Social Stress, Inflammation, and Chronic Kidney Disease Among African Americans
Phase: NA
Conditions: Chronic Kidney Disease
Sponsor: Emory University

10/10/2018, 1 
 
Study Title: Social Stress, Inflammation, and Chronic Kidney Disease among African 
Americans 
 
Short Study Title: Stress and CKD among African Americans 
 
NCT Number: NCT03387319 
 
 
Principal 
Investigator: 
 
 
 
Kimberly R. Jacob 
Arriola, PhD, MPH 
 
Professor  
Department of 
Behavioral Sciences and 
Health Education 
Emory University, Rollins 
School of Public Health 
 
 
1518 Clifton Road 
Atlanta, GA 30322 
Phone: (404)-727-2600 
Email: kjacoba@emory.edu 
Co-Investigators: 
 
 
 
Janice Lea, MD, 
MSCR 
 
 
Professor of Medicine  
Department of Medicine 
Emory School of 
Medicine 
 
 
1365 Clifton Rd 
Atlanta, GA 30322 
Phone:  (404) 778-5380 
Email: jlea@emory.edu 
 
 
Tené Lewis, PhD 
 
 
Associate Professor  
Department of 
Epidemiology 
Emory University, Rollins 
School of Public Health 
 
 
1518 Clifton Road 
Atlanta, GA 30322  
Phone: (404) 727-6706 
Email: tene.t.lewis@emory.edu 
 
Bradley Pearce, PhD 
 
Associate Professor 
Department of 
Epidemiology 
Emory University, Rollins 
School of Public Health 
1518 Clifton Rd NE 
Atlanta, GA 30033 
Phone: (404) 727-4914 
Email: bpearce@emory.edu 
Viola Vaccarino, MD, 
PhD 
 
Professor and Chair 
Department of 
Epidemiology  
Emory University, Rollins 
School of Public Health 
 
1518 Clifton Rd NE 
Atlanta, GA 30033 
Phone: 404-712-2679 
Email: 
viola.vaccarino@emory.edu 

10/10/2018, 2 
 
 
 
 
 
 
Other Study Staff: 
 
 
Nakeva Redmond, 
MPH 
Project Coordinator 
 
1518 Clifton Road NE 
Atlanta, GA 30322 
Phone: (404)-727-2386 
Email: 
nakeva.redmond@emory.edu 
 
Study Sites: 
 
 
Georgia Clinical & 
Translational 
Science Alliance 
(Georgia CTSA) 
 
Study Site 
Collaborator:  
Thomas R. Ziegler, MD 
Program Co-Director 
Georgia Clinical & Translational 
Science Alliance (Georgia 
CTSA) 
 
Email: tzieg01@emory.edu 
 
Emory University 
Hospital Midtown, 
Internal Medicine, 
Nephrology Clinic 
 
 
Study Site 
Janice Lea, MD, MSCR 
Practicing Physician, 
Nephrology, 
Emory University Hospital 
Midtown, Internal Medicine   
 
Email: jlea@emory.edu 
 
 
 
 
 
 
 
Sponsor: National Institutes of Health (NIH), National Institute of Diabetes and Digestive and 
Kidney Diseases (NIDDK) 
 
 

10/10/2018, 3 
 
Abstract 
Chronic kidney disease (CKD) is a global public health problem.  African Americans have a 
higher prevalence of late stage CKD than Whites and progress from early stage to late stage at 
a much more rapid rate.  Biomedical explanations for African Americans’ faster CKD 
progression prevail, with virtually no research attention paid to the role of social factors.  Stress 
related to discrimination is a particularly compelling area of study in light of strong evidence 
demonstrating its linkages to CKD risk factors such as hypertension, diabetes, and obesity. The 
proposed proof of concept study will recruit 100 African American patients (both with and 
without diagnosed CKD) to determine whether discriminatory stressors are an important risk 
factor for CKD-related physiological processes and kidney functioning. 
The long-term goal of this research program is to understand the impact of and pathways 
through which discriminatory stress contributes to CKD progression. The overall objective of this 
R21 application, which is the first step towards attainment of this long-term goal, is to obtain 
effect sizes for a larger prospective R01 and explore two hypothesized pathways (i.e., blood 
pressure reactivity and pathophysiological mechanisms) using a multi-method research design.  
This study will carry out the following specific aims:   
 
1. To examine associations between chronic stressors (i.e., discriminatory versus 
general), pathophysiological mechanisms (i.e., elevated inflammation and nocturnal 
blood pressure), and poor kidney functioning among 100 African American patients. 
a. Based on a cross-sectional research design, we hypothesize that chronic discriminatory 
stressors will be associated with poor kidney functioning independent of other chronic 
stressors as mediated by CKD-related inflammatory biomarkers and autonomic arousal. 
 
2. To examine the impact of acute stressors (i.e., discriminatory versus general) on 
short-term changes in CKD-related physiological processes (i.e., increases in 
inflammatory markers and blood pressure reactivity) in patients from aim 1. 
a. Based on an experimental research design, we hypothesize that discriminatory stressors 
will be more physiologically impactful than general stressors.  Outcomes include several 
critical CKD-related inflammatory biomarkers and blood pressure reactivity assessed at 
three time points during the experimental manipulation.  
Collectively, these outcomes are expected to support the advancement of science-based 
information about CKD that can be disseminated in order to improve health and quality of life. 
 
 
 
 
 
 
 
 

10/10/2018, 4 
 
I. 
Background and significance 
The Problem of Chronic Kidney Disease among African Americans 
Chronic kidney disease is a global public health problem that continues to increase in both 
incidence and prevalence, affecting more than 30 million adults in the United States.1 The 
prevalence of CKD significantly increases with age2 and is most commonly caused by diabetes, 
hypertension, and glomerulonephritis.3  The Kidney Disease Outcomes Quality Initiative of the 
National Kidney Foundation established a classification system for determining CKD severity by 
using glomerular filtration rate as the determinant for the level of disease4 (see Appendix 1).  
Based on this staging system, national prevalence data indicate dramatic increases in end 
stage renal disease (ESRD) from 1996 to 2013.5  Moreover there is clear and compelling 
evidence of racial disparities in ESRD:  African Americans have an ESRD prevalence that is 
almost four times that of Whites (5,671 vs. 1,432 per million population) and progress from early 
stage to late stage at a much more rapid rate.5-7 
The Project Will Improve Scientific Knowledge of the Role of Social Stress in CKD 
Scientific research to date has focused on genetic and biological explanations for African 
Americans’ greater prevalence of ESRD than Whites.  For example, African Americans have 
higher rates of diagnoses for the two leading causes of CKD (type II diabetes8 and 
hypertension9) as well as other dietary and lifestyle factors that contribute to the progression of 
CKD.10 Late referral to a nephrologist and socio-economic factors (including income and access 
to care) also explain part of the racial disparities in CKD progression.11-13  However, even after 
controlling for all of these factors, racial disparities in ESRD remain.12,14,15 Indeed, the growing 
literature on socioeconomic status (SES) is a platform to launch a conversation of the role of the 
social determinants of CKD progression,16 but it cannot be where the conversation ends in light 
of evidence that race moderates this relationship.  The relationship between SES and CKD is 
stronger for African Americans than Whites. 15,17 
The Need to Study Stress in Relation to CKD Rests on a Strong Scientific Premise 
Several empirically-based conceptual models that consider how socio-cultural factors may 
contribute to racial disparities in CKD have been published in the peer-reviewed literature over 
the past decade.10,14,18,19  For example, a conceptual model adapted by Norris and Agodoa10 
suggests the need to consider factors such as marginalization and discrimination, chronic 
stress, distrust, and neighborhood conditions to understand CKD outcomes.  A recent heuristic 
model developed by Bruce et al.19 seeks to integrate the socio-cultural factors hypothesized by 
Norris and Agodoa10 and Norris and Nissenson14 (e.g., stress, the social environment) with 
genetic, behavioral, and psychological factors and pathophysiological mechanisms to explain 
kidney outcomes.  The Bruce et al.19 model focuses on stress.  It argues for strong influences of 
social environment and psychological factors on stress, which in turn relates to behavioral 
factors and pathophysiological mechanisms (such as inflammatory cytokines20), which then 
contribute to CKD risk factors (hypertension, diabetes, and obesity), and ultimately kidney 
outcomes. (Note that whereas the original Bruce et al. model includes blood pressure as a CKD 
risk factor, because blood pressure is reactive to stress we study it as a pathophysiological 
mechanism and leave diabetes and obesity as the key risk factors.)  A strength of this model is 
that there is a large body of knowledge using rigorous research designs establishing certain 
critical pathways in other populations (e.g., research linking discriminatory stress to 
hypertension and obesity in healthy cohorts). 21-24  However, a major weakness is that the field 
has yet to embark upon empirical testing of other key pathways (e.g., research linking stress to 
kidney outcomes via the pathophysiological mechanisms proposed in this project) with few 
exceptions.25 

10/10/2018, 5 
 
The Project Will Improve Preventative Interventions to Delay CKD Progression 
The ultimate goal of the proposed study is not to reduce the experience of social stress at the 
population level per se, but to understand whether these types of experiences have a 
deleterious impact on CKD outcomes and/or physiological processes and design psychological 
interventions with these stressors in mind.  In this respect, experiences of racism and other 
social stressors are comparable to other forms of chronic (job strain, caregiving) or 
uncontrollable (breast cancer, loss, trauma) stress for which psychosocial treatments have been 
established.  Current interventions to delay progression of CKD focus primarily on nutrition, 
lifestyle, and medical management of blood pressure and glucose and albuminuria.  The 
proposed project establishes the need to determine whether stress reduction might also be an 
important target for future intervention.  
 
II. 
Goals/Aims: 
This proof of concept study will recruit a sample of 100 African American patients, 80 with 
diagnosed CKD with equal numbers across stages 2, 3A, 3B, and 4 and 20 with no CKD 
diagnosis, to determine whether discriminatory stressors are an important risk factor for CKD-
related physiological processes and kidney functioning in this understudied population (see 
Table 1).  
Drawing from a recent 
heuristic model by 
Bruce et al.,19 it is 
theorized that the 
relationship between 
stress related to 
discrimination and 
kidney outcomes is 
mediated by 
inflammatory cytokines 
and blood pressure 
dysregulation.  
Further, because 
discriminatory 
stressors often co-occur with other chronic stressors (e.g., financial stress, occupational stress, 
relationship stress, and parental stress) in African Americans, we will also determine whether 
discriminatory stressors are independent of these other types of stress.  The long-term goal of 
this research program is to understand the impact of and pathways through which discriminatory 
stress contributes to CKD progression. The overall objective of this R21 research project, which 
is the first step towards attainment of this long-term goal, is to obtain effect sizes for a larger 
prospective R01 and explore two of the pathways hypothesized by Bruce et al. (i.e., blood 
pressure reactivity and pathophysiological mechanisms) using a multi-method research design 
(i.e., both observational and experimental research methods).  The central hypothesis of this 
study is that discriminatory stress is associated with poor kidney functioning and two potential 
mechanisms leading to poor kidney functioning -- increased inflammation and blood pressure 
dysregulation-- among African Americans with CKD. Using a multi-method design, we plan to 
objectively test our central hypothesis by pursuing the following specific aims:   
Objective 1. To examine associations between chronic stressors (i.e., discriminatory versus 
general), pathophysiological mechanisms (i.e., elevated inflammation and nocturnal blood 
Table 1. Stages of CKD 
Stage 
Description 
Estimated GFR  
(mL per minute per 1.73 
m2) 
1 
Kidney damage with 
normal 
or increased GFR 
≥ 90 
2 
Mild CKD 
60 - 89 
3A 
Moderate CKD 
45 - 59 
3B 
Moderate CKD 
30 - 44 
4 
Severe CKD 
15 - 29 
5 
Kidney failure 
<15 (or dialysis) 

10/10/2018, 6 
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10/10/2018, 7 
 
 
A. Organizational Structure 
This study is funded by the National Institutes of Health (NIH), National Institute of Diabetes and 
Digestive and Kidney Diseases (NIDDK), and was developed by faculty in the Rollins School of 
Public Health. An internal medicine clinic within Emory University Hospital Midtown (at which 
Co-Investigator Dr. Janice Lea currently serves as a practicing nephrologist) and the Georgia 
Clinical and Translational Science Alliance (GCTSA) (for which Dr. Thomas R. Ziegler serves as 
Co-Director) will serve as study sites. Additionally, study participants’ bio-specimens will be 
analyzed at the Molecular Neuroimmunology Laboratory in the Department of Epidemiology at 
Emory. Bradley Pearce, PhD, who also serves as a Co-Investigator on this project, will oversee 
analyses of select blood samples. Outside laboratory resources will be used for processing and 
analyses of the remaining biospecimens.   
B. Setting and location 
This study will take place in Atlanta, GA, within a region characterized by high rates of CKD.28  
We will recruit patients seen at a single clinic located at Emory University Hospital Midtown 
where Dr. Janice Lea (Co-investigator) practices. This clinic serves patients along the CKD 
continuum as well as those with no CKD diagnosis. The five physicians in this clinic see 
approximately 150 African American patients per week demonstrating the feasibility of recruiting 
100 patients in eight months. Our prior experience conducting clinical studies suggests the 
importance of educating clinic staff about the study so that they can assuage patient concerns 
about participation. However, their involvement in the recruitment process is minimal, is not 
coercive, and does not undermine the voluntary nature of study participation.   
C. Population to be studied 
Inclusion criteria are as follows: 
• 
Patient at Emory University Hospital Midtown 
• 
Self-identify as African American or Black 
• 
Age 25 to 65 
• 
eGFR ≥ 15, or <90 
Exclusion criteria are as follows: 
• 
Mental disorder that prevents the completion of the Computer Assisted Personal 
Interview (CAPI) and the stressful recall manipulation 
• 
Currently on maintenance dialysis 
• 
Unable or unwilling to undergo intravenous catheterization 
 
 
D. Recruitment 
Study participants will be 100 African American adult aged 25 to 65 receiving services at Emory 
University Hospital, Midtown.  Of these, 80 will have a CKD diagnosis and 20 will not.  We will 
rely heavily on recruitment strategies that have been successful at recruiting African American 
patients into other clinical studies.29,30 Initially, clinic staff will identify potential participants 
through the clinic appointment system, including those who meet the inclusion criteria through a 
preliminary review. The clinic staff will share this list with the study project coordinator, who will 
mail potential participants a letter inviting them to participate (see attached for sample letter). 
The letter will outline information about the study (including purpose and participant 
requirements), and interested participants will be instructed to contact the project coordinator to 

10/10/2018, 8 
 
learn more about the study. If he/she is interested in participating, he/she will have the 
opportunity to review specific participation requirements at their next appointment, or upon next 
visit to the clinic. Participants will provide consent and be enrolled in person. The second tier of 
participant recruitment will consist of the project coordinator using the potential participant list to 
call individuals who are patients in the clinic and potentially eligible for the study, and inform 
them about the opportunity to participate in the study. Those individuals who are interested in 
participating will have an opportunity to review specific participation requirements at their next 
appointment, or upon visiting the clinic, and will provide consent and be enrolled in person. 
Next, the project coordinator will provide clinic staff with a recruitment postcard (see attached 
example) which will be included in potential participant’s exit material after their doctor’s visit. 
The postcard provides study information, and instructs patients to contact study staff through 
email or phone calls if they are interested in the study. Finally, study recruitment flyers will be 
placed throughout the clinic (see attached for flyer example) and remain in the clinic until the 
conclusion of the study. The flyer provides preliminary information about the study, and instructs 
patients who may be interested in participating to call or email the project coordinator for more 
information. The project coordinator will provide further information about the study; those 
individuals who are interested in participating will have an opportunity to provide consent and be 
enrolled in person at their next appointment time.  We will continue this quota sampling and 
recruitment process until we have enrolled 20 participants in each of the five categories:  no 
CKD diagnosis and CKD diagnosis stage 2, 3A, 3B, and 4.   
Study enrollment will occur in person within the clinic. The previously mailed letter, phone call 
and posted flyers will serve as an initial introduction to the study. Upon study enrollment, we will 
work with clinic staff to verify stage of CKD diagnosis (where applicable) to ensure that we are 
achieving the desired quotas.  We will continue recruitment until the desired sample is achieved. 
 
E. Field Methods 
 
Data Collection Overview 
Study participation entails completion of a computer administered personal interview (CAPI) that 
assesses experiences of general and discriminatory stress, behavioral and socio-economic 
variables, and other psychological characteristics.  Upon completion of the CAPI, participants 
would be scheduled to attend a second session.  During this session the experimental 
manipulation entails them being asked to recall a general or discriminatory stressor (the 
participant is randomized to one of the two groups), while changes in blood pressure and 
inflammatory processes are monitored. Finally, participants provide blood pressure 
assessments over a 24-hour period using an ambulatory blood pressure monitor (ABPM). 
These methods are described below. 
Data Collection Procedures 
Day 1:  Consent, CAPI and 24-hour Ambulatory Blood Pressure Monitor (ABPM) 
Day 1 of data collection will occur at the Nephrology clinic within the Emory University Hospital, 
Midtown location. Those who consent to participate in the study will first complete a CAPI in a 
small private room at the clinic immediately following their appointment.  This is a self-
administered survey in which responses are directly entered into an iPad at the time of 
administration, thereby eliminating the need for subsequent data entry. REDCap software will 
be used to securely collect and manage CAPI-questionnaire data. The key advantages of this 
method include allowing the interviewer to answer respondent questions, probe for adequate 

10/10/2018, 9 
 
answers, and accurately follow complex instructions or skip patterns.31 The survey will assess 
participants’ experiences of general and discriminatory stress, behavioral and socio-economic 
variables, and other psychological characteristics. Participants will be paid a portion of the 
monetary incentive ($50) at the conclusion of the survey interview. The proposed CAPI-
questionnaire is attached.   
Prior to leaving the study site, the project coordinator will fit each participant with an ABPM, and 
provide detailed instructions on how to use and care for the device, (including removing the 
device for showering). Participants will also receive a handout of these instructions for reference 
at home (see attached). Participants will be asked to wear the ABPM for 24-hours, beginning 
the time they leave the clinic. Participants will return the ABPM the following morning between 
9:00AM and 12:00 PM, or when their second day of participation is scheduled. Dr. Lewis (Co-
Investigator) has used this approach in a recently completed pilot study with African American 
patients. Her prior experience demonstrates good compliance with adequate data readings and 
the return of the equipment. Blood pressure readings will be taken at 30 minute intervals, except 
between the hours of 10:00PM and 8:00AM when they are taken at 60 minute intervals. All 
blood pressure readings between 10:00PM and 8:00AM will be considered nocturnal blood 
pressure. In addition, participants will be asked to record an anticipated time they fell asleep, 
and the time they were awake the following morning using a diary (see attached). These data 
will be used for further analyses of daytime and nocturnal blood pressure readings. Participants 
will be expected to return the ABPM on Day 2 of data collection, which will be scheduled for 1-2 
days from Day 1 of data collection using the CR-Assist appointment program.  
Blood pressure readings captured during participants’ 24-hour ABPM wear period will be 
reviewed once participants return the device. We anticipate these blood pressure readings to be 
beneficial knowledge to participants and their overall health plan, and as a result will 
retrospectively provide these readings to participants and their physician, as appropriate. The 
project coordinator will review all blood pressure readings upon return of the device, and relay 
all readings to Dr. Lea (Co-Investigator and nephrologist) for review. Potentially concerning 
readings (>170/110 mm Hg) will be flagged for immediate review, and Dr. Lea will contact 
participants with alarming readings by phone, as determined by her review. Participants with 
healthy / normal blood pressure readings may also benefit from this information, and as a result, 
will be notified of these numbers via mail from Dr. Lea along with information about what the 
readings mean for their health. All participants will have the 24-hour blood pressure readings 
incorporated into their personal health records; nephrology clinic staff will be responsible for 
integrating these numbers into participants’ electronic health records within the nephrology 
clinic. Practices for reporting blood pressure readings will be outlined in the participant consent 
form (see attached).  
Day 2:  Experimental manipulation & ABPM return 
Day 2 of data collection will take place at the Georgia Clinical and Translational Science 
Alliance (Georgia CTSA), Emory University Hospital Clinical Research site at the Atlanta 
Midtown location within a room with a door (see attached). All Day 2 data collection 
appointments will be scheduled between the hours of 9:00 AM and 11:00 AM to account for 
diurnal changes in inflammatory markers. First, participants will return the ABPM and the ABPM 
diary to the project coordinator.  
Prior to initiating data collection on Day 2, study staff will retrieve a History & Physical (H&P) 
form from the participant’s Emory physician. The H&P form is an official record of a physical 
from a physician, and must have been obtained within the past 30 days to confirm that patients 
are fit to participate in the study. Study staff will upload the H&P form into the CR-assist 
appointment system for easy retrieval at the participant’s next visit. Participants will be 

10/10/2018, 10 
 
instructed to bring a list of current medications and to indicate any medical conditions on a 
patient history form (see attached). We will document these medications and any reported 
medical conditions (in addition to any reported conditions on participants’ medical charts), and 
control for them in analyses.  
Participants will first provide height and weight measurements, a urine sample, and baseline 
blood pressure testing.  A research nurse will insert an intravenous catheter, and take an initial 
blood draw (up to 4 mL to measure A1C and up to 4 mL to measure creatinine) and allow for a 
30-minute habituation period so that the participant adapts to the indwelling catheter. Once the 
participant has adapted, participants will be asked to rate their level of distress using the 
Subjective Units of Distress Scale32 (SUDS). Participants will be asked to rate their level of 
distress on a linear scale of 0 to 100, with 100 being the highest. The nurse will take a blood 
draw (up to 6mL to measure inflammatory biomarkers and up to 4mL to measure eGFR).  
 
 
 
 
Next, participants will undergo a moderate psychological stress adapted from the commonly 
used Trier Social Stress Test (TSST)33. The TSST protocol has been adapted for use in 
recalling race-related experiences34 underscoring its appropriateness for our protocol. Dr. 
Vaccarino (Co-Investigator) and colleagues, have also used a similar experimental protocol and 
will provide related expertise for this project.35,36 Participants will be asked to recount one real-
life stressful situations; one event will be a stressful race-related event and one event will be a 
stressful event that is not race-related. We will randomize participants such that half will recall 
the racial experience and half will recall the non-racialized stressful event. Each participant will 
have an equal chance of being placed in the racialized or non-racialized experience group. The 
Project Coordinator will provide instructions using a script. Participants will be given two minutes 
to prepare their statement, and three minutes to deliver the statement. There will be an 
‘audience’ present at each participant’s speaking task. Aligning with previously conducted 
involving audiences33,35-38, each audience will include two observers who are of same race as 
the participant (African American), to heighten stress responses. Observers will wear white 
coats, and will be trained on the study protocol such that their behaviors are identical for each 
Figure 2. Day 2 Data Collection, Experimental 
Manipulation 

10/10/2018, 11 
 
manipulation task. The audience will be trained to remain neutral during the task, told to not 
show empathy and not to smile at any time during the test. Observers have not yet been 
identified, however once determined, the individuals serving as observers will obtain a CITI 
certification, and study staff will submit observer credentialing as amendment modification to the 
protocol. The project coordinator will also remain in the room while participants recall each 
designated stressful experience. Blood pressure readings will be taken every 1 minute during 
the participant’s preparation time and the actual recall task. The participant will be expected to 
use the entire three minutes for recall in each exercise; the project coordinator will cue the 
participant to continue until the 3-minute mark via standardized prompts from a script. 
Participants will be asked to rate their level of distress caused by the stressful event using an 
adapted version of Cooper’s racism recall scale.34 and again rate their level of distress on a 
linear scale (0 to 100) using the SUDS32. Participants will undergo a 45-minute recovery period 
after the first recall task; blood pressure readings will be taken every 5 minutes during this 
period. Immediately following the first 45-minutes of recovery, participants will provide a third 
blood draw (6 mL). Participants will undergo another 45-minutes of recovery, and provide and 
one final blood draw (6 mL) at the conclusion of the recovery period.  
Over the course of the study, participants will provide 3, 4 mL samples of blood and 3, 6mL 
samples of blood. A total of up to 30 mL may be taken over the course of the study. The project 
coordinator will debrief participants on the purpose of the experimental manipulation and 
common reactions to it. Participants will also be debriefed on the entire experimental 
manipulation experience, including the audience’s purpose. Participants will be paid $150 at the 
conclusion of Day 2 ($50 for return of ABPM and $100 for completion of experimental 
manipulation). The experimental protocol along with data time points are outlined in Figure 2.   
 
Data Sources  
Participants will be asked to provide data from the following sources: 
• 
Cross-sectional survey data that are provided by completing the CAPI (see attached) 
• 
Medical chart data, used only to verify their last eGFR in order to achieve equal 
numbers of participants by study stage/CKD diagnosis  
• 
Biological data in the form of blood and urine in order to assess kidney functioning and 
inflammation 
• 
Biological data in the form of height, weight, and blood pressure to assess standard 
control variables (i.e., Body Mass Index) and blood pressure reactivity 
Table 2 below lists the key constructs that will be measured, how they will be assessed, and the 
data source.  
Table 2:  Key constructs, measures, and data sources 
Construct* 
Measure 
Data Source 
Study Aim 1 (Chronic General and Discriminatory Stress) 
Chronic General Stress 
Perceived Stress Scale, Financial stress, 
Neighborhood stress scales 
Cross-sectional survey 
(CAPI) 
Chronic Discriminatory 
Stress 
Everyday discrimination, Major experiences of 
discrimination, Vicarious exposure to 
discrimination scales 
Cross-sectional survey 
(CAPI) 
Inflammation 
MCP-1,, IL-6, suPAR26,39 
Baseline blood draw 
Autonomic arousal 
Nocturnal blood pressure 
ABPM 
Kidney functioning 
eGFR based on the abbreviated Modification 
of Diet in Renal Disease study equation40,41 
Baseline blood draw 

10/10/2018, 12 
 
Kidney functioning 
Proteinuria based on the albumin-creatinine 
ratio42 
Baseline urine sample 
Study Aim 2 (Acute General and Discriminatory Stress) 
Subjective ratings of 
distress 
Subjective Units of Distress Scale (SUDS)32  
Cross-sectional survey 
(SUDS) 
Subjective ratings of 
recall distress 
Cooper’s Racism Recall Scale34 
Cross-sectional survey 
Inflammation 
MCP-1, IL-6, suPAR26,39 
Blood draw at 2 time 
points 
Autonomic reactivity 
Blood pressure  
Blood pressure reading 
 
 
Research Instruments and Assessment 
 
i. 
Chronic General Stress.  The Perceived Stress Scale (PSS) assesses different areas 
of life stress (e.g., overall stress, financial stress, occupational stress, significant other 
stress, parental stress, and stress within friendships). Moreover, the PSS has 
documented validity and reliability, and is short (14 items) and easy to administer.43 A 
total score is derived by summing responses to all items, with higher scores indicating 
greater perceived stress. The Financial Adjustments and Can’t Make Ends Meet scales 
by Conger and Elder 44-46 will be used to measure financial strain and stressful financial 
events. 45-47 The Can’t Make Ends Meet scale assesses the overall feeling that financial 
resources are insufficient (e.g. “During the last 12 months, how much difficulty have you 
had paying your bills?”); while the other scale captures adjustments made due to 
inadequate finances (e.g. “postponed medical or dental care to save money”). Ongoing 
stressful life events were measured using the Chronic Burden scale by Bromberger48.  
 
ii. 
Chronic Discriminatory Stress.  Based on recent recommendations,49 we plan to 
assess discrimination comprehensively, via multiple measures.  Exposure to “everyday” 
forms of discrimination will be assessed with the Detroit Area Study (DAS) Everyday 
Discrimination Scale 50, adapted by Dr. Lewis and colleagues. This scale asks 
participants to indicate the frequency with which they experienced various forms of 
interpersonal mistreatment in their day-to-day lives over the previous 12 months.  A 
single attribution item assesses the main reason for these experiences.51 The Major 
Experiences of Discrimination scale and Vicarious Exposure to Discrimination using 
modifications made in prior studies 52,53 measures experiences of unfair treatment over 
the lifespan in domains such as employment, police interactions, housing, and 
healthcare. Additional attribution items assess the reasons for these experiences (e.g., 
race/ethnicity, gender, education).51  
 
iii. 
Inflammatory Markers. The inflammatory markers were selected based on our own 
pilot studies, their sensitivity to acute stress induction 54,55 and strong associations with 
CKD. 26,56 The initial measure of inflammation will be based on the baseline blood draw. 
Plasma samples will be stored in -80oC until used for analysis in duplicate. To quantitate 
levels of IL-6 and MCP-1, we will employ the MesoScale system (MSD Rockville, 
Maryland) according to the protocols supplied by the manufacturer, which includes 
generation of a 6-7 point standard curve with standards validated by the company. The 
MSD system uses electrochemiluminescence for high sensitivity with a dynamic range of 
0.06–488 pg/mL for IL-6, and 0.09–375 pg/mL for MCP-1. For suPAR we will use the 
Virogates (CEDARLANE Laboratories, Burlington, NC) suPARnostic® ELISA according 

10/10/2018, 13 
 
to the protocols supplied by the manufacturer. This assay has a high sensitivity (0.1 
ng/mL) giving consistently quantitative results in plasma samples. 
 
iv. 
Autonomic Arousal. Ambulatory Blood Pressure (ABP) will be assessed over 24 hours, 
using the SpaceLabs model 90217 (Issaquah, WA), a small, noninvasive device.57 
Patients will be fit with the monitor and trained on proper application and removal 
techniques.  They will wear the monitor for up to 24 hours, removing it only to shower or 
bathe.  Prior to fitting the monitors, patients will be asked about their regular sleep and 
wake times, and monitors will be programmed to record systolic (SBP) and diastolic 
blood pressure (DBP) every 30 minutes during the day and every 60 minutes during the 
night.  Patients will be provided with a bedside diary, to record actual sleep and wake 
times, and any medications taken.  Following the ABP assessments, BP readings will be 
screened, and values that are ±3 standard deviations from the participant’s individual 
mean will be deleted.  Remaining valid values will be used to compute average daytime 
and nighttime SBP and DBP for each patient.  Note:  Because nocturnal BP is believed 
to be the most deleterious for later outcomes,58 our aims do not include BP dipping as a 
primary outcome; however, BP dipping will be assessed and analyzed in exploratory 
analyses, as detailed in Gallo et al.59   
 
v. 
Kidney Functioning.  We will use eGFR to measure kidney function using the 
abbreviated Modification of Diet in Renal Disease study equation as is 
recommended.41,42  Thus, we will measure serum creatinine from a baseline blood draw.  
Along with age, gender, and race, this information will be used in an online GFR 
calculator that is made available by the National Kidney Disease Education Program.  At 
baseline, participants will provide a urine specimen so that we can determine the 
protein/creatinine ratio.42 
 
vi. 
Covariates. Covariates to be assessed include behavioral factors (e.g., smoking, 
alcohol use, unhealthy diet, physical activity), socio-economic factors (e.g., health 
insurance status, income, and education), psychosocial factors (e.g., depression, quality 
of life), comorbidities (e.g., health conditions, medications, blood glucose control 
measured via HbA1C, and ApoL1 status), and demographics such as age, sex, and 
body mass index.  Depressive symptoms will be assessed with the Beck Depression 
Inventory (BDI),60 which is a self-administered 21-item scale that has acceptable 
sensitivity and specificity with regards to a clinical diagnosis of depression, and also 
provides a continuous measure of depressive symptoms. We will also assess previous 
self-reported diagnosis of major depression and previous use of antidepressant 
medications in addition to kidney disease quality of life.61 
 
 
vii. 
Acute vs. Discriminatory Stress Experimental Manipulation. At the end of the rest 
period, patients will asked to recall a personally relevant stressor, involving a general or 
racism-related stressful experience. Participants will be randomized into one of the two 
recall groups.. In the general stress protocol, participants will be asked to give a detailed 
account of a stressful experience (non-racial in nature) in which they felt so upset, angry, 
or annoyed at the time that talking about it during the clinic visit might still be upsetting to 
them.  In the racism recall protocol, patients will be asked to provide a detailed account 
of a stressful experience involving racism-- one where they were so 
upset/angry/annoyed at the time that talking about it during their visit might still be 
upsetting to them.  In both scenarios, patients will be asked to visualize the situation and 
recall the details of what happened, including: 1) where they were; 2) who else was 
there; 3) what was said and done (by the participant and by any other individuals present 

10/10/2018, 14 
 
at that time; 4) how they felt at the time and 5) the most stressful/upsetting aspect of the 
experience.  Patients will be given 2 minutes to prepare and 3 minutes to recount their 
experience for either the racial and non-racial stressful experience.  This protocol has 
been used in other studies of African Americans 34 and is adapted from a widely used 
mental stress protocol used in studies of anger.62,63 
 
Subjective Ratings of Distress.  In order to enhance the scientific rigor of this study, 
we will conduct a manipulation check to determine whether the experimental 
manipulation had its intended effect on study participants.  Thus, subjective levels of 
distress will be measured immediately before and after the recall task.  Using the 
Subjective Units of Distress Scale32 patients will be asked to rate their level of distress 
on a linear scale of 0 to 100, with 100 being the highest. Participants will also be asked 
to assess their level of stress directly related to reliving the stressful experience using an 
adapted version of Cooper’s Racism Recall scale34.Patients will rate their level of 
distress at the time of the event, and currently while thinking about the event on a linear 
scale of 0 to 10, with 10 being the highest.  
 
viii. 
Inflammatory and Blood Pressure Reactivity. Levels of inflammation will be 
measured at three time points during the experimental manipulation (immediately before 
the experimental manipulation, 45 minutes after the manipulation and 90 minutes after 
the manipulation) as shown in Figure 2.  A description of the inflammatory markers is 
provided above under “Aim 1 Assessments”.  Systolic and Diastolic blood pressure will 
be assessed every 5 minutes during the rest and instruction period, every minute during 
the preparation and recall task, and every 5 minutes during recovery, as shown in Figure 
2.  Mean scores for rest, recall task, and recovery will be calculated by averaging the 
readings taken during each period.  Blood pressure reactivity will be a change (or delta) 
score, calculated as the mean of the scores during the recall task minus the mean of the 
scores during rest, designed to represent the change in blood pressure induced by the 
recall task.  
Overall Time Burden 
Study participation occurs over the course of 2 days (Day 1=consent, CAPI and 24-hour 
Ambulatory Blood Pressure Monitor (ABPM); Day 2= experimental manipulation and ABPM 
return). Those who agree to participate in the study will be consented at the clinic and asked to 
complete the self-administered survey with responses entered into an iPad (approximately 1 
hour). At the conclusion of Day 1, participants will be fitted to wear ABPM assessing their blood 
pressure over 24-hours and asked to return the device to the study site upon return for Day 2 of 
data collection. In the second session, participants will provide a urine sample and undergo 
baseline blood pressure testing.  A research nurse will insert an intravenous catheter (allowing 
for a 30-minute habituation period so that the participant adapts to the indwelling catheter) and 
take a baseline blood draw. Participants will also be asked to recall a racial or non-racialized 
upsetting experience (approximately 3 hours). In total, participant time burden is approximately 
4.5 hours, plus the 24-hours wearing the ABPM. 
 
Storage of Biological Samples 
Biological samples will be analyzed for blood biomarkers relevant to psychosocial stress and 
kidney disease in the laboratory of Dr. Pearce.  In order to protect privacy, all samples will be 
assigned an identification number that does not include personal information. After samples 
have been centrifuged, the plasma, serum and buffy coat will be aliquoted and stored at -80oC. 
The sample ID will be barcoded and this barcode and sample ID will be used to label stored 

10/10/2018, 15 
 
aliquots.   If any samples remain after analysis, they may be stored under the control of the 
Kimberly Arriola, PhD (PI) and Brad Pearce, PhD (Co-Investigator).  
 
The samples will be stored for as long as they are useful, unless the participant asks us to 
destroy their sample sooner. If a participant chooses to have his/her sample material destroyed, 
he/she can do so by contacting Dr. Kimberly Jacob Arriola, who will provide Dr. Pearce with the 
required study and subject numbers. Any remaining blood samples will be located and 
destroyed. The PI will provide written confirmation that the sample was destroyed to the 
participant. The samples will not be distributed to anyone outside the immediate study team 
without express approval from IRB.  
 
F. Informed Consent Process 
The consent process will be conducted in-person by the study staff, in a private location near 
the waiting room in order to maximize convenience and privacy for the participant. An IRB-
approved written informed consent will be obtained from each participant at entry into the study; 
elements of informed consent will include: (a) participant reviews the study consent form; (b) 
investigator(s) or study staff review the consent with participants to confirm understanding and 
answer any pending questions; and (c) participant signs the consent form once the 
investigator(s) or study staff are convinced that the protocol is understood. Key elements of the 
consent form describe the voluntary nature of study participation, clarification that the decision 
to join or not join the research study will not affect the participant’s status as a patient, and that 
participants are free to withdraw at any point in time.  The consent form includes a standard 
HIPAA Authorization document as well.  After signing the consent form, participants will be 
given a hard copy of the form for their own records. Please see the attached consent form for 
details.  
 
 
IV. 
Potential Risks/Discomforts to Study Participants and measures to prevent 
occurrence 
 
Possible risks are related to: 
1. CAPI:  Being asked questions about the stress in participants’ lives may cause them to have 
unpleasant and/or upsetting feelings.  
2. Intravenous catheter:  This can result in infection, bruising of the skin, or a blood clot in the 
vein. Participants may have some discomfort from the blood drawing.  The risk from blood 
drawing is minimal, but may include bruising and infection.  
3. Experimental manipulation:  Recalling an upsetting experience may be unpleasant. 
4. Blood pressure monitoring:  Wearing the ABPM throughout the day and night may be 
inconvenient for participants, and some people may experience sleep disturbance while 
wearing the device at night.  Some individuals might also experience some bruising where 
the cuff is located. 
 
V. 
Benefits 
Participants may not derive personal benefit from their involvement in this study. However, 
participants may find some of the information they receive from this study helpful. For example, 
participants will receive a detailed report of their nocturnal blood pressure after wearing the 
ABPM device. Participants with healthy reports may use this information to continue healthy 
practices, and participants with concerning reports may use this information to seek professional 

10/10/2018, 16 
 
counsel on how to improve blood pressure readings. Additionally, what we (the research team) 
learn from this study will inform the development of a program of research that generates new 
understanding of the role of social stress on chronic kidney disease progression.   
 
VI. 
Compensation for time and effort: 
Participants will be offered a $200 monetary incentive for completing the study all steps of the 
study. Study participation occurs over the course of 2 days. Participants will receive $50 for 
completing the CAPI; $50 for return of the ABPM and $100 for completing the experimental 
manipulation. If participants return on Day 2 without the ABPM, the $50 incentive for its return 
will be withheld until the equipment is returned. This methodology addresses concerns about 
participant fatigue by scheduling assessments over the course of several days. 
 
 
VII. 
Data Analysis: Data Management and Monitoring: 
We will minimize the risk of loss of confidentiality by keeping all hard copy documents in a 
locked file cabinet; soft copy files will be on a password-protected secure network drive.  The file 
that contains the crosswalk between participant identification codes and their names (allowing 
us to ensure that samples are properly matched with each other and with the questionnaire 
data) will be password protected, also on a password protected secure network drive, in order to 
prevent theft or loss of data. All survey data will be retrieved and stored using REDcap software, 
which is HIPAA-compliant.  
VIII. 
Plans for analysis, statistical and/or otherwise: 
 
The study team will conduct data analyses within offices of the Department of Behavioral 
Sciences and Health education at Emory University. All data will remain de-identified during 
data analyses to protect participants’ identities.  
  
A. Exploratory Analyses 
We will start by creating a data set that merges the survey data will all biometric data. 
Traditional data entry for the survey data will be unnecessary as data will be imported directly 
into SPSS from the REDCap software that houses the CAPI-questionnaire. Data will be 
cleaned, coded, and examined for any missing data or unlikely values. We will examine 
frequency distributions for all variables, with particular attention to variable ranges, missing 
values, and transforming variables as needed, depending on evidence of internal consistency 
within scales. Next, we will conduct exploratory analyses to determine whether participants with 
the different sequences (i.e. race-related recall first or second) differ on demographic, clinical, or 
behavioral variables. Specifically, we will use logistic models to regress recall sequence on all 
relevant variables. If significant differences are identified, we will conduct further analyses by 
stratifying by these particular variables and consider adjustment for these variables in our main 
analyses as described below. 
 
B. Main Outcome Analyses 
These analyses are driven by the two hypotheses stated above: (1) Chronic discriminatory 
stressors will be associated with poor kidney functioning independent of other chronic stressors 

10/10/2018, 17 
 
as mediated by CKD-related inflammatory biomarkers and autonomic arousal; (2) 
Discriminatory stressors will be more physiologically impactful than general stressors on critical 
CKD-related inflammatory biomarkers and blood pressure reactivity. 
 
The first hypothesis is a meditational hypothesis.  We recognize that Baron and Kenny64 
methods for testing mediation are among the most widely cited, but also acknowledge that there 
are convincing critiques of this approach such as the requirement that there be a significant 
direct effect of the independent variable on the outcome in order to proceed with meditational 
analyses.65,66 Thus, we will use meditational methods proposed by Zhao et al65 that entail first 
running the Preacher and Hayes67 SPSS syntax commands to generate “bootstrap” results for 
the indirect effect of chronic discriminatory stress (controlling for general stress) on each of the 
two kidney outcomes (eGFR and proteinuria) through the inflammatory pathway as measured 
by each of the proposed biomarkers (MCP-1, IL-6, suPAR).  Bootstrapping relaxes assumptions 
about the shape of the sampling distribution of the indirect effect over repeated sampling from 
the population.68  These analyses will control for relevant covariates.  Next we will classify the 
type of mediation using the Zhao et al typology (complementary, competitive, indirect only, 
direct only, or non-mediation), and proceed with interpreting the findings in light of our 
hypotheses.  We will consider using structural equation modeling as another technique 
recommended to test mediation.69,70  
The second hypothesis will entail use of a 2X3 ANOVA to simultaneously test the main effects 
of stress recall (race-related or not) (discriminatory stress vs. general stress) and data collection 
time point (rest, stress, and recovery) on each of the outcomes (i.e., each inflammatory 
biomarker and blood pressure), also controlling for the relevant covariates.  This test provides a 
form of economy by examining multiple effects at a time, while also allowing us to study the 
interaction between study condition and time.71  
 
C. Statistical Power 
The proposed proof-of-concept study is designed to generate effect sizes to inform a future 
power analysis and thereby establish the legitimacy of studying this topic in a subsequent large-
scale clinical trial.  Thus, it is not intended to achieve the level of power to demonstrate 
statistical significance as is common in larger studies. Nevertheless, regarding study aim 1, if 
we were to perform a multiple regression with 8 predictors that explain just 15% of the variance 
in a given outcome, we would achieve 84% power at α=.05 
(http://danielsoper.com/statcalc3/calc.aspx?id=9) at N=100. For aim 2, collecting data at 
multiple time points is one way to maximize power.  If we just consider the two study groups 
(intervention and control) we would achieve power of .80 to detect a medium effect (.25) at 
α=.05 with a sample of just 64 participants.72 
IX. 
Training of study team 
 
All research staff maintains a current CITI, (Group 3 Social/Behavioral) certification. Proof of 
certifications has been uploaded for further review. Corresponding study team members 
(including members of the Georgia CTSA team and nurses within the Emory University 
Healthcare Nephrology clinic) will undergo study-specific training.  
 
X. 
Plans for monitoring the study for safety 
 

10/10/2018, 18 
 
The Data and Safety Monitoring Plan (DSMP) outlined below will adhere to the protocol 
approved by Emory University. An IRB-approved written informed consent will be obtained from 
each participant at entry into the study; elements of informed consent will include: (a) having the 
participant review the study consent form; (b) having the investigator(s) or study staff meet with 
the participant to review the consent, confirm understanding, and answer any questions; and (c) 
once the investigator(s) or study staff are convinced that the protocol is understood and that 
there is agreement to participate, having the consent signed. The principal investigator (PI) will 
review all data collection documents weekly for completeness and accuracy of the data as well 
as protocol compliance. The PI will review this protocol on a continuing basis for participant 
safety and include the results of the review in annual progress reports submitted to the IRB and 
the NIH.  
Patient Monitoring will be performed by the P.I., Co-Investigators, the Project Coordinator and 
medical staff present during the experimental manipulation. Also, H&P is required per the 
GCTSA protocol. 
Stopping Rules for Stress-Inducing Experimental Manipulation  
Absolute Indications for Termination  
• Drop in systolic blood pressure >10 mm Hg (persistently below baseline). 
• Technical difficulties monitoring blood pressure.   
Relative Indications for Termination   
• Increasing chest pain.   
• Participant becomes excessively anxious, uncomfortable, or requests to stop.  
• Fatigue, shortness of breath, wheezing, leg cramps, or claudication.   
• Hypertensive response (systolic blood pressure >200 mm Hg and/or diastolic blood pressure 
>92 mm  Hg).  
Patient reporting rules for blood pressure 
Dr. Lea (Co-Investigator and nephrologist) will review all participants’ blood pressure readings 
from the 24-hour ABPM task. Participants with healthy / normal blood pressure readings 
(readings ≤ 170/110 mm Hg) will be notified of these numbers via mail from Dr. Lea along with 
information about what the readings mean for their health. The project coordinator will 
immediately alert Dr. Lea of participants with blood pressure readings that may be concerning 
(>170/110 mm Hg). Dr. Lea will review associated readings, and notify the participants via 
phone at her discretion. All participants will have the nocturnal blood pressure readings 
incorporated into their personal health records; nephrology clinic staff will be responsible for 
integrating these numbers into participants’ electronic health records within the nephrology 
clinic. 
 
Patient safety data examination, monitoring procedures/oversight. All adverse events 
(AEs) will be graded as to their attribution (unrelated to protocol, or possibly, probably, or 
definitely related to protocol). Any AE that is reported to either the PI or her designated research 
associates by a study participant or by medical staff caring for the participant and which meets 
the criteria will be documented as such. Potential (“expected”) AEs are described above under 
“Potential Risks”. Serious adverse events (SAEs) are predefined as: any experience that 
suggests a significant hazard, such as events which: a) are fatal, b) are life threatening, c) result 
in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital 
anomaly, or drug overdose. The standard Emory IRB reporting guidelines for AEs and SAEs will 

10/10/2018, 19 
 
also be followed. The investigators and staff will report all AEs according to Emory IRB 
protocols and evaluate the SAEs, in close coordination with the Emory IRB. The IRB annual 
report from the PI will be stored as a hard copy file.  
 
Plans to minimize potential AEs are described above under “Adequacy of Protection Against 
Risks.”  
 
Plans for transmission of temporary or permanent suspension actions. Any actions that 
mandate temporary or permanent suspension of the study will be transmitted to the Emory IRB 
and, if appropriate, to the FDA and the National Institutes of Health.  
 
Plans for protecting participant confidentiality. Participants will undergo CAPI interview in a 
private room adjacent to the clinic waiting room.  They will undergo the experimental 
manipulation in one of six private research bays within the outpatient research suite of the 
Georgia CTSA.  All data will be collected by IRB-approved personnel.   All information and 
materials obtained will be used for research purposes only, and the data will be kept in strict 
confidence. Confidentiality will be assured by the use of participant codes rather than personal 
identifiers in all data collection forms, datasets, and reports. The study database will be secured, 
and information will be entered using participant identifier codes rather than personal identifiers. 
Only group data will be presented and published.   
 
Plans for assuring data accuracy and protocol human safety compliance. The above 
detailed plans should assure data accuracy and protocol human safety compliance for this 
study. These also include computerized database management and IRB oversight and 
communication. This plan, together with the monitoring by the IRB, should be sufficient without 
the addition of more faculty members to constitute a Data Safety and Monitoring Board.   
 
 
 
XI. 
Confidentiality 
 
Privacy will be maintained while individuals are participating in the study. Participants will be 
provided with a private room to provide consent and complete the CAPI instrument on Day 1, 
and will be provided with a private room to provide specimens and participate in the 
experimental manipulation on Day 2. Study participants' names will remain confidential.  Names 
will not appear in the data collection documentation. Informed consent documentation will be 
stored in a separate location from participant data. Thus, the data will not be linked to participant 
identifiers. When reporting study findings, identifiable information will not be used.   
 
The samples will be stored for as long as they are useful, unless the participant asks us to 
destroy their sample sooner. If a participant chooses to have their sample material destroyed, 
he/she can do so by contacting the PI (Dr. Kimberly Jacob Arriola) or the project coordinator 
(Nakeva Redmond). Participants will be informed that their data will be used for the current 
study, but removed for any potential use on future studies.  
 

10/10/2018, 20 
 
XII. 
References 
1. 
Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System—
United States. 2015; http://www.cdc.gov/ckd. Accessed December 10, 2015. 
2. 
United Stated Renal Data System. 2015 Annual Data Report Epidemiology of kidney disease in 
the United States Volume 1:  Chronic Kidney Disease in the United States. Bethesda, MD: 
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 
2015. 
3. 
Shafi T, Coresh J. Chronic kidney disease:  Definition, epidemiology, cost, and outcomes. In: 
Himmelfarb J, Sayegh MH, eds. Chronic kidney disease, dialysis, and transplantation:  Companion 
to Brenner & Rector's The Kidney. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2010:3-21. 
4. 
Patel SS, Kimmel PL, Singh A. New clinical practice guidelines for chronic kidney disease:  A 
framework for K/DOQI. Seminars in Nephrology. 2002;22(6):449-458. 
5. 
United Stated Renal Data System. 2015 Annual Data Report Epidemiology of kidney disease in 
the United States Volume 2:  End Stage Renal Disease (ESRD) in the United States. Bethesda, 
MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney 
Diseases; 2015. 
6. 
McClellan W, Warnock DG, McClure L, et al. Racial differences in the prevalence of chronic 
kidney disease among participants in the Reasons for Geographic and Racial Differences in 
Stroke (REGARDS) Cohort Study. Journal of the American Society of Nephrology. 2006;17:1710-
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