Pharmacist's Role in Reducing Medication-related Racial Disparities in African American Patients With Chronic Kidney Disease

Abstract Racial/ethnic disparities in chronic kidney disease have been well established. African Americans experience faster progression to end-stage kidney disease and a higher prevalence of kidney-related diseases due to social determinants of health and systemic racism. As the most accessible healthcare professionals, pharmacists have a responsibility to diminish racial health disparities by putting efforts into leading diversity initiatives, committees, task forces, and community outreach events. To effectively engage African American communities, pharmacists must first understand the historical context of distrust in health care, kidney-related health and medication-related disparities experienced by African Americans, and how socioeconomic deprivation impacts the progression of kidney disease. In this article, we review available literature pertaining to these topics and give suggestions on what pharmacists can do to help reduce healthcare disparities in African Americans with kidney disease and to build trust with individuals and their communities to improve their healthcare outcomes. 

KEYWORDS African Americans, chronic, disparities, epigenetics, health disparities, kidney disease, pharmacists, socioeconomic deprivation

CLICK HERE TO GET CISTANCHE FOR CKD TREATMENT

| INTRODUCTION

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), African Americans (AAs) account for 35% of the patients with end-stage kidney disease (ESKD), while making up only 13% of the U.S. population 1 AAs are almost four times as likely to develop ESKD as Whites. Decline in estimated glomerular filtration rate (eGFR) occurs at younger ages and progresses at a faster rate in AAs vs Whites.2 AAs also have a higher prevalence of hypertension3 and develop diabetes at a younger age than Whites.4 Chronic kidney disease (CKD) is often associated with other chronic conditions such as diabetes and hypertension and has been shown to be a risk multiplier for increased cardiovascular mortality. In order to address the racial disparities in kidney disease, efforts must also be made to narrow the racial disparities seen in these other conditions as well. AAs are disadvantaged by social and economic issues that widen health disparities and create challenges relating to health insurance coverage, access to health care, trust in the health care system and results in suboptimal delivery of care.5 Health care professionals must inform themselves about the known racial, ethnic, and socioeconomic. disparities and social inequities in CKD and related diseases in order to adopt strategies to improve health outcomes in vulnerable populations. Since medications are the primary management steps of these related conditions, knowledge of medication-related disparities in AAs living with kidney disease will better arm pharmacists and other healthcare professionals with the knowledge and framework needed to more adequately address medication-related needs in these patients.

The purpose of this article is to highlight the role of the pharmacist in reducing medication-related disparities and provide suggestions that pharmacists can employ to lessen the distrust in the healthcare system that many AAs experience due to discrimination and systemic racism. In the article, we address key drivers of racial health disparities with a focus on kidney diseases, share medication-related experiences of AAs with kidney diseases, and examine factors contributing to medication-related health disparities in these patients.

2 | BACKGROUND 

The Centers for Disease Control and Prevention (CDC) defines health disparities, also referred to as health inequities, as “preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations.” 6 Racial and ethnic disparities exist across all areas of health and are a result of racism in the United States which puts communities of color at a disadvantage and negatively impacts social determinants of health.7 The recent racial reckoning in the United States following George Floyd's murder has intensified the attention toward discussing the role of race, and antiracism specifically, in health disparities research and reporting.8 Importantly, health equity and antiracism instruction and frameworks are being encouraged to be incorporated into the education of pharmacists to more adequately address health disparities.9

Race is a social construct that derives its meaning from social and historical contexts that must be understood as a worldview, not as a physical or biological concept.10 The use of race in the United States dates back to colonial times as a way to distribute power and resources. Racial categories are organized by physical characteristics designed to determine and produce power and do not align with biological genetic variation.11 In effect, the use of race produced social categories that determined the allocation of resources impacting living conditions and ability to achieve health equity. While the reasons remain complex and not clear-cut, those lacking resources such as land, housing, education, access to healthy food and health care suffer worse health outcomes.

Residential segregation is the segregation resulting from policy-level racism that has resulted in poorer living conditions for AAs and other racial groups.12 This has been shown to have adverse health outcomes related to difficulties gaining access to nutritious food, creating barriers to exercise, increasing acute and chronic stress experienced by community members, and limiting access to quality health care and health care information.

Race and socioeconomic status (SES) share a complex relationship but are distinct concepts for understanding health disparities.12 The disadvantage experienced by a racial/ethnic group in regards to access and control over economic, social, and healthcare resources and opportunities is referred to as socioeconomic deprivation (SED) (Figure 1).13 SED relates to discrimination and segregation, poor living conditions, limited access to quality care for the uninsured, poor health literacy, under-funded educational systems, and chronic stress. These factors impact the determinants of CKD such as obesity, hypertension, and diabetes, as well as the progression of CKD to ESKD.13

In addition to understanding the social determinants of health disparities, providers must understand their patients' experiences with the healthcare system and its clinical implications. A national survey including AA and White respondents found that race was strongly associated with physician distrust with AAs having a significantly higher mean distrust index score than White respondents even after controlling for sociodemographic variables.14 The longstanding effects of racism must be recognized in the distrust the AA community holds for the health care system and its providers. Historic inhumane treatment of AAs is widely documented and includes the exploitation of slaves for the advancement of medicine.15 More recently, the Tuskegee Syphilis Study, a 40-year government-run study (1932-1972), deliberately denied treatment to AA men with syphilis in order to document the natural progression of the disease, leaving a powerful legacy of distrust of the medical establishment that persists to this day.

While systemic approaches and policies are imperative for effectively addressing health disparities, how race is understood and approached in clinical care has also been recognized as problematic and suboptimal. How clinicians approach and handle the concept of race has been problematized in research done in primary care settings, relevant to where the majority of kidney disease treatment occurs.,16 Hunt et al. explored how primary care providers perceive and incorporate race into clinical practice.17 The authors found that while there was wide agreement among providers about the importance of race in clinical medicine, how race was defined and the concept applied to individual patients in the clinical setting was inconsistent.17 They concluded that when socioeconomic and lifestyle factors were addressed, providers often relied on presumptions about the racial group rather than developing an individualized approach to evaluating the factors. This reliance on presumptions demonstrates how unconscious biases, or social stereotypes or beliefs about certain groups of people that a person may form outside of their conscious awareness play out in everyday clinical care.18

The role of medications in reflecting and perpetuating health disparities has also been recognized. Hall-Lipsy and Chisholm-Burns examined overall disparities in medication treatment and applied the term “pharmacotherapeutic disparities” to underscore this important and potentially unaddressed contributor to healthcare disparities.19 They found that significant disparities exist across clinical conditions (including the kidney-related diseases of diabetes and cardiovascular disease, CVD), with several examples in AAs. They suggested that several pharmacy-related factors may play a role at the health-system level (eg, disparities in the availability of opioids in communities with fewer white residents), decision-making at the provider level, and attitudes and communication styles at the patient level. Notably, the most common disparity was with receipt of the prescription itself 

FIGURE 1 Socioeconomic deprivation and CKD. Reprinted from Nicholas et al.13 with permission from Elsevier

FIGURE 2 Conceptual model of socioeconomics influencing epigenetic changes. Reprinted from Nicholas et al.13 with permission from Elsevier

which could stem from problems at the system, provider or patient level.19 In 2020, the term “Pharmacoequity” was introduced to underscore the contribution of medication therapy problems to health disparities.20 This draws attention to equity in medication use including access, cost, and quality of care as a means of narrowing disparities in diseases dependent on adherence to medications for optimal disease management. To address medication-related disparities within the context of the lived experience of AAs, it is necessary to identify the medication therapy problems, and then contextualize those problems within the broader racial, social, and economic conditions in which they occur so they can be effectively addressed.

3 | GENETIC POLYMORPHISM AND RACIAL/SOCIAL STRESSES ON EPIGENETICS

SED causes increased psychological, physical, and environmental stress which leads to genetic and neurohormonal changes.13 “Epigenetics” is a term that refers to potentially heritable changes in the genome that can be brought on by environmental events.21 Epigenetics is thought to be the link between AAs and increased CKD risk factor gene expression (Figure 2), including, APOLI variants, and increased oxidative stress to cause an accelerated decline in kidney function and increased cardiovascular complications.21 A study evaluating the effects of APOLI gene variants in AAs found that patients who have two copies of high-risk APOLI variants had a significantly higher risk of developing ESKD compared to those who had none or one copy of the variant.22 Additionally, AAs in the low-risk group (zero or one high-risk variant) had a 40% greater risk of developing ESKD or experiencing a 50% decline in eGFR from baseline compared to Whites. The higher risk that AAs in the low-risk group had for developing ESKD compared to Whites suggests that the racial disparities in CKD progression cannot be fully attributed to genetic factors. Attention is now being focused on the role of epigenetics and health outcomes for AAs.22

It is well known that chronic and acute stress has a negative impact on patients' health, especially related to CVD. However, research is now exploring the degree to which health consequences of racism and discrimination against AAs are passed down transgenerationally through the biological memory of harmful experiences. DNA methylation is thought to be one of the mechanisms of epigenetic regulation and can result in a change in gene expression. Originally, the studies of inter-generational trauma effects were studied in the offspring of Holocaust survivors and the psychological symptoms they displayed.21 Later studies were expanded to the children of Vietnam veterans, Native Americans, and AAs.21 The transgenerational impact of past trauma perpetuates disparities in following generations through a combination of these epigenetic influences in addition to the present trauma experienced by these individuals due to racism and discrimination in today's society.13 It is possible for these epigenetic changes to be reversed by eliminating these stressors through targeted social interventions in which pharmacists could play a role.

4 | RACE AND ESTIMATING KIDNEY FUNCTION

Lack of trust in the health care system may also stem from the use of medical algorithms that include race. AAs have higher serum creatinine, on average than Whites in relation to their measured glomerular filtration rate (mGFR).23 Subsequently, the most common equations to estimate glomerular filtration rate (eGFR) in the United States (MDRD and CKD-EPI [2009] equations) include a race coefficient (AA and non-AA) to account for non-GFR determinants of serum creatinine that differ by race. This coefficient decreased bias in the estimated GFR (eGFR) as compared to mGFR in AAs.24 Although results from the CKD-EPI (2009) equation are statistically unbiased for AAs and non-AAs, at a population level it overestimates mGFR to a greater degree in AAs than non-AAs. The potential repercussions include delaying the detection of kidney disease and referral to nephrology for appropriate treatment or reducing eligibility for a kidney transplant, further exacerbating patient and practitioner distrust.25

Identification of kidney-disease-related disparities in AA (such as a lower likelihood of being transplanted) led to grass-roots efforts by medical and pharmacy trainees and providers to address kidney-related racial disparities within health care and health care curricula.26 Spurred by George Floyd's murder in 2020, there were further calls to action to address racism and racial health inequities in patients with kidney disease. The first issue that was targeted was the use of race (AA or non-AA) in eGFR equations. Several institutions independently decided to simply remove the race coefficient from these eGFR equations and report the non-AA results for all. These actions led to the rapid publication of several papers that showed that removing the race coefficient from CKD-EPIcr (2009) resulted in a large underprediction of measured GFR by
7 to
14 mL/min/1.73 m2 in AAs,27,28 which could potentially reduce some disparities in AAs (eg, earlier identification of kidney disease and placement on kidney transplant wait list) but create new disparities (eg, reduced initiation of life-saving chemotherapies and potential for inappropriate initiation, discontinuation or underdosing of many medications).29,30

A call for a re-examination of racial health inequities in clinical algorithms and medical care resulted in the formation of the National Kidney Foundation-American Society of Nephrology Taskforce to reassess the inclusion of race (AA vs non-AA co-efficient) in the estimation of GFR and its implications for diagnosis and management of patients at risk for or with kidney disease.31 The cornerstone of their process was the development of statements of evidence and value that addressed race, racism, inequities, and disparities in the diagnosis and care of AA individuals with kidney disease.31 Twenty-six different approaches to estimating or reporting kidney function were evaluated. Taskforce members agreed on six attributes, including diversity in equation development population, potential clinical consequences and equation performance, to be considered in evaluating each approach. The Taskforce ultimately recommended three non-race-based eGFR equations as part of a new approach to assessing kidney function for medical and medication-related decision-making.27,31 The process that the Taskforce used could be a template that the nephrology community as well as other societies could use to address other healthcare disparities.

5 | DISPARITIES IN KIDNEY-RELATED DISEASES

Other patient factors such as barriers to healthcare access, limited health literacy, and distrust of healthcare providers contribute to disparities in CKD. Provider factors include limited knowledge of CKD treatment guidelines, biases or assumptions about their patients' ability or desire to participate in their CKD care, and suboptimal communication and interactions with patients from diverse cultural backgrounds. These risk factors contribute to AAs being more likely to progress to ESKD than Whites, less likely to be under the care of a nephrologist before starting dialysis, and less likely to have a preemptive referral for kidney transplants.5

A higher prevalence of obesity in AAs has the potential to cause disparities in medication-related decision-making in these patients.32 Kidney clearance of medications correlates best with nonindexed GFR (mL/min). However, many practitioners use indexed eGFR results in mL/min/1.73m2 to guide drug dosage adjustments. The average body surface area (BSA) in the United States has risen along with the obesity epidemic. Using indexed eGFR results (mL/min/1.73 m2 ) to guide drug dosage adjustment instead of nonindexed results (mL/min) may lead to an increased risk of medication underdosing in overweight individuals. Compiled data from nine studies with a diversity of patients, including AAs, showed that those in the highest BSA group had an indexed CKD-EPIcr (2009) eGFR that was almost 20 mL/min/1.73 m2 lower than the gold standard nonindexed mGFR.33 AAs, overall, are at an increased risk of being overweight or obese compared, compared to Whites, but AA women, in particular, have the highest prevalence of obesity, which can potentiate medication-related disparities if indexed eGFR results are used to guide medication dosing.32

The obesity epidemic in America impacts all races, however, systemic racism has caused geographic inequality, decreased access to quality health care, and underdiagnosis of obesity in AAs.34 Neighborhoods which consist of primarily AAs are less likely to have access to healthy foods and more likely to be oversaturated with fast food restaurants that serve processed foods high in sodium and fat. In these same areas, quality health care is sparse and is even more limited by those who are uninsured. Although these factors lead to higher rates of obesity in AAs, they are less likely to receive a diagnosis of obesity compared to Whites thus resulting in inadequate education on the disease or treatment.34 Obesity leads to other chronic conditions such as hypertension and diabetes which result in worse health outcomes for AA patients.

Uncontrolled hypertension can lead to CVD and ultimately kidney disease. It is known that the prevalence of hypertension is highest in AA patients (41.2%) compared to all other ethnic/racial groups.3 There are significant disparities in hypertension control and hypertension-related mortality. Hypertension control rates in AAs and Whites are 48.5% and 55.7%, respectively. On average, AAs are more likely to receive combination therapy for hypertension compared to other ethnic/racial groups and have the highest average number of antihypertensive medications.35 Overall, antihypertensive agent prescribing patterns for AAs are notable for more diuretic agent and calcium channel blocker (CCB) prescriptions and less angiotensin-converting enzyme inhibitors (ACE-I). These patterns are consistent with the notion that AAs are less responsive to ACE-I agents, however, studies have found that there are similar kidney benefits from these medications as other ethnic/racial groups.36 Interestingly, once diagnosed with CKD and/or diabetes, AAs are prescribed ACE-I or angiotensin receptor blockers (ARB) at similar rates as white patients (71.5% vs 70.6%, respectively).37

AAs have significantly higher rates of type 2 diabetes (T2DM) than Whites (12.6% vs 7.1%) and are more likely to experience complications from the disease, including uncontrolled blood glucose, microalbuminuria, retinopathy, lower extremity amputation, and kidney disease.4 Of note, the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, which are recommended for use in patients with diabetes who would benefit from their kidney protective effects, is lowest in AAs, Asians, and females in addition to those with low income.38 If these inequities are not addressed, the disparities in kidney and cardiovascular outcomes may increase. Similar to hypertension control rates, Black, Indigenous, and Persons of Color (BIPOC) are less likely to reach recommended guideline goals for glycemic control than Whites.39 Blood glucose self-monitoring occurred less in AAs and Hispanics compared to Whites; however, when controlled for socioeconomic variables and access to care, there were no differences. Overall, there are clear disparities and barriers in diabetes management for AAs in regards to self-monitoring and outcomes when compared to Whites.

Healthcare professionals must be informed about the known racial, ethnic, and economic disparities in care for CKD and related diseases in order to adopt strategies to improve health outcomes in vulnerable populations. Historically, community interventions involving pharmacists have been extremely successful at improving the health outcomes of patients with kidney-related diseases. The Indian Health Service (IHS) recognized health disparities in their patient population and was successful in applying a population health and team-based approach to diabetes care.40 Focused efforts from 1996 to 2013 reduced the incidence of diabetes-related ESKD by 54%. Another example of a culturally specific, community-based intervention is a study of AA men who underwent hypertension screening in barber shops by barbers and pharmacists.41 Almost 90% of the intervention group attained blood pressure control after 6 months with a mean drop in systolic blood pressure of 27.0 vs 9.3 mmHg in the control group.

The COVID-19 pandemic has highlighted racial health disparities and the distrust people of color have in health care in the United States. Patients with CKD are at risk of experiencing more severe COVID-19 infections than those with normal kidney function.42 According to the CDC, AAs have the lowest COVID-19 vaccination rate.43 AA respondents, to a survey including 1950 adult participants in the United States, cited mistrust and misunderstanding as the reasons for forgoing the vaccine more frequently than other racial/ethnic groups. AA and Hispanic respondents reported that they would be more willing to receive the vaccine if it was endorsed by medical professionals in their same racial/ethnic group.44

Supportive Service:

Email:wallence.suen@wecistanche.com 

Whatsapp/Tel:+86 15292862950

Shop:

https://www.xjcistanche.com/cistanche-shop