD. Methods: PubMed and the Cumulative Index for Nursing and Allied Health Literature were searched for English-language publications from 2012 to 2017 regarding ESRD using the search terms epidemiology, hemodialysis, and depression and hemodialysis, depression, nocturnal, and wounds, respectively. Results: Eight (8) of 152 articles found met the inclusion criteria and were categorized thematically. Depression was noted to affect 9.3% to 83% of persons receiving hemodialysis for ESRD. The occurrence of depression does not change across the course of ESRD. Although no publications on patients that included all search terms were found, ESRD and hemodialysis were noted to be independent risk factors for ulcer development, poor healing, and amputation. Wounds can be another source for risk of depression. Conclusion: Although the literature does not include studies that contain all components, ESRD, depression, and wounds are linked. Depression is a common occurrence in patients with ESRD and dialysis. Examining the effect of wounds on depression for these patients is critical. As such, additional research is warranted to explore the interconnections of ESRD, depression, and wounds to improve clinician awareness and patient outcomes.

End-stage renal disease (ESRD) affects approximately 678 383 adults in the United States, with an incidence of 120 688 adults per year.¹ The most advanced form of ESRD occurs when the kidneys fail to meet the body’s needs for filtration of waste and electrolyte and fluid balance. Without these functions, an individual requires an intervention, such as dialysis, to maintain life. Maintenance (sometimes referred to as conventional) hemodialysis is used by 63.1% of individuals receiving treatment for ESRD.¹ 

Retrospective and cross-sectional reviews^2,3 have shown kidney failure and dialysis exert a significant psychological impact on patients; depression is a constant concern. Depression is the common term for persistent depressive disorder or dysthymia. Depression is hallmarked by relentless feelings of sadness or irritability for a greater number of days than not, for a minimum of 24 months, and in the company of increased or decreased appetite, over- or undersleeping, decreased energy, decreased self-esteem, difficulty concentrating, and feeling hopeless.⁴ Depression can occur as the result of a medical condition when: 1) an individual has decreased attention or enjoyment in activities or depressive mood during the course of illness; 2) there is a clinical diagnosis that can account for the psychological disruption by history or clinical testing; 3) the depression is not otherwise well explained; 4) concurrent delirium has not occurred; and 5) when depression is associated with notable distress in the clinical course of a disease or markedly decreased social and occupational participation.⁴ 

ESRD and dialysis can have a significant psychological impact on the person. A major psychological effect is depression. Depression can influence patient care. In addition, patients with ESRD and dialysis are at risk for wound development and complications.^5,6 The purpose of study was to conduct an integrative review about depression in adults receiving hemodialysis for ESRD.

Inclusion/exclusion criteria. An integrative review of PubMed and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) was conducted of peer-reviewed, English-language publications from 2012 to 2017. Search terms used for PubMed included epidemiology AND hemodialysis AND depression. Search terms for CINAHL Complete included hemodialysis AND depression AND nocturnal. Inclusion criteria stipulated the research must include adults >18 years of age who were receiving nocturnal or intensive hemodialysis and had chronic kidney disease (CKD), prevalence data, incidence data, and reports of depression in this population. Research concerning pediatric patients (age <18 years); non-ESRD (eg, acute) cases; nonhuman or animal subjects; patients with glaucoma, mortality risk, left ventricular mass, pruritus (itching), fluid adherence, cardiovascular disease, transplant, and antidiabetic fibromyalgia; and nonhemodialysis patients was excluded. 

A literature search for wounds and ESRD was done separately in PubMed with end-stage renal disease AND wound AND depression for publications from the last 5 years. Two (2) articles were found but neither was appropriate to the review. Another search was conducted with end-stage renal disease AND wound AND dialysis AND research AND last 5 years AND English. Of the 20 publications found, 8 were reviewed.

Data extraction and synthesis. The authors extracted the following information from each included article: study design, sample size, methods, outcomes, prevalence of depression, and conclusions. Findings across all studies were examined to determine prevalence of depression in ESRD for patients on hemodialysis and the current state of the research about how depression effects patients with ESRD.

Searches of the 2 indices revealed 152 articles; 145 were excluded based on the title/abstract. One additional article was found using intensive hemodialysis AND depression in PubMed and included in this study; 3 articles published within the last 5 years were excluded because the primary purpose did not include depression. Ultimately, this review included 8 research articles. None of the studies included patients who had wounds.

Prevalence of depression in adults with ESRD and hemodialysis. Recent research about the occurrence of depression in persons on hemodialysis includes the cross-sectional study by Silva Junior et al,⁷ who investigated the rates of depression among patients (N = 148) who were treated for ESRD using hemodialysis for a mean of 5.3 years in Brazil. Using the Beck Depression Inventory II⁸ as the diagnostic tool, depression was noted in 68% of patients. Mild (49.5%) and moderate (41.5%) depression were the most common forms; 9% of patients were severely depressed and only 15.5% of these were previously diagnosed. For most, depression commenced after starting maintenance hemodialysis, underscoring the correlation between maintenance hemodialysis and depression. Many (54.5%) patients were treated using antidepressants or benzodiazepines. Antidepressants were effective in reducing depression symptomology in >80%. The authors concluded depression often is missed in this population; routine screening for depression and its treatment in patients receiving chronic dialysis is important. 

In their cross-sectional, correlational study, Khalil and Abed⁹ examined whether perceived social support mediated depressive symptoms/quality of life for Jordanian patients (N = 190) with ESRD. Using the Brief Symptom Inventory Depression Subscale and Quality of Life Index,¹⁰ 83% of the surveyed patients had depressive symptoms. Depression was significantly associated with decreased quality of life. Depression is a stigma in the Jordanian culture, reflecting the importance of culture when diagnosing depression. The authors noted the importance of using a standardized method for depression screening. All practitioners need to be involved in the diagnosis of depression.  

Using a cross-sectional design, Santos et al¹¹ investigated the occurrence of depression, quality of life, and religious coping in 161 Brazilian adults undergoing maintenance hemodialysis. Diagnostic/assessment instruments used included the Center for Epidemiologic Studies Depression Scale,¹² Medical Outcomes Study 36-item Short Form Survey,¹³ and the Religious Coping Questionnaire.¹⁴ The prevalence of depression was 27.3%. Seeking religious direction and counsel from God were the spiritual/religious coping methods that were associated with lower depression and higher quality of life. Patients who used negative religious coping, such as blaming God for their illness, were more likely to be depressed. The authors encouraged practitioners to assess their patients’ religious/spiritual beliefs as affecting coping and to provide religious/spiritual resources as needed.

Ng et al¹⁵ longitudinally measured how depression and anxiety fluctuated over 12 months for patients (N = 159) with ESRD on hemodialysis in Singapore. Using the Hospital Anxiety and Depression Scale and the Kidney Disease QoL-Short Form^16,17 to measure depression and quality of participant’s social interactions, depression was found to be present in >50% of included participants. Depression, whether apparent at baseline or as new onset, remained unchanged throughout the 12-month course of the study. Participants had lower perceptions of social connections; these lower perceptions increased their risk of depression and anxiety.

In their cross-sectional design study, Rajan and Subramanian³ explored activity performance (eg, exercise) and how it is influenced by depression and anxiety in Indian patients (N = 50) with ESRD and hemodialysis. The authors used the Beck Depression Inventory II and Beck Anxiety Inventory scales to measure depression and anxiety.^18,19 Performance was measured using the Karnofsky Performance Status Scale, even though this scale is more commonly used with cancer patients.²⁰ The authors reported a strong concordance (.40) between depression and anxiety and their influence on decreased performance status (-.65 and -.64, respectively). Furthermore, the authors suggested physical activity is a viable intervention for improving quality of life for patients with ESRD.

In their retrospective review of ~5 million hospitalized adults with ESRD on hemodialysis from 2005 to 2013, Chan et al² examined gaps in knowledge surrounding depression in hospitalized ESRD patients in the United States. In the 2-group comparison — one group with and the other without depression — depression was a concurrent diagnosis for 9.3% of individuals across the years 2005–2013 and increased from 5.01% to 11.78%. Depression was most prevalent among younger, Caucasian women who had more concurrent diagnoses verses patients with fewer additional diagnosis. (ie, the more concurrent diagnoses, the higher the prevalence of depression). The cost of care was similar for patients with depression compared to those without, even though their hospital stays were longer. In addition, the authors found a decline in mortality rates associated with depression, possibly because the sicker the patient, the less likely a diagnosis of depression.²

Yoong et al²¹ pooled data (N = 526) from 2 controlled (1 randomized) studies in Singapore to compare depression and anxiety in patients with ESRD and hemodialysis as well as patients with (59%) and without (31%) diabetes. Depression (49.9%) and anxiety (45.4%) were elevated and did not differ between patients with and without diabetes. Higher depression rates had a stronger relationship to sociocultural variables than to comorbidities. The authors recommended monitoring depression and anxiety in hemodialysis care and to implement appropriate treatment.

In a randomized controlled trial (N = 332) conducted among patients in the US and Canada, Unruh et al²² explored the effects on depression of in-center intensive (short daily and nocturnal) hemodialysis over a 12-month period. Using the Beck Depression Inventory Scale⁸ and RAND 36-item Health Survey²³ to measure depression and physical health, depressive symptoms did not differ between patients having intensive hemodialysis and in-center hemodialysis; however, intensive hemodialysis improved self-reported mental health, energy, and emotional state. Participant attrition due to death and transplant thwarted the ability to investigate the benefits of nocturnal dialysis, although a nonsignificant decrease in depression scores was reported in this group. Even though this study was randomized, disparate sample sizes between the nocturnal group and the short daily or conventional group limited comparing results.

In summary, depression is common in persons receiving hemodialysis for ESRD and ranged from 9.3%² to 83%.⁹ The studies reviewed were international (Brazil, Jordan, Singapore, India, and US)^{2,3,7,9,11,15,21}; most had small sample sizes ranging from 50 to 190. Studies often included other variables such as anxiety, comorbidities, hospitalization, quality of life, well-being, physical performance, and religion.^{2,3,7,9,11,15,21}  No study stated if a patient had a wound. If a wound was present, it is not known how it affected depression. Providers in all clinical settings need to be cognizant of depression in persons receiving hemodialysis.

Wounds in ESRD patients receiving dialysis. Individuals with ESRD receiving hemodialysis are at risk for both surgical and chronic wounds. Otte et al²⁴ retrospectively examined the risk of ulcers in persons with ESRD and hemodialysis treatment in the Netherlands. The analysis compared 3 groups: patients with CKD Stage 3 with an estimated glomerular filtration rate (eGFR) between 59 and 30 without dialysis treatment for >3 months (n = 539); patients with CKD Stage 4-5 with an eGFR <30 without dialysis treatment for >3 months (n = 540); and patients receiving peritoneal or hemodialysis treatment (n = 259). The incidence of foot ulceration was 4 times greater in the CDK Stage 4-5 group and 8-fold greater in the dialysis treatment group versus the CDK Stage 3 group. These increases occurred even after controlling for risk factors such as diabetes. These patients had high rates of amputation and mortality,²⁴ data that were supported by other retrospective research.²⁵ The authors concluded that maximum effort is needed in foot care and preventive practices for patients with CDK Stage 4-5 and dialysis. 

Orimoto et al²⁵ retrospectively examined the prognosis of Japanese patients (N = 234) who had hemodialysis and a foot ulcer; 84% had diabetes. Surgery included arterial reconstruction (88 limbs) and amputation (119 limbs). Overall, the 5-year limb salvage rate was 53.8%. Risk of death increased with ischemic changes on an electrocardiogram and age on admission. The 5-year survival rate of patients on hemodialysis with foot lesions was 23%, which was worse than lung (29%), stomach (64%), or breast (88%) cancer, to name a few; it was only better than pancreatic cancer (6%). The authors concluded patients with foot lesions receiving hemodialysis have a poor prognosis.

Meloni et al²⁶ retrospectively examined people with diabetes receiving (n = 99) and not receiving (n = 500) hemodialysis in Italy. Dialysis was a negative predictor of healing (dialysis, 30.3% vs not on hemodialysis, 52.6% healed) and positively associated with amputation (14.4% vs 10.8%) and death (21.1% vs 11%). The authors concluded adults on hemodialysis should be considered a special category of patients, such as patients with diabetes, who would need intensive foot care and vascular disease management.

In their prospective, observational design study, Jones et al²⁷ explored the prevalence of risk factors for lower extremity ulcerations in patients (N = 57) receiving hemodialysis and compared these risk factors in patients with (n = 24) and without (n = 33) diabetes in the UK. Risk factors included peripheral neuropathy, peripheral arterial disease, and foot pathology; 2 or more risk factors were found in 28 patients (16 with and 12 patients without diabetes). Only 7 patients (12%) had no risk factors. The initiation of hemodialysis in persons with diabetes was associated with a 3-fold risk of new ulceration in the first year of dialysis treatment. The findings of a descriptive, cross-sectional study by Kaminski et al²⁸ were similar for adults on hemodialysis (N = 450); this sample included persons with diabetes (50.2%,) previous ulceration (21.6%), amputation (10.2%), and current foot ulcers (10%); 50% had neuropathy and/or peripheral arterial disease. Factors associated with ulceration were previous amputation, peripheral arterial disease, and low serum albumin. The authors concluded persons on hemodialysis have a high burden of lower limb complications. 

Wound healing also has been found to be negatively affected by ESRD and hemodialysis. In the comparative study of 2 groups (receiving hemodialysis or not) undergoing endovascular therapy for critical limb ischemia conducted by Honda et al²⁹ among 267 adults in Australia, wound healing rates were significantly lower (79.5% vs 92.4%; P <.001) and time to heal (132 days vs 82 days; P = .005) was significantly longer in patients receiving hemodialysis versus those not on the therapy. Wound recurrence (25% vs 10.2%; P = .007) also was more common in persons undergoing hemodialysis. The authors concluded hemodialysis was an independent predictor of wound healing.

The systematic review and meta-analysis of risk factors for foot ulceration and lower extremity amputation in adults with ESRD receiving hemodialysis by Kaminski et al⁴ found 30 studies and identified the following risk factors: previous foot ulcers, peripheral arterial disease, diabetes, peripheral neuropathy, and coronary artery disease. The authors concluded adults receiving hemodialysis are at higher risk for foot ulceration and amputation. Scholnick³⁰ reviewed the effects of renal disease on wound healing and reported peripheral arterial disease, uremic neuropathy, immunosuppression, dermatologic disorders in renal disease (calciphylaxis), Charcot, and poor self-care negatively affect healing. Maroz and Simman⁵ also published a review that found risk factors for poor wound healing included diabetes, neuropathy, peripheral arterial disease, chronic venous insufficiency, uremic toxins, and aging.

In summary, hemodialysis appears to be an independent risk factor for ulcer development, poor healing, and amputation even when patients do not have diabetes. Also, adults who have a foot ulcer and are on dialysis have a poor prognosis. Although lower extremity amputations have decreased 51% for patients with ESRD from 2000 to 2014, they still occurred at the rate of 2.66 per 100 person-years in 2014.³¹  Patients receiving hemodialysis, regardless of the presence of diabetes, need a concerted and focused effort in preventive foot care practices. 

Wounds and depression. Adults with ESRD and hemodialysis are at high risk for depression; a wound can add to a person’s depression risk. The integrative review found wounds were not discussed in any of the studies reported. Thus, depression associated with wounds was explored in a general manner across varied wound types. In their systematic review of 23 studies on the impact of chronic venous leg ulcers, Green et al³² reported depression was common. In their secondary data analyses, Edwards et al³³ found 2 symptom clusters in patients (N = 318) with chronic venous ulcers²: one noted depression with pain, sleep disturbance, and fatigue. As part of secondary data analyses of outpatients, Bui et al³⁴ examined 561 patients with chronic leg ulcers to identify risk factors associated with infection. Venous ulcers accounted for 388 (74%) of the leg ulcers; depression was 1 of 7 factors independently associated with a leg ulcer infection (odds ratio = 2.78; P <.035). 

In their descriptive study, Souza Nogueira et al³⁵ assessed depression in 30 adults with venous ulcers. Depression was identified in 40% of these patients; it was not significantly related to other sociodemographic variables. The authors concluded depression could occur independent of socioeconomic variables for patients with chronic venous ulcers. 

In a cross-sectional study, Zhou and Jia³⁶ examined depressive symptoms in patients (N = 222) with either venous or nonvenous leg ulcers. Minimal to severe depressive symptoms were present in 81.5% of patients. A positive depression screen was more common in patients suffering from wounds for >90 days’ duration and who had pain. The authors concluded depressive symptoms were common in patients with wounds and recommended clinicians carefully consider a patient’s mental status when caring for a person with leg ulcers. In their prospective, observational study, Walburn et al³⁷ examined the effects of stress, illness perception, and behavior on venous ulcer healing for 63 adults followed for 24 weeks. Controlling for sociodemographic and clinical variables, a slower change in ulcer area was associated with greater stress, depression, and negative perceptions/beliefs about the ulcer, leading the authors to conclude psychological factors should be examined with wound healing.

Udovichenko et al³⁸ assessed depression in outpatients (N = 285) with diabetic foot ulcers as part of a prevalence study on depression and diabetic foot ulcers. Depression was present in 39% of included patients. Fortunately, adults with depression did not have poorer ulcer treatment results. When Ahmad et al³⁹ examined depression and anxiety among Jordanian adults (N = 260) with diabetic foot ulcers, prevalence of depression and anxiety were found to be 39.6% and 37.7%, respectively. Depression was associated with age <50 years old, female gender, currently smoking, foot ulcer present >7 months, and >3 comorbidities than those without depression. The authors did not examine the effect of depression on wound healing. Both studies highlight the importance of psychosocial factors with wounds.

In summary, a high percentage of persons with wounds are depressed. Unfortunately, literature about depression and wounds and ESRD could not be found. The most common wound types where depression was explored were chronic venous ulcers and diabetic foot ulcers. Depression may be a factor of the duration of the wound as well as the psychosocial implications of having a wound such as shame, embarrassment, and loneliness. Thus, having a wound is another reason to assess for depression in persons with ESRD and hemodialysis.

This integrative review of studies about depression in adults receiving hemodialysis for ESRD allowed the authors to apply what was learned about depression to wounds associated with ESRD and dialysis. The goal was to increase awareness of depression as a critical psychological effect when the patient with a wound also has ESRD and is receiving hemodialysis. Depression is a common problem in adults who undergo hemodialysis for ESRD.^2,7,11,15 ESRD and hemodialysis also are associated with the development of wounds regardless of other comorbidities.^4,24-29 Wounds, especially venous and diabetic ulcers, were associated with depression.^32-36,39 ESRD, hemodialysis, wounds, healing, and depression form a set of intersecting factors, but research that links them together is lacking. ESRD, hemodialysis, wounds, and depression are worldwide concerns as shown by the array of internationally focused research on these topics. 

For the wound care clinician, this means assessing patients for depression, especially when ESRD and hemodialysis are present. The causes of depression in patients with wounds are multifold. For patients with ESRD receiving hemodialysis, the presence of a wound can add to depressive symptoms when the wounds are slow healing and painful and the person experiences loss of self-esteem and social isolation.^33,36,37,40 Depression can have marked negative effects on quality of life because the patient becomes less involved in social and occupational activities and may experience lack of social support and meaningful social interactions, shame, embarrassment, and loneliness.^2,11,15,41 Depression can affect adherence to care.³⁰ Some patients may verbalize that they are depressed; others do not recognize it or are worried about a diagnosis of depression for family or cultural reasons. A standardized, validated depression instrument (several are available is recommended to aid diagnosis; these include the Beck Depression Inventory-II and the Center for Epidemiologic Studies Depression Scale, which has several versions, including a version for older adults that has 10 items. Both the Beck Depression Inventory-II and the Center for Epidemiologic Studies Depression Scale have strong reliability and validity and are completed in 10 minutes or less.⁴² The BDI-II has 21 items.⁴² After depression is diagnosed, the patient’s team of clinicians needs to determine the best treatment and follow up in terms of treatment effectiveness.           

Patients with ESRD and hemodialysis should have their feet evaluated on a routine basis, regardless of their diabetes status. Peripheral neuropathy, limited range of motion, foot deformities, and skin and nail pathologies need to be part of the foot examination.^4,27,28,43 Feet should be assessed for pressure markings and wounds from shoes or being confined to bed or chair.²⁸ Shoes should be evaluated for proper fit. Patients may need a referral to a podiatrist for foot care. 

Although many wounds in persons with ESRD and diabetes mellitus occur on the feet, the wound clinician and primary care provider should evaluate the entire body for wounds such as vasculitis and calciphylaxis.³⁰ Uremic pruritus causes itching that may break the skin and result in wounds. Some patients may hide wounds from providers; thus, wounds can become large before these patients seek treatment. Patients should be taught preventive and foot health principles such as foot and skin assessment and the need for routine care by a podiatrist.^4,30 

The presence of peripheral arterial disease should be documented because it is a high-risk factor in ESRD.²⁷ Critical limb ischemia negatively affects wound healing and can increase risk of amputation.²⁵ Patients with ischemia may have pain in the lower extremities and decreased mobility.⁴³ Smoking is related to peripheral arterial disease, and it negatively affects wound healing.³⁹ Patients should be informed of smoking cessation programs. 

Nutrition should be evaluated because malnutrition is common in persons with ESRD.³⁰ Orimoto et al²⁵ noted 2 types of malnutrition: one was related to low protein and energy intake and the other was associated with inflammation. Malnutrition from inflammation was associated with foot ulcers that are difficult to treat because of the need to correct underlying comorbidities. Infection is a concern because renal failure is associated with impaired immune system function.^5,30 

Religion/spirituality and culture may influence the person’s acknowledgment of depression and willingness to receive treatment for it. The patient may respond better with terms such as feeling low or feeling blue than with the term depression. Providing care in a culturally appropriate manner may increase success in terms of wound healing. The quality of interaction these patients have with their health care providers can positively affect mental status, perceived quality of life, and anxiety. Clinicians should foster meaningful interactions, encourage social connectedness, and recognize current coping mechanisms used by their patient to help reduce the high risk of depression patients with ESRD face. 

Implications for research. ESRD, hemodialysis, depression, and wounds are closely linked. Important considerations include, What is the prevalence of depression in patients with ESRD receiving dialysis and who have a wound? For these patients, what is the effect of depression on wound healing? How often should depression be assessed? What is the effect of patient teaching on preventing wounds in persons with ESRD receiving hemodialysis? Research conducted among these individuals may require recruitment across multiple sites to enhance the sample size. Multisite, cross-sectional, or retrospective studies linking ESRD, depression, wounds and wound care are needed.

The purpose of this integrative review was to examine studies regarding depression in adults receiving hemodialysis for ESRD. Kidney failure and hemodialysis inflict a significant impact on patients. The risk of depression in this population has increased 2-fold in less than a decade.2 Assessing patients with ESRD for depression is imperative because it can reduce quality of life. ESRD and hemodialysis are independent risk factors in the development and healing of wounds5,30; having a wound can add to depression. Depression can negatively affect patients’ interest and participation in wound care. The current research identified areas that need improvement in clinical care: assessing depression on a routine basis, cultural sensitivity, social interaction quality, assessing for coping mechanisms such as religion, and supporting mechanisms that improve depression in these patients.9,11,15,21 Implementation of improved care protocols and appropriate assessment of resultant outcomes are warranted.

Ms. Gagnier is a Master of Science in Nursing student, Faculty of Nursing, University of Windsor, Windsor, Ontario, Canada. Dr. Pieper is a Professor/Interim Associate Dean for Faculty Affairs, College of Nursing, Wayne State University, Detroit, MI.

Please address correspondence to: Sheena A. Gagnier, BSN, RN, University of Windsor, Faculty of Nursing, Room 336, Toldo Health Education Centre, 401 Sunset Avenue, Windsor, Ontario, Canada N9B 3P4; email: maloneys@uwindsor.ca.