Frank Maddux: Current equations that use serum creatinine incorporate age, sex and race to estimate measured glomerular filtration rate. Inclusion of race in these equations and other medical algorithms is facing increased scrutiny because race is a social, not a biological construct. Its inclusion may contribute to systemic racism in medicine. Today’s guest is nephrologist Nwamaka Eneanya, Assistant Professor of Medicine and Epidemiology at the University of Pennsylvania’s Perelman School of Medicine. She’s an advocate for eliminating race from the formula, and the author of a wave-making paper that helped propel the issue to a national stage. Welcome, Nwamaka. Thanks for being here.
Nwamaka Eneanya: Thanks for having me on, Frank.
Frank Maddux: I think we need to start with some basics. Tell us a little bit about how we measure kidney function, and what is the GFR?
Nwamaka Eneanya: Sure. So GFR is-- stands for glomerular filtration rate, and to put it simply, that is how we determine how well someone’s kidneys are filtering the blood of waste and excessive fluid. Now, to actually measure GFR is actually kind of difficult. You need to obtain a series of blood measurements, sometimes urinary measurements, and so you can imagine that if you need to make a medical decision or a clinical decision based on someone’s kidney function, that you could not do that and make a snap decision, and so eGFR equations were developed for clinicians to be able to assess someone’s GFR at the bedside, and they’re-- historically or how it was developed were these regression equations that, as you mentioned, incorporate age, sex, race and serum creatinine, to again, quickly assess how someone’s kidneys are functioning.
Frank Maddux: So race has been a qualifier in these equations throughout the origin of the equations or just at one point in time?
Nwamaka Eneanya: Since the first equation, which was the MDRD equation, that study was published in 1999, they incorporated race at the onset. Now, at the time, the investigators thought that it was a good thing to incorporate race. They found that incorporating race made the equation more statistically sound or accurate, and they found differences, systematic differences, between the black participants and the nonblack participants in terms of their serum creatinine levels. Black participants had higher serum creatinine levels compared to the nonblack participants at any given measured GFR, and so what they did to account for that increase in creatinine that they found for black participants was to introduce this black race multiplier, and so for the MDRD equation, that multiplier was 1.21, and subsequently, 10 years later, the CKD-EPI equation was published, and that multiplier was 1.16, and so what that does is to, when you’re looking at a lab report, is that black people have higher eGFR by either 16 or 21 percent, depending on what equation is used.
Frank Maddux: How do you think that actually impacts the understanding of what real filtration rates and creatinine clearance and kidney function actually measures? What’s it actually doing here?
Nwamaka Eneanya: The kind of issue with using race to lead clinical management, and using particularly black race, is that we know that there’s large inequalities or inequities when it comes to black people and CKD. We know that black individuals are less likely to see a nephrologist before they start dialysis. They’re also less likely to receive a kidney transplant, and the issue is that our international guidelines, KDIGO guidelines, recommend that care is received at certain GFR cut points. Now, they say GFR, but most people, like I said, don’t have access to measuring GFR, so they use eGFR, and KDIGO guidelines, for instance, recommend that a patient see a nephrologist if their eGFR is less than 30, and a patient can gain wait list time, kidney transplant wait list time, when their eGFR is equal to or less than 20. So for black participants where there’re already these large inequities, have to wait, right, to become more sick to see a nephrologist or to gain wait list time, and so we’re thinking that having a race modifier in these equations widens already existing inequities in care.
Frank Maddux: Tell us a little bit about how you think this will play out in the population of people that we take care of. Are we going to find that more of our black patients are in fact going to have lower estimates of kidney function and both get care sooner but also recognize that they need access to those things that delay progression and other such things at a little bit of an earlier time? Is that ultimately part of the goal?
Nwamaka Eneanya: Absolutely. So I was very proud to be a part of the American Society of Nephrology and National Kidney Foundation Race and eGFR Task Force, and as of last month, they recommended a brand-new equation, the CKD-2021 equation. I was an author on that New England Journal paper, and that is an equation that’s been developed without race. So it could be used broadly, for everybody, regardless of your racial or ethnic background, and we’re thinking that that kind of equation, of course, will lower systematically, in particular, black individuals who have used the race modifier. Their eGFR will now be lower. However, as you’re stating, that means that they could have access to nephrologists earlier, as well as to gain wait list time for kidney transplants earlier, and we think that’s a great thing, but we also want to make sure that people don’t think that removing race from eGFR equations will solve racial inequities in nephrology, and we really do need to keep our eyes focused on the social determinants of health that we know can really affect black individuals, Hispanic individuals, other minoritized individuals, and cause racial inequity. So this is the first step to making sure that there’s equal access to care and that racial bias is not introduced into clinical care, and so I think that’s a great first step to achieving health equity.
Frank Maddux: What will be the path to getting this new equation actually adopted? And there’s a bit of a task to overcome the legacy of both MDRD and the CKD-EPI equation. What do you think needs to happen?
Nwamaka Eneanya: So the task force recommended three kind of big things. One, immediate implementation of this new equation without race, but also two, to increase access to cystatin C. What they found, or what we found, were that the combination of creatinine and cystatin C is actually the most accurate equation, and so cystatin C has been another biomarker that’s been around for a long time that does not perform differentially across racial groups, and so we really need to do that to be sure that we’re really achieving the most accurate assessment of kidney function, and the third recommendation is to really focus on conducting and funding research that, again, focuses on other aspects of health inequalities in nephrology and health inequities. So I think, you know, we really need broad advocacy to push this equation in labs widely, and institutions. A lot of institutions had already made the change of removing race from their eGFR reporting, and now we just need to update systems with this new equation, which is actually not a hard thing to do. It’s just a quick programming thing. I think the lay media has done a good job of advertising this topic, and so actually patients are now asking their clinicians, you know, “How is race being used in my care? Are you using this new equation?” We’re hoping that that prompts clinicians who may not have the same access as some of these larger tertiary care centers to push their organizations to use the race-free equation as well.
Frank Maddux: That sounds great. Tell us a little bit about how you socialize this amongst both patients and the general public, and I know you’ve participated on a lot of forums in the last few months as a part of this process, but just describe a little bit about how we get the word out broader than just in our nephrology audience.
Nwamaka Eneanya: Sure. I think we need to think outside of the box, right. I think social media’s been a huge tool increasingly and more recently -- during the pandemic. I think a lot of people have used Twitter as a way to gain access to, like, for instance, COVID-19 information, vaccine information, testing, and so I am a big advocate of using social media. I’m active on Twitter. I’ve always tweeted messages about race and eGFR. I actually made a TikTok video, which, you know, that’s-- the younger generations use that, but that video that discussed race and eGFR went viral, and 28,000 views on Twitter, and so I have[AC1] patients that come to my office and say, “I saw your TikTok video,” or, “I saw you on ‘The Doctors TV Show.’” “Grey’s Anatomy” just did an episode on race and eGFR that people have been commenting on a lot, and so I think it’s getting out there as the social media platforms have been spreading the word, as well as the lay press, and now even TV, very popular, syndicated TV shows, are really putting the word out there.
Frank Maddux: We’ve got some new drugs in the armamentarium against CKD for both diabetics and nondiabetics, and I’m just curious that in this day and time where we’re trying to look at who’s a good patient for SGLT2 inhibitors and other such agents that are coming down the pipeline, I’m wondering if this dialogue around renal function assessment can’t actually also be a stimulus for people to be more aware that there are active treatments to slow progression than there used to be.
Nwamaka Eneanya: I absolutely think so. I think people are more aware that, “Hey, I could have kidney disease and not feel any symptoms,” in particular, if you have diabetes and hypertension. People are becoming more aware that this is a very serious problem that has classically been undertreated and we have these new agents. There are disparities, by the way, in the receipt of these agents among black individuals. For instance, I have published on that data as well, and so I think the awareness of eGFR equations is bringing a brand-new awareness of chronic kidney disease to the medical community and to patients. A lot of people have talked about how the change in eGFR may affect, for instance, eligibility for these medications. If your eGFR is too low, then you may not actually qualify for something like an SGLT2 inhibitor. However, what we do know, and some publications have published on this as well, is that there’s a significantly smaller proportion of individuals who have advanced CKD. Most individuals in the United States have early stage CKD, and so although we’re shifting eGFR downwards for black individuals with this new equation, some may not qualify for the SGLT2 inhibitors, but significantly more patients will have CKD and will qualify. So I think we need to focus on those individuals and progression of CKD among them.
Frank Maddux: What do you think the greatest influencers are of communities of color in both trusting the healthcare system and gaining access to the kind of knowledge that they need to ask these key questions that you’ve brought up, whether it’s about drugs that may be available, whether it’s about what their actual kidney function is, what can we do to foster that in society a little bit better?
Nwamaka Eneanya: I think we need to partner with community stakeholders. I think, you know, an effective strategy that we saw -- to really push the COVID-19 vaccines among communities of color where there’s historically been a lot of distress or poor access to healthcare was to partner with community stakeholders where we can get the message out and there’s already trust there between, for instance, religious institutions or communities-- community advocacy organizations, to partner with them, to help spread the message. I think it’s really hard for patients to get that message in a 15-minute visit or 20-minute visit. There’s so many things to focus on, so really partnering with those stakeholders can be effective, as well as diversifying our workforce. We really-- there’s been a lot of research that shows that racial concordance helps with communication, helps with trust, and so we really need to focus on building our pipelines and increasing the diversity of not only clinicians but our staff. That’s been effective as well for those who are on the front line and treating our patient population.
Frank Maddux: I can recall many, many years ago the power of one of my patients who was both a transplant patient and a pastor in a large church, and it was remarkable to me the effect that he had on promoting organ donation in the community and the recognition of sort of breaking down some of the myths related to organ donation, and so this concept that the religious community, the social community the people live in, I think, is vitally important in trying to figure out, “How do we actually break down some of the barriers of the way we communicate with people and some of the inherent barriers of trust that I think exist?”
Nwamaka Eneanya: I think a common theme that we’ve learned during the COVID-19 pandemic is meeting the patient where they’re at. For instance, Penn did vaccination drives and partnered with religious organizations, black churches, in west Philadelphia, where primarily the residents are black, and we went to high schools and we did the vaccine drives and we vaccinated thousands of individuals who likely would’ve not had access to that vaccine if they had to come, for instance, to the hospital. So I think thinking about that and ways that we can do medicine outside of the healthcare setting, of the historic healthcare setting, is very important as well.
Frank Maddux: I think our health equity discussions are really at the beginning and the estimated GFR in the equation and the removal of the race-based qualifier, I think, is really just the beginning of a conversation that needs to mature within our country, Any final thoughts sort of about the journey that we’re entering into or are already on but at the early stages of?
Nwamaka Eneanya: I think the important lesson here is that we should be thoughtful about how we use race and think about race inequities in our research, and all the way from the design of the research study to the reporting of the results is key, and bringing people to the table who have that expertise is really, really important so we don’t have unintended consequences of research that could, for instance, widen inequities in care. I think that’s one of the key lessons. The second lesson is bringing, again, the patient voice to the table. Now, patients have learned about race and eGFR later on and have felt very betrayed by that type of practice. We need to have more transparency with our patients about the type of practices that we’re doing to continue to foster trust in marginalized communities. I think that’s a other-- the other big piece, and the other thing I would say is, you know, really just doing collaborative research, again, and thinking about disciplines that have published on social inequalities for a long time, sociologists, anthropologists, is very important in the biomedical sciences, and so I think there’s the few lessons that we can learn going forward.
Frank Maddux: We’re very quantitative as a field, and to some degree some of the discussions that need to occur are qualitative in nature and qualitative research is one of the things that I think offers an opportunity to try to understand what are people saying, what are they thinking, what are their feelings about many of these issues? And as we’ve, in our company, have moved the lens from being focused on the successful treatment of a patient being dialyzed to the overall life of the patient and trying to help more and more patients avoid that end-stage kidney disease state, it strikes me that it’s really an important time for us to broaden the way we look at many of the questions.
Nwamaka Eneanya: Absolutely. I would agree.
Frank Maddux: I’m here with Dr. Nwamaka Eneanya, and she’s been central to our national discussion around removing the race-based qualifier in the estimated GFR discussion. Nwamaka, thanks so much for being here.
Nwamaka Eneanya: Thanks for having me.