 Well, good afternoon, everyone. I'm Eric Green, Director of the National Human Genome Research Institute. I wanted to welcome you to the Genomics and Health Disparities Lecture Series. I'm just going to give a general introduction about the series, and then I'll turn this over to a colleague to introduce today's speaker. I just want to remind you, this is the second lecture in a series we have dedicated to looking at genomics and health disparities. The series is really designed to educate and to encourage conversations about how genomics research and genomic technologies can really affect health disparities research and opportunities we see going forward in this very important area. And we've deliberately selected speakers who will approach the problem of studying health disparities from different perspectives, from genomics research with an emphasis, but also making sure we've covered a full spectrum across the research landscape from basic science to population genomics, as well as translational and clinical research. Now reflecting the broad interest in this area, and our institute, NHGRI has been fortunate to have four co-sponsors to this lecture series, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung and Blood Institute, the National Institute on Minority Health and Health Disparities, and also the Office of Minority Health at the Food and Drug Administration, the FDA. Now the series started with the first lecture by Dr. Carlos Bustamante, a well-known population genomicist from Stanford University, whose research focused on analyzing genome-wide patterns of genomic variation within and between species and how that is used to address fundamental questions in biology, anthropology, and medicine. And today's speaker will very nicely compliment what we heard from Carlos, and I think again in many ways set up some of the issues and problems we'll be hearing about in subsequent lectures. So to introduce today's speaker, I'd like to turn the podium over to my good friend and colleague, Dr. Griff Rogers, who's the director of the National Institute of Diabetes and Digestive and Kidney Diseases, Griff. Well, thanks, Eric, and I'm certainly pleased to be here, and I want to welcome you to this lectureship series. It certainly gives me great pleasure to introduce my good friend and colleague to be a part of this session, Dr. Neal Poe. Dr. Poe earned his medical degree at Harvard's Medical School and his master's in public health at the Harvard School of Public Health. He subsequently went on to the University of Pennsylvania where he completed his residency and a Robert Wood Johnson clinical scholar, and during that period of time received an MBA degree at the Wharton School at Penn. And after spending many years at Johns Hopkins where he was ahead of the Welch Center, Dr. Poe moved to San Francisco where, as you can see, he is the chief of medicine at the Priscilla Chan and Mark Zuckerberg San Francisco General Hospital. That's important to point out. He's also the Constance B. Wolfe Distinguished Professor and Vice Chair of Medicine at the University of California at San Francisco. Dr. Poe's research unites medicine and public health with the goals of saving and improving the quality of human lives. And his major interests have been in improving discovery, education, and clinical practice of medicine, propelling academic organizations to function effectively and efficiently in developing future talents and leadership in the health profession. And this is actually where we work very closely together in the current Harold Amos Medical Faculty Development Program, the erstwhile Robert Wood Johnson Minority Medical Faculty Program where I've worked with Neil for going on 20 years now. Dr. Poe is remarkably creative and innovative thinker in the area of kidney disease and public health, looking at many different factors, including the role of race and gender in treatment settings. One of a recent paper, a JAMA paper that he published entitled, Why Don't Physicians Follow Clinical Practice Guidelines? It's a framework for improvement that he published in 1999 has over 3,000 citations. In addition, Dr. Poe was part of a team that discovered the genetic variant on chromosome 22 that confers a significant risk of kidney disease and it's found exclusively in individuals of African origin. He continues to study this APOL-L1 gene and its role in ESRID or in-stage renal disease in health disparities. Dr. Poe has been a recipient of numerous NIH grants and has received many honors and awards. Just to name a few, he's a member of the National Academy of Medicine, the erstwhile IOM, he's a master of the American College of Physicians. He's received the Diversity Award from the Association of Professors of Medicine, the John M. Eisenberg Award for Career Achievement Research from the Society of General Internal Medicine and the Belding Scribner Award from the American Society of Nephrology. My colleague Dr. Greene mentioned that at least at the NIH, this series is co-sponsored by four institutes and I'm pleased to say that all four institute directors are here present at your talk. So without further ado, please help me in welcoming Dr. Poe for this lecture. Thank you, Griff. It's always nice when you've known somebody for over 40 years and they can give that kind of introduction to you and I'm really glad he said the things I'm most proud of and didn't say the things that I'm not most proud of. So thank you, Griff. Thank everybody for attending. I want to thank the institute directors for sponsoring this session. And this is one of the first times I've been able to show this slide, you know, with the Zuckerberg San Francisco General as we're now known due to a generous donation, the largest donation to a public hospital in the country. So what I'm going to talk about is one of my favorite subjects and that is disparities from the viewpoint of chronic kidney disease. So I'm going to start with a case illustrating racial and ethnic disparities in kidney disease. And then I'm going to put forth a premise about disparities as a focal point in science and medicine. Talk about definitions and a framework for how I try to understand disparities and talk a little through the lens of my research on the science of disparities of why kidney disease occurs more often in minorities than hopefully we'll have, may have some time for questions at the end. So let me start with a case. This is a common occurrence of 46-year-old African-American male who presents to the emergency room for generalized weakness nausea and vomiting. His history of present illnesses had increased lower extremity edema for two months. He was seen by a private physician, a physician who cared for his mother. There was no lab work done, but he was placed on a diuretic. His edema improved, but worsening weakness and a 15-pound weight loss over two months. And then he presented to the emergency room with nausea and vomiting of three days duration. In his past medical history, he had no history of kidney disease or other chronic diseases. He did have a family history of diabetes and hypertension, and he took no medications, including over-the-counter medications. On physical exam, he was chronically ill-appearing. Young man in no acute distress. His vital signs were normally, notably his blood pressure was 141 over 76. And his exam was really unremarkable, but his laboratory examination was remarkable, in that he had a bicarbonate of 19, a anion gap of 28, calcium of 5.8, phosphorus of 13, at a high BUN in creatinine 240 and 28. And so he was admitted and seen by the nephrology service, and a temporary catheter was placed, and he was immediately started on hemodialysis. So what this case illustrates is an African-American patient with kidney failure, not uncommon in the late presentation for care, where there's little opportunity to prepare for kidney failure, an urgent initiation of hemodialysis, probably limiting optimal treatment for end-stage renal disease. So this is my premise, that science on disparities, clinical care with diverse patients and education about disparities, enhances all of medicine and human health. Why? It's because learning about disparities allows the examination of complex interactions that contribute, often unequally, for different clinical problems to human health. So interactions between biology and the environment, between environment and social conditions, between biology and social conditions. And so examining disparities allows us to look at a variety of different determinants of disease. I'd like to show this side about the racial and ethnic composition of the United States of California and then the hospital that I practice at. In the U.S. now, minorities make up about 31% of the population. And if you look at projections in 2050, minorities are projected to make up, be a majority of the population. We passed that in California in 2005, where minorities make up a large portion of the population. And that's even larger in the city that I practice, live in San Francisco. And then if you look at the population at my county hospital that serves the underserved, in fact, we have a very diverse ethnic group, almost 20% to 30% of the population in different ethnic groups. And so we do a lot of, we do clinical care, we do education to students and residents, and we do a tremendous amount of research on our diverse and vulnerable populations. So last year was a year of anniversaries. On December 1st, 1955, that was a year that I was born. I shouldn't tell my age and grister age, too, since I've known him for, well, Rosa Parks changed the course of history and inspired all of us by the steps that she took when she came in a bus. But it was also another year of anniversaries. In September of 1985, the U.S. Department of Health and Human Services issued the landmark Teckler Report. And I remember this because I was a fellow at that time. And it was an amazing report because I think for the first time it documented health disparities in the United States among racial and ethnic minorities. And it said disparities are in front both to our ideals and to the ongoing genius of American medicine. And so this report served as a driving force for entering health disparities and advancing health equity in America. There was very little disparities research before this report was issued, I think, going on in the whole country. So disparities, what do we mean by disparities? Disparity is a difference or a lack of equality. And the Institute of Medicine said that healthcare should not only be safe, effective, patient-centered, timely, and efficient, but also equitable. That is providing care that does not vary in quality because of personal characteristics, gender, ethnicity, geographic, location, or socioeconomic status. And race. I know this is an emotionally charged term in our society. Nowhere else in the world is, are we preoccupied with race. And these are different definitions of race. Webster's defines race as a group of people united or classified together on the basis of common history, nationality, or geographic distribution. And the Institute of Medicine defined race as a construct of human variability based on perceived differences in biology, physical appearance, and behavior, not a biologic reality. And then I'd like Mike Bamshad's definition of both, that information about genetic group membership captured by notions of race is in general less than that obtained by making inferences of ancestry from geographic or explicit genetic data. And this schematic shows what the thinking is on this, showing genetic relatedness among different ethnic groups. And I think showing that, in fact, we all are make up of different ancestry, whether that's African-American, European, or Asian ancestry. And what's really remarkable is that the genetic distance between individuals within the same population is larger than the genetic distance between individuals from different populations. So we are really all one and the same. So since the Heckler Report, there's really been a plethora of data that has shown that there's not an uniformity of health among racial and ethnic groups in the United States. If you look at life expectancy, the differences are about a 10-year gap for black men versus whites, five years different for women. The infant mortality rate is higher for blacks and Native Americans. The death rate is higher for a variety of diseases for blacks and Hispanics compared to whites. And for most ethnic minorities, they have higher rates of kidney failure as I'll talk about, and also many other diseases. And these disparities persist even after accounting for socioeconomic status for insurance, lifestyle factors, and clinical factors. And I'll show you some of the evidence where chronic kidney disease. And the toll is really that shown in this article by my former colleague Tom Levis and Darryl Gaskins that the kind cost of health inequalities and premature death in the United States were $1.24 trillion. I always like to say, you know, that could have paid for health care reform that $1.24 trillion. And this is a striking article that I thought published several years ago by Chris Murray who showed that we live in eight Americas and he investigated mortality disparities across races and counties and race counties in the United States. And so he looked at eight Americas, America at the top where Asians live, where the average income per capita is $21,000, and where 80% of folks completed high school and then looked at Northland, low income, rural whites, and you can see the average per capita income and percent completing high school. But you go all the way down the list and you see actually Western Native Americans per capita income, half of that of Asians or middle America. And the graduation rate from high school very low and then blacks in middle America and then blacks in southern low income rural communities, again, 10,061% completing high school and then high risk urban blacks. And strikingly, he looked at the mortality over many years in these groups and they're rated in the order that I've shown you. But striking that the urban blacks here at the bottom, you know, I'm sorry, here at the top, no, sorry, at the bottom had a lower life expectancy at birth. And this is true for, you can see this relationship across these eight Americas is similar for males as for females, although females having less mortality. So just looking at the impact, I think, both of race and of socioeconomic status in America. So let me turn to kidney failure area that I've worked a lot in. We know that kidney failure, end stage renal disease, that needs to be treated with dialysis or transplantation, some form of renal replacement therapy if you are to live is up to 2.9 times higher in racial and ethnic minorities. This is data from the United States renal data system. And it shows that in 2013, the incidence of kidney failure was 825 per million population in African Americans compared to 282 per million population in whites. And the mean onset of end stage renal disease is about five years earlier. So it strikes minorities earlier. And the rate is higher you can see in most minorities. That includes Native Americans and Asians, not as dramatic as an African Americans, and also higher in Hispanics. And it occurs earlier than in the Caucasian population. So why is this bad? Treating SRD is costly, both personally and financially. A age 50 to 54-year-old person, expected remaining lifetime in the general population is 30 years. But if you're a dialysis patient, it's eight years. Or a transplant patient, if you're lucky to get one, is 20 years. And the annual Medicare expenditures are, you can see, eight times higher for someone who is on dialysis than if you're in the general population. And quality of life is poor, although if you're lucky to get a transplant, it can restore quality of life compared to the general population. So there's really the need to preempt illness upstream through molecular knowledge, through clinical therapeutics and through behavioral interventions. And that's what I've been trying to do after studying ESRD for many years is to focus on chronic kidney disease. And one of the projects I'm involved in is the CDC surveillance project, CKD surveillance project that's sponsored by the Center for Disease Control, where we track kidney disease in the United States. So one in 10 adults have chronic kidney disease that we've shown from Ann Haynes. Over 20 million individuals in the United States have chronic kidney disease. And what we do is we chart statistics for the nation, including for healthy people, 20 on chronic kidney disease prevalence, incidence, awareness, risk factors, health consequences, quality of care, and how well our health system is prepared to care for individuals with chronic kidney disease. So we look at trends, and this shows data from the United States renal data system funded by the NIDDK on the incidence rate of ESRD by race. And you can see, we really thought there was a epidemic in the 1980s and the 1990s. But recently, it looks as if we've begun to make a difference. And in fact, this rate, the rate of ESRD is declining, although it is still dramatically higher in African-Americans compared to the general population. You can see down here lower. And we recently did some work that we presented to the Last American Society of Defrology, meaning to see if actually the prevalence of earlier stages of kidney disease, chronic kidney disease is defined by an EG estimate of glomerular filtration rate less than 60 or albuminuria, its prevalence was declining. And it looks as if actually that it is declining, although there's a concern here in this shown in a blue line that in African-Americans, that rate of decline has not continued. So one of the things that's interesting is I think we have no or very few therapies today. And I think this slide from the African-American kidney disease study, I like to illustrate that. And this was, as you know, an NIDDK funded study of African-Americans with kidney disease, early stage kidney disease, and it compared ACE inhibitors to non-ACE inhibitors. And here you see that during the trial, in fact, the rate of the endpoint, which was a combined endpoint of ESRD as well as death or doubling of searing creatinine, it was lower in the ACE group than the non-ACE group. But what happened after the trial is you see that more than 50% of individuals, despite being on ACE inhibitors, still progress toward the endpoint, showing that our therapies are really halfway therapies, if at all, and that there is a great need to identify why this happens and to develop therapies to prevent this. Recently, my colleague Carmen Peralta published a study that shows that actually the decline in early stage kidney disease at early ages is faster among African-Americans than whites. And this shows by age EGFR and the top line in blacks who have a higher EGFR is measured by a statin. But you see that this rate of decline is much greater in African-Americans. The slope here is greater than in whites over with aging, suggesting that, in fact, there is a higher rate of progression of disease among African-Americans. And a large study was done in Kaiser in Southern California and a large number of individuals, over a million individuals in Kaiser Permanente, where they followed, they measured actually individuals' kidney function at baseline and then followed them over several years, one, three and five years. And what they showed is that in both African-Americans and Hispanics, the odds of progression to kidney failure were higher. And for blacks, that's true at any entry GFR for Hispanics. It was high only for those individuals who had a lower GFR starting in Asians, even a suggestion of rapid progression. So this is what we think now is that the higher incidence of kidney failure among African-Americans appears due to a faster rate of disease progression rather than a greater prevalence of early stage disease, that in fact blacks are more likely to progress through damage and kidney failure. And the issue is what are the contributing factors to this acceleration? So I want to talk a little bit about that, about how I think the field has dissected these factors and I try to think of them as susceptibility initiation and progression factors that contribute to the excess ESRD incidence. They could be biological, environmental, behavioral, such as lifestyle or even the quality or adequacy of the medical care that we deliver. So let's talk about biology. Observations were made by investigators in the south and southeast United States and they went into dialysis units and asked 26,000 individuals who were starting dialysis in the southeast United States, do you have a first or second degree relative who was also being treated for ESRD? And they found that actually 22%, 23% of the individuals in dialysis units had a first or second degree relative. Huge, really, really huge, almost one in four, but that this was much more striking among African-Americans than among whites. And this was replicated about 12,000 U.S. residents from a larger number of states and, in fact, the rate was higher among African-Americans than among whites, although not as dramatic in this earlier study. So that raised the issue of genetic factors. And several years ago, it was 1995, we started a study called the choices for healthy outcomes and caring for ESRD study. And it was a national prospective cohort study comparing the effectiveness of hemodialysis and perineal dialysis. We had set this up to look at treatment, but we recruited an interesting population of a thousand new onset, probably the first study of new onset or incident adult ESRD patients throughout clinics in the United States. And we followed them for up to nine years. This has been a great study that we've had multiple grants and has supported a lot of individuals' careers. And my colleague, Joe Korosh at Johns Hopkins, had the wisdom in 1995 when we got this study started to set up a specimen far before this was popular. And so we did measurements of serum and plasma and DNA at multiple time points during the follow-up of these patients. And this allowed us to address a variety of factors, considering the choice study we've looked at, risk factors for prevention, diagnosis, etiology and genetics. That's what I'm going to talk about, the work that we've referred to in therapy, prognosis, CKD complications, access to care quality, and even resource use and cost. And so this is a study that my late colleague, Linda Cal, and also Roland Perrec, who's in Canada now, did in the family investigation of propoethy and diabetes research group, using data from choice. They did a case control design to look at associations of genetic markers with kidney disease and found that MYH9 locus was associated with non-diabetic end stage renal disease in African Americans. But as Griff said, he actually was wrong. We got it wrong. And in fact, a variety of other studies emerged also looking at MYH9, looking not only at non-diabetic kidney disease, but with focal segmental glomerular sclerosis, HIV associated in nephropathy, as well as hypertensive nephropathy, showing this association with MYH9. But I think more importantly, ApoL1, because what we found out is that the real culprit was the ApoL1 gene that is a 14.5 kilobase gene on chromosome 22. But it's located downstream of MYH9, in fact, was in linkage disequilibrium with MYH9, and encodes for a product that's 398 amino acids. And the mutant form, or the mutant alleles, actually confer a survival advantage against sleeping sickness, tropanosomiasis. But they also infer a risk of increased risk for non-diabetic kidney disease. The mechanism we don't understand, although there are a number of potential candidates out there. And this is the structure of the product of ApoL1. It's a 43 kilodoton protein, the apolipoprotein family. It's bound to circulating HDL particles. And what's interesting, it's expressed in various organs, including kidney, podocytes, renal tubular cells, and glomerular endothelial cells. And it's involved in the autophagy pathway. What's even interesting, if you look at where these mutant alleles are in the population in Africa, there's not quite one overlap, but it suggests that, in fact, the area where the setsi fly, the vector for sleeping sickness, is most prevalent. Suggesting that there was this selection factor for this mutant allele. And so other studies funded by NIDK, the Crick study and the Ast study, have shown that the powerful effect of the ApoL1 mutant alleles and CKD progression in longitudinal studies, following up from the case control studies, rapid case control studies that were done, showing that two copies, not one, but two copies of the mutant alleles confers risk. And this is true whether individuals have protein urea or don't have protein urea, a potent risk factor for progression of kidney disease. So I'll come back to that ApoL1 in a minute, but let's talk about environmental factors. Could they contribute? Several years ago, it was asked by Reynard Kington to get involved in a study in Baltimore funded by the National Institute of Aging called the Healthy Aging in Neighborhoods of Diversity Across the Lifespan. And we designed a study that went into neighborhoods in Baltimore, where we could recruit both whites and African Americans, but actually African Americans of higher socioeconomic status and white Americans of lower socioeconomic status, equal proportions to allow us to try to tease out the effects of biology and socioeconomic status and race. And my colleague at Hopkins Dietrich Cruz did this study that showed that individuals who had lower socioeconomic status were more likely to have chronic kidney disease than those with higher socioeconomic status. But this was really profound for African Americans than for whites. And so, you know, it shows that there's also a powerful effect of socioeconomic status, something that Paul Kimmel, I know Paul here has studied tremendously and cares a lot about. But there's also behavioral factors. And we did this study several years ago. Actually, Paul Eggers had a lot to do with this study because he worked at the then CMS and allowed us to link the NHANES survey with the Medicare registry to provide a longitudinal look at individuals of whether they progressed to kidney disease. And so, we did this study looking at race. And what this shows is the relative risk for blacks versus whites in progression of kidney disease. And if you control for age and sex, there was a almost threefold higher risk. But if you control for SES, you could explain about 12% of the excess risk. And then, if you controlled for other lifestyle factors like physical activity, BMI, alcohol and smoking status, you could explain about a quarter of the risk. So, in fact, not only socioeconomic status but lifestyle factors influenced the progression of kidney disease. And recently, we did, we used this kind of linkage study linking again NHANES study with the ESRD registry where we looked at the exposure of dietary acid load determined by a 24-hour dietary recall questionnaire. And we measured NHANES participants whether they developed ESRD over 14 years of follow-up. We had a variety of data to control for potential confounders. And I know this slide is busy, but I want to, I just want to illustrate and tell you what it shows. It shows that those who have a high net acid excretion or a high dietary load of high dietary acid load, blacks are much more likely than whites to have a high acid load. Mexican Americans as well. And those who are in poverty, this is the poverty income ratio, also have a high dietary acid load. That high dietary acid load is a diet that is not high in fruits and vegetables, but more in animal products. And it's also true that those of lower socioeconomics that's less than a high school education had a higher dietary acid load. But linking this to, let's see, to the ESRD registry, this is what we found that actually having a high dietary acid load was associated, this is a cumulative probability of ESRD, versus a low dietary acid load. So, in fact, both behavioral factors, including diet, may be an important risk factor for disease. Well, what about the quality and adequacy of CKD care? One thing is we know that having control of blood pressure helps to prevent progression. And so, this is a slide from N. Haynes in a study that we did looking at minorities in the U.S. with chronic kidney disease. And this shows the percentage of participants with uncontrolled blood pressure. And you can see that compared to whites, African Americans, shown here, either with CKD or without CKD, have higher levels of uncontrolled blood pressure. And this just makes it more dramatic if you use a stricter definition of blood pressure control, which some argue for in chronic kidney disease. So, in fact, how we treat individuals may also contribute to progression. So, back to this slide, then, if you look at care quality as measured by controlled diabetes, hypertension, cardiovascular history, or cholesterol, you can explain about a 33 percent of the excess risk reduction in the study that I showed you before. If you put all those factors together, we could explain over half of the excess risk, but there's still a considerable amount of risk that is still there. And maybe is that ApoL1 or other genes, could we have, if we had had data back then about ApoL1 in this study, could we have explained 100 percent? So, these are some questions to ponder. How much does ApoL1 or other genes contribute to the disparity in ESRD incidents between African Americans and whites? How important is this gene in comparison to other modifiable risk factors? So, other questions are, are ApoL1 risk variants more susceptible to known kidney injury agents? Do ApoL1 variants alter response to an environmental factor or to treatment? And I think most importantly, does knowing ApoL1 risk status lead to better outcomes? What can be done? Is better blood pressure control, diabetes, avoidance, and nephrotoxins, less acid diets? Would that, would that help in such individuals? And there are lots of controversies about the decision to be a live kidney donor and donor outcomes. And that's a cool issue of great import. What about the mechanism? Well, ApoL1 has an endogenous function, does ApoL1 have an endogenous function in the podocyte that's necessary to resist environmental stress and maintain podocyte health? And the path, could the pathways be dysregulating the presence of two risk variants where clinical disease manifests with the introduction of environmental stress? Could there be gene-gene interactions? That may explain that there, you know, there could be modifier loci that explain the difference between different kidney pathologies. And then gene environment interactions, so-called second hits, could it be viruses or antiviral pathway that might explain the gaps that we see in lifetime risks with individuals with the same genetic background? What about, is ApoL1, is the risk, does the risk come from circulating ApoL1 or ApoL1 expressed in the kidney? Is this apoptosis as a, as a mechanism in podocytes? Lots of, lots of information. I think these kinds of studies illustrate how we can learn from researching diverse race and ethnic groups. And this recent study I did with my colleague, or at least a thought piece with a Steben Bouchard illustrates that, you know, in breast cancer we've been able to show differences in Native American anstrestry at the estrogen receptor locus led to discovery of a genetic variant that was protective against breast cancer in Latinas. In heart failure we know the data about fixed-dose combinations of hydrolyzine and isosorbide dinitrate suggested that blacks, but not whites, had a significant reduction in mortality. The increased pre-term birth rate due to endocrine disrupting chemicals, it's more common among minorities. Stevens-Johnson syndrome, kidney disease as I mentioned, and then response to antiretroviral agents that may be due to differences in genetic polymorphisms in the cytochrome pathway. So these are the kinds of insights I think that diversity is teaching us about. What about, I want to talk a little bit about downstream where I did a lot of my early working quality and adequacy of CKD care. And this data came also from the choice study where we looked at in our cohort the timing of specialist evaluation in chronic kidney disease and mortality. And what we found is that over one third of black dialysis patients prior to ESRD received a late evaluation by a nephrologist. So this is white males 25% received a late evaluation, but 45% of black males received a late evaluation, 38% of black females and 30% white females. And in fact, others have shown as well as us that when you have a late evaluation, you're really poorly prepared for dialysis. Your nutritional status is reflected by serum albumin is worse when you have a late evaluation, your hematocrit is lower, and you're less likely to get therapy for anemia. So it's shown in a variety of studies now. And I think what was remarkable is that when we looked at whether you had an early intermediate or late evaluation, among African Americans having a late evaluation was seven times higher risk of mortality with ESRD. So why is this important? Because poorly prepared patients miss opportunities to make informed treatment decisions, treatments about hemodialysis or perineal dialysis and transplant. We saw that in the patient that I presented who was, I like to say, found in the emergency room rather than prepared for ESRD. And choice of therapy matters. The risk of death for hemodialysis for subterranean dialysis in the first year is equivalent. But hemodialysis may yield better long-term outcomes. More frequent dialysis at home may be better. And self-care modality has enhanced quality of life. And transplants yield better length and quality of life as I showed you earlier. Live donor transplants are better and preemptive transplants even better. And African Americans versus whites are less likely to be weight listed in transplanted. They're less likely to receive live kidney transplants, less likely to have knowledge of kidney replacement therapies, less knowledge of transplant prior to a dialysis initiation. They have lower health literacy and health literacy that's been associated with transplantation. And they're less knowledgeable when being evaluated for a transplant, even when knowledge is accounted for race differences. Well, the knowledge is accounted for race differences in transplant evaporate. So let me summarize. I know that's a lot of information. What I tried to show you was illustrate the African American patient with late presentation for care who had poor preparation for ESRD and had an urgent hemodialysis initiation. And treating disease at end stage is costly both personally and financially and limits access to optional therapies. And that biologic, socioeconomic, behavioral and clinical determinants conspire to compromise health and health care for minorities. And we need to develop and rigorously test interventions to address determinants to human health and learn how to preempt illness through molecular knowledge to therapeutics and behavioral interventions. And disparities research allows the examination of these complex interactions that contribute often unequally to health for different diseases. And so a growing proportion of Americans are not fully benefiting from clinical and biomedical advances since racial and ethnic minorities make up 40% of the United States population. And most physicians and scientists, including myself, are informed by research that it's extrapolated from a largely homogeneous population. And ignoring diversity of the U.S. population is a missed scientific opportunity to understand factors that lead to disease or health. And U.S. biomedical research in steady populations must better reflect the country's changing demographics. So that's my premise, that science on disparities, clinical care with diverse patients and education about disparities enhances all of medicine and human health. So thank you for your attention. Thank you for the heckler report issued by your department some 30 years ago that got us on this journey. Well, thanks, Neil, for that great talk. I would point out that actually this is a very timely march is actually National Kidney Month. And on March the 11th is World Kidney Day. So this is a very timely talk in this series. The only problem with that is Marvel would have given me heckle for that because it's devoted to children. I was going to say the theme this year is kidney disease in children. And I didn't say anything about children. All right, but we have time for some questions if there are some. Thank you, Neil. That was not only a lovely talk, but it was an extremely important talk, I think. I have a observation and a question. So the observation is that over the last probably decade, I've become increasingly interested in the prenatal environment and perinatal environment and the idea of malnutrition, poverty, maternal fetal dysfunction in setting up the idea of lower nephron number, which may be differentially expressed in different populations. And I think that's a very important consequence because CKD may actually start shortly after birth or at birth. So I think that should be added to your very beautiful presentation. I agree. It's a wonderful area. It's really been understudied. And for a variety of reasons, it's very hard to get information like that on a large number of individuals to look at this. But certainly an intriguing area, again an area that brings together both biology and environmental factors, some of which I try to lead to. So thank you. That's very important, I think, area for future discovery. Epigenetics in action, sort of. But the question is, and I know you've probably struggled with because I think people in the dialysis world have struggled with this for 30 years since Fritz Port's observation is that the survival in black Americans in the end-stage renal disease program on hemodialysis is superior to the survival of white populations. And I've often thought that this must be associated with psychosocial factors and differential perceptions of quality of life or other factors associated with families. But the two questions would be why is that only in this population, especially out of all the chronic diseases, and we haven't really licked the issue. I think there's an important biological interactive message there that we haven't been able to elucidate. And I'm wondering what your thoughts are about that. Right. So that's very interesting. What Paul's referring to is that an African-American patient who gets to ESRD has a far better survival than their white counterparts. Paradoxical. So, you know, I've done some work to try to look at this, and what Paul's saying is this actually environmental and socio-economic? We've tried to look at whether it's biological, whether in fact, you know, I remember several years ago I did a study to try to look at that those who actually get onto dialysis, is there selection? Maybe African-Americans with more comorbidity are left behind and didn't have an opportunity for a dialysis. But that's not true in our country because Medicare provided insurance for everyone to, if they develop end-stage renal disease to get dialysis. And we actually showed that using some data. And then there's the other side, which is our more African-Americans less likely, because they're less likely to get a transplant, does that mean that in fact, when you compare them to Caucasians, the Caucasians have more comorbid disease that were contraindications to a transplant, or at least there was some subtle selective factors for people who got a transplant, meaning that the African-Americans left behind may be healthier. And there's some suggestion of that, although not perfect. And then the other side, which, you know, I have not seen a lot of data about is the environment, or as you say, behavioral related issues that may affect human health in your survival to be on dialysis. It's something we don't understand, another area for right for discovery. It was a lovely talk. Thank you, Neil. Hello. Thank you so much for your talk. My name is Hayes Sedantes. I am a post-bac student and actually a prospect medical student. My question for you is knowing all of this information, you know, the correlations and the factors related to certain disease, and how health disparities is related to that. You know, as you mentioned in the end, how, for example, even though African-Americans are more likely to need a transplant, they actually have more barriers to receiving a transplant. This information, how can it actually translate into doctors actually providing better patient care? Well, you know, what's interesting is we've known a lot of this. I could have showed you a slide that showed those transplant disparities. It's been 10 years and we have not made any difference in who gets weight listed or who gets transplant. We tried to tinker a little with the factors in the weight listing algorithm. So, you're absolutely right. I think this is a failure. I think it's a failure of our profession to correct this because it shouldn't be that individuals have different selectivity and may have to do with how we evaluate individuals for transplant. We also know that for living-related donors that have showed you the data that actually shows that African-Americans have relatives who have kidney disease. So, maybe that limits the potential live kidney donors in their family or friends. And how do you factor that in? So, we have a lot of reflection to do and I think even more action to turn this around. Thanks for your question. Thank you. And I would say also that thanks for the wonderful questions I had. I met with some of the trainees here today that are doing really exciting work in different laboratories throughout the NIH and it was fabulous to hear all the wonderful and exciting areas that they're working. Hi, Dr. Bells. Thank you for your interesting talk. I was wondering after diagnosis or the beginning of dialysis in patients, do you know if there's a difference in how dramatic their lifestyle behavior changes after, you know, when they in conjunction with their diagnosis or beginning of dialysis therapy? And if so, if that makes a difference in their survival rate? Mm-hmm. So, if I got the question right, you know, after someone has had a serious illness, could there be differences by ethnic group and how you respond to that illness that leads to behaviors that may influence alcohol? I think that's understudied. I haven't seen work in that area. It's a good question. Yeah, like for example, if, you know, I know I'm going to get kidney disease, I'll probably start eating better or exercising far more. We do know that, yeah. And you'll get tortured to do that, too, by your doctors and your family, definitely. In fact, if you look at, you know, smoking rates, something that my colleague Aliceo said, if you look at smoking rates and chronic kidney disease, the more severe your kidney disease gets, the less people smoke. We've looked at that in national data. So, great. Well, thank you very much. Appreciate it.