Kidney disease is one of the most striking examples of health disparities in American public health. Disparities in the prevalence and progression of kidney disease are generally thought to be a function of group differences in the prevalence of kidney disease risk factors such as diabetes, hypertension, and obesity. However, the presence of these comorbidities does not completely explain the elevated rate of progression from chronic kidney disease (CKD) to end-stage renal disease among high-risk populations such as African Americans. We believe that the social environment is an important element in the pathway from CKD risk factors to CKD and end-stage renal disease. This review of the literature draws heavily from social science and social epidemiology to present a conceptual frame specifying how social, economic, and psychosocial factors interact to affect the risks for and the progression of kidney disease.
- psychosocial factors
- socioeconomic factors
- environmental factors
- end-stage renal disease
- chronic kidney disease
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- psychosocial factors
- socioeconomic factors
- environmental factors
- end-stage renal disease
- chronic kidney disease
Recent estimates indicate that more than 26 million people in the United States have some form of chronic kidney disease (CKD) and are at risk for kidney failure or other complications.1The number of individuals requiring dialysis treatment or a kidney transplant has more than doubled2during the period from 1991 (209,000) to 2004 (472,000). Morbidity and mortality concerns are exacerbated by the financial burden associated with treating kidney failure or end-stage renal disease (ESRD); the annual cost of treatment approaches $70,000 for each patient.3Projected Medicare expenditures associated with caring for patients with ESRD4,5will approach $28 billion in 2010. It is noteworthy that these projections do not account for other costs such as lost productivity. The considerable financial and social implications associated with CKD underscore the need for scientists to give substantial attention to this chronic condition.
Kidney disease in the United States is not randomly distributed across the population.6-9For example, the prevalence of ESRD among African Americans is 4 times greater than the corresponding prevalence of their white counterparts.2,10,11African Americans also require dialysis or transplantation at younger ages and have greater incidence rates of ESRD at each decade of life compared with any other racial/ethnic group.4,11
Racial/ethnic disparities in kidney failure can be linked to group differences in the rate of progression from CKD to ESRD.4Accelerated rates of progression have been generally thought to be a function of disproportionately high levels of CKD risk factors (ie, diabetes, hypertension, and obesity). However, the presence of these comorbidities does not adequately explain the elevated rate of progression from CKD to ESRD among high-risk groups such as African Americans or individuals with a low socioeconomic status.9We believe that the social environment is an important yet overlooked element that contributes to the progression of CKD and its complications. The behavioral science literature has established that the environments in which individuals reside and work have consequences for their psychological and physiological well-being.12-14Therefore, we draw heavily from the social science and social epidemiological literature to illustrate how exposure to social environmental stressors (eg, poverty and discrimination) can adversely affect psychological functioning and prompt responses in the nervous and vascular systems that place individuals at a greater risk for CKD progression and complications. Figure 1 depicts a heuristic model of the relationship between social environment and kidney disease.
The concepts introduced in this manuscript outline multiple pathways through which economic and social environmental stressors and psychological factors can have implications for kidney disease and its progression to kidney failure and premature mortality.
SOCIAL ENVIRONMENTAL STRESSORS AND HEALTH
The evolving science of CKD has recognized the important role of a complex web of traditional biomedical risk factors and nontraditional, nonbiomedical risk factors that interact to affect CKD progression and complications.8,9,15,16Social science and social epidemiologic research has established that social environments have important consequences for the well-being of individuals.17-20The economic and social standing of communities and families often provides access to important social, emotional, and material resources that help individuals care for themselves and others. Race, sex, and socioeconomic status have important implications for individuals, families, and communities because they can play a critical role in the formation and navigation of difficult social and economic environments where opportunities for upward mobility are scarce. Three important components of the distressing or unhealthy social environments are (a) poor residential conditions, (b) economic deprivation at the household level, and (c) social stressors such as racism or discrimination.8,21-24
The lack of structural changes in the economy for the last 4 decades after the civil rights movement has continued the intense level of residential segregation and has left many African Americans and the poor unable to move out of areas plagued by substandard educational resources, inadequate housing, family disruption, general disorder, pollution, and violence.25-28Recent epidemiologic research has shown that living in such conditions have consequences relative to a number of health outcomes such as infant mortality, low birth weight, and general health and well-being.29-31An emerging body of research in the nephrology community has begun to consider the relationship between socioeconomic position and CKD-related outcomes. The findings from this line of research suggest that economic factors at the individual and community levels have implications for kidney disease.8,32-36It has been suggested that the excess risks for chronic diseases such as CKD among groups such as African Americans are a function of economic deprivation. However, racial disparities in the prevalence and progression of kidney disease continue to persist even when controlling for socioeconomic position at the individual and community level.8,35,36The findings from this line of research demonstrate that economic disadvantages are only partially responsible for racial disparities in kidney disease, suggesting that other social environmental factors contribute to CKD and its complications among high-risk populations.
Racial discrimination and institutionalized racism, for example, are stressors associated with the social environment of many African Americans. Even though it has been nearly forty years since the end of the civil rights movement, African Americans continue to have encounters with individuals and institutions that they believe to be racially motivated.22,37-40Repeated exposures to interactions perceived to be discriminatory or racist, such as unfair treatment on the job, in the housing market, or at public events, can elicit a physiological response.41-43Recent studies have shown that bearing the burden of unjust treatment is related to CKD risk factors such as elevated blood pressure,42,44which suggests that being subject to discrimination/racism can adversely affect CKD progression and complications. This line of research provides evidence linking social and economic conditions to health outcomes.
PSYCHOSOCIAL FACTORS: BRIDGING SOCIAL ENVIRONMENT AND HEALTH OUTCOMES
Social scientists have noted that living in economically and socially challenging environments can be psychologically harmful.45-47Constant exposure to distressing environments can reinforce constraints on one's existence and lead to higher levels of anger, anxiety, depression, and/or stress.48-50The number of studies examining the relationship between psychosocial factors and kidney disease has grown in recent years, as a larger segment of the nephrologic community has become interested in identifying and addressing modifiable risk factors.51However, the study of the psychosocial aspect of nephrology is still relatively new and requires scientists to devote considerable attention to nontraditional risk factors such as anxiety, stress, and social support.52We believe that this line of research, referred to as psychonephrology,53may provide unique insights into the development and progression of kidney disease.
Depression is a disorder whereby individuals experience a depressed mood along with other symptoms such as the loss of interest or pleasure in activities, significant weight loss or weight gain, insomnia or hypersomnia, fatigue or low energy, low self-esteem, poor concentration, feelings of hopelessness, guilt or worthlessness, or recurrent thoughts of death.54This mental condition has been associated with chronic illnesses including CKD risk factors such as hypertension and diabetes.55,56The nephrologic community has identified depression as the primary mental health problem in patients with ESRD. As such, it has received the bulk of attention from scientists who attempt to understand the relationship between psychological functioning and kidney disease. The evidence of the relationship between depression and patients with kidney disease not receiving renal replacement therapy is not conclusive.51,57,58Recent reviews of the psychonephrology literature suggest that inconsistent results are linked to methodological issues including the measurement of depression and study design.55Studies examining the correlation between depression and health outcomes, for example, vary in the extent that they account for other comorbidities such as individual health status and unhealthy behavior.51,55,59,60For example, significant weight loss may not be a sign of depression but an indicator of undiagnosed diabetes or unreported drug use. It is also important to note that most of the research examines depression among patients with ESRD. An implicit assumption undergirding this research is that depression emerges from the ESRD diagnosis, hemodialysis, or renal transplantation. However, it may be the case that depression leads to behaviors (eg, illicit drug use) that contribute to the development of CKD. Additional research work is needed to specify the process through which depression elevates risks for CKD progression and complications.
Anxiety is a state in which individuals are adversely affected by "feelings of being unable to predict, control, or obtain desired outcomes."61Early studies investigating mortality among patients with psychiatric disorders yielded results that demonstrated a positive correlation between panic disorder and mortality.62Subsequent studies that have examined the relationship between anxiety and adverse cardiovascular conditions found that individuals with anxiety disorders had elevated risks for coronary heart disease and sudden cardiac death.59,63,64The risk profiles for cardiac and renal outcomes are similar; however, anxiety disorder has received little attention in the nephrology literature.52As such, research in this area is minimal because scientists have only begun to generate prevalence estimates for anxiety disorder among patients with ESRD. The results from 2 recent studies indicate that the prevalence of anxiety disorder among patients undergoing dialysis range65,66between 27% and 30%. Research in this area is confounded by methodological issues such as the variety of anxiety disorders, the multiple ways anxiety can be measured, and less than optimal study designs.52,60,63,67It is also noteworthy that anxiety is often linked with other mental illnesses such as depression, making it difficult to differentiate the impact of anxiety from other mental conditions.60For example, a study of patients with heart disease revealed that most patients with diagnosis of anxiety symptoms were reacting to the stress of their medical condition and hospitalization.68Additional research is needed to estimate the level of anxiety among individuals with CKD to determine how this disorder impacts the progression of CKD and to help scientists disentangle the impact of anxiety with greater precision to increase the likelihood that appropriate interventions and therapies are used in CKD populations.
Anger and Hostility
Anger and hostility are tightly correlated negative affective dispositions. Anger refers to strong emotions associated with perceived or actual unjust treatment or some other grievance. Hostility connotes an enduring disposition that expresses cynicism, suspicion, and/or resentment. The link between these dispositions and health outcomes was established when psychoanalysts described episodes of anger or hostility among patients with heart disease or hypertension.69,70No studies to date have examined how these factors are correlated with kidney disease. However, research has found anger and hostility to be positively correlated with hypertension, a major risk factor for CKD and its progression to ESRD.59,60,71This line of inquiry can demonstrate how psychonephrology aids in the understanding of the development and progression of CKD among high-risk populations such as African Americans because exposure to discrimination can trigger suspicion or mistrust (hostility) and evoke anger or other negative emotions.72-74However, a number of critical issues associated with measuring anger or hostility needs to be addressed before research along these lines can be pursued.
Stress is a condition whereby environmental factors tax or exceed the adaptive capacity of individuals to a point where psychological and physiological responses may place them at risk for disease.75Selye76observed that long-term exposure to overwhelming environmental conditions could be associated with tissue damage and disease. Subsequent work in this area has demonstrated that stress can also have implications for the development and progression of CKD. A few studies have presented evidence suggesting that stress is directly associated with CKD risk factors such as hypertension.12,77,78It has also been suggested that stress associated with social and/or economic disadvantages has implications for CKD development and progression through correlations with other psychosocial factors and comorbid behaviors such as alcohol, tobacco, and drug use.14,79
Scientists agree that stress can have implications for health outcomes such as kidney disease. However, the relationship between stress and chronic diseases such as CKD has not been pursued extensively. One factor contributing to the paucity of research in this area is that stress is a multidimensional concept that has yet to be definitively and comprehensively operationalized. Stress measures such as the Perceived Stress Scale80are brief indices designed to capture the degree to which situations are appraised as stressful. However, these measures are not comprehensive as they do not consider stress emerging from financial difficulty, neighborhood dynamics, illness, or disease. Future studies must incorporate a multidimensional stress measure to specify the relationship between stress and the development and progression of CKD with greater precision. Additional work is also needed to determine whether the correlation between stress and kidney disease is modified by group (eg, race, sex, and social class) and/or group membership. This line of research could help us gain some understanding relative to the disparities in CKD progression and complications.
Classic social science asserts that social relationships affect an individual's well-being.81It has been well established that patients with sparse social networks and low levels of social support have an increased risk for death.82-84Individuals who live alone or have minimal contact with friends, relatives, or acquaintances have been found to have higher rates of cardiovascular disease morbidity and mortality than persons who are integrated in social networks.85-87
The relationship between social relations and kidney disease has not been pursued extensively. A few studies have examined the relationship between social support and depression, quality of life, compliance, and survival rates among patients undergoing hemodialysis, and they determined that social support is inversely related to morbidity and mortality risk.88-91These studies provide evidence that positive social support can be a protective factor for individuals dealing with time-consuming, long-term therapy associated with ESRD.82
The existing literature suggests that involvement in dense social networks and emotionally supportive relationships can be a protective factor against environmental threats to psychological and physiological health.92,93However, the impact of social support has been assessed primarily in patient populations. Research has not determined the degree to which social support has implications for the development and progression of CKD. It is not clear how social support interacts with environmental factors or other psychosocial factors to affect the health of individuals at risk for CKD or who are in the early stages of CKD. This suggests that future studies should examine the relationship between social support and the development and progression of CKD while also considering social and psychological challenges that at-risk individuals (eg, racial/ethnic minorities and the poor) confront on a regular basis.
The mechanisms by which social environment and psychological factors affect health are unknown. No study to date has developed a comprehensive biopsychosocial model outlining the biological pathways between these factors and the development and progression of CKD. Developing and testing biopsychosocial models have proven to be difficult because exposures to many of the social, environmental, and psychological factors cannot be recreated in a laboratory setting.94However, studies examining the relationship between acute stress and pathophysiology highlight some of the biological processes associated with CKD risk factors and the progression of CKD.
Many studies have examined the effects of acute stress on blood pressure, heart rate, and vascular reactivity.95-98In general, both blood pressure and heart rate increase, and vascular reactivity decreases with most models of acute stress. The extent to which the cardiovascular responses occur and recover depends on ethnicity, socioeconomic status, and sex, with African American males being affected the most.99-101This response is thought to be associated with alterations in the sympathetic/autonomic nervous system activity, the hypothalamic-pituitary-adrenal axis, inflammatory cytokines, and endothelin-A.102,103These alterations, especially in the sympathetic nervous system activity, may be more debilitating in African Americans and provide a hypothesis to link increased life stressors with the higher rates of hypertension seen in that population.104,105A pathologic link between stress, hypertension, and CKD is possible, as renal sympathetic nerves innervate all segments of the kidney, and neural mechanisms regulate sodium and water retention.106
Mental stressors can contribute to CKD via other mechanisms. Diabetes is currently the leading cause of ESRD,7and type 2 diabetes mellitus is associated with insulin resistance. Environmental stressors contribute to the development of insulin resistance, metabolic syndrome, obesity, and ultimately diabetes.107-109The biologic link is thought to involve alterations in the neuroendocrine system including the hypothalamic-pituitary-adrenal axis (increased glucocorticoid and other stress hormones) in addition to sympathetic nervous system factors and inflammatory cytokines.97,110
Stress is also thought to have implications in utero. The Barker hypothesis posits that disruption of the fetal environment or undernutrition translates into pathology.111Cell division and subsequent fetal growth are clearly influenced by products of the hypothalamic-pituitary-adrenal axis and neuroendocrine hormones. Undernutrition brought about by stress can slow cell division in a manner that adversely impacts the number of cells in particular organs, and ultimately, fetal growth. These and other alterations in the fetal environment are thought to contribute to low birth weight, a factor that has been associated with CKD, metabolic syndrome, and diabetes in adult life.112
Recent studies have also examined the extent to which genes are associated with CKD and ESRD in at-risk groups.113-115This line of research has yet to identify specific genes associated with kidney disease in African Americans; however, MYH9 has emerged as a promising candidate.114This gene has been found to be an important factor associated with the progression of nondiabetic ESRD. However, further research is required to specify the degree to which MYH9 and other genes account for the excess risk of kidney disease for groups such as African Americans.
In summary, repeated mental stressors appear to enhance sympathetic nervous system activity, increase glucocorticoid secretion, and potentially increase levels of inflammatory cytokines. These factors contribute to higher prevalence of hypertension, diabetes, and vascular disease, all major risk factors for CKD. The physiologic effects may be experienced in utero, exerting early influences that may further heighten the adult risk for CKD. In patients with CKD, the levels of another hormone, renalase, that metabolizes products of the sympathetic nervous system, are lower.116,117Therefore, it is plausible that the long-term psychological stressors result in unchecked increased sympathetic nervous system activity once CKD develops, which sets in motion a vicious cycle.
POTENTIAL AVENUES OF INQUIRY AND CONCLUSIONS
For the last 2 decades, there has been an increase in attention being given to nonbiomedical mechanisms that affect health outcomes. This paper contributes to this effort by drawing from social science and social epidemiological literature to present a conceptual framework that specifies how social, economic, and psychosocial factors affect the risk for CKD development and progression. The ideas presented here highlight some provocative avenues for future research. Methodological development, however, is one area in need of considerable attention. Many of the factors discussed in this paper are measured with indices that do not adequately capture important dimensions of socioeconomic environments or psychological functioning. Development and refinement of environmental and psychosocial factor measurement are critical for the development of testable biopsychosocial models that specify the process through which environmental conditions get under the skin. The prospects for addressing this challenge are brighter with the emergence of the Jackson Heart Study. The JHS is the largest population-based study of African Americans that collects information including the traditional biomedical risk factors that are associated with CKD in addition to nontraditional risk factors such as economic resources, racism/discrimination, anger, anxiety, depression, stress, and social support. The wealth of data collected by JHS makes it uniquely suited for studies examining how socioeconomic environment and psychosocial factors are associated with CKD and other cardiometabolic outcomes among African Americans. This study can be a vehicle through which psychonephrology extends into the general nephrologic community.
Biopsychosocial model development also has implications for the effort to understand and address racial/ethnic variations in renal outcomes. African Americans have a diagnosis of CKD earlier in life and progress to ESRD at a faster rate than whites. Yet, studies have found that African Americans undergoing long-term dialysis have better survival rates than their white counterparts.118A number of explanations have been posited to reconcile these paradoxical findings including survival bias119and greater access to health care via Medicare coverage.9Biopsychosocial models can introduce and investigate other factors such as resiliency or social networks. Serious chronic conditions such as ESRD can impel individuals to draw upon resources marginalized groups such as African Americans are thought to use during difficult periods.
Research using biopsychosocial frameworks can give greater attention to the complexities associated with the environments in which individuals are embedded. The empirical models emerging from this line of work will need to account for environmental differences and the psychological toll that result. Rigorous assessment of biopsychosocial models may require scientists to use different statistical methodology. Factors such as racism, poverty, depression, anxiety, and anger can interact to assault the health of individuals. As such, it may be necessary to use methods such as structural equation modeling that enable scientists to observe group differences in how socioeconomic distress and mental well-being are simultaneously related to the development and progression of CKD.
It is also noteworthy that results from this line of work can have implications for clinical- or policy-oriented segments of the nephrologic community. Identifying group-specific processes associated with kidney disease would enable not only health care providers but also public health officials to develop culture- and context-specific interventions to help reduce disparities in CKD development and progression in the short term and eliminate them in the long term.
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