Dr. Jay Wish (00:05): Hello, I'm Dr. Jay Wish, Professor of Clinical Medicine at the Indiana University School of Medicine in Indianapolis, Indiana. Welcome to this program titled Anemia of CKD, Are We Missing The Boat? Part of the Updates and Advances in Anemia of Chronic Kidney Disease series. Joining me today is Dr. Ellie Kelepouris, who is Professor of Clinical Medicine at the Perelman School of Medicine of the University of Pennsylvania in Philadelphia, Pennsylvania. Welcome, Dr. Kelepouris. Dr. Ellie Kelepouris (00:34): Thank you, Jay. It's a pleasure to be here. Dr. Jay Wish (00:37): Anemia is a common complication of chronic kidney disease, or CKB. It's estimated the prevalence of anemia patients with CKD increases as disease progresses, and about 50% of all patients with stage five CKD have associated anemia. This is episode number two in the six part podcast series on understanding and managing anemia in patients with CKD. In this episode, we will focus on gaps in CKD anemia care, including diagnosis and management. Dr. Kelepouris will discuss how to identify patients with CKD, that should be screened for anemia, and important steps in monitoring these patients. My first question is, what percentage of patients with CKD by stage have anemia, as defined by the World Health Organization? Dr. Ellie Kelepouris (01:25): The World Health Organization recently published a review of this topic, and anemia was twice as prevalent in people with CKD, almost 15% in the general population, Jay. The prevalence of anemia increased with CKD stage from 8.4% at stage one, to as high as 53.4% at stage five, prior to dialysis. They reported worldwide that 22% of CKD patients with anemia reported being treated for anemia within the previous three months, but a large percent of patients remained untreated. So it's very prevalent worldwide, as well as in the United States. And we know that the prevalence of anemia increases with stage of CKD, but a large percentage of the patients remain untreated. Dr. Jay Wish (02:19): For patients with non-dialysis dependent CKD, what percentage are actually receiving treatment with the various therapies including ESAs, erythropoiesis stimulating agents, iron, and red cell transfusion? Dr. Ellie Kelepouris (02:33): A recent publications by NIH of 1,580,000 patients with non-dialysis dependent CKD reported that almost 11,000 patients used ESAs, and a large percentage of them had a diagnosis of anemia at the time of initiation of therapy. So the three therapies for treatment of non-dialysis CKD patients with anemia remain IV iron, ESA treatment, erythropoietin agents and stimulating agents. And lastly, transfusions. If you look at the breakout of the percentage of patients, they really stratify according to insurance, as well. (03:21): And commercially insured patients with stage three to five non-dialysis dependency CKD, 9% of them received IV iron, 11% ESA, and a large percentage, 12% were transfused. A larger number of patients without Medicare coverage were transfused. Almost 22% of those patients received blood transfusions. And if you look at overall, the non-dialysis CKD population, 10% of all Medicare insured CKD patients per year really received blood transfusions. So it is really a large percentage that really are not being treated, with either ESAs or IV iron. Dr. Jay Wish (04:05): So what are the downsides of transfusion in this population? Dr. Ellie Kelepouris (04:08): Well, the downsides are... The first and most important one is that this is really rescue treatment only. It's not really treating the disease. It's not really elevating the blood count to a level that is consistent. So it's only rescue, it's very transient. Administration of blood transfusions may cause iron overload. Patients may have transfusion reactions and/or bloodborne infections. Clearly, when someone has an infection, they can't receive IV iron. If they do, it becomes disseminated. And importantly, in our patient population, patients become allosensitized to foreign antigens. And when you have this allosensitization, it becomes a barrier to renal transplantation, and that's really a very, very big concern for us. Dr. Jay Wish (04:59): So let's talk a little bit about iron therapy. It can be given both orally and intravenously. What do you see as the advantages and disadvantages of each? Dr. Ellie Kelepouris (05:07): Well, I think oral iron is the first step, at least with our guidelines say we should always try oral iron first. I think sometimes, the need for iron utilization for erythropoiesis is really overwhelmed, just by patients being treated with oral iron. I think intravenous iron is a much more effective way of treating, and it actually increases the hemoglobin concentration much more much quicker than oral iron does. Oral iron has side effects, such as constipation, and patients really don't like taking it. And with current formulations of iron, I think that the reactions, sensitivity reactions, have really decreased substantially. So I think IV iron is a very safe alternative to oral iron, if you really need iron utilization as a primary concern. Dr. Jay Wish (06:09): So do you think that intravenous iron therapy is underutilized in our non-dialysis CKD population with anemia? And if so, what are some of the barriers to its use? Dr. Ellie Kelepouris (06:21): Well, the benefits to oral and IV iron are obvious to everyone. Effective in absolute iron deficiency. It reduces the need for erythropoietin stimulating agents, in both dialysis dependent and non-dialysis dependent CKD. Oral iron is always the first step. IV iron is recommended, however, and I think it's maybe underutilized in our dialysis population. And the reason we need to use IV iron, I think the limitations is that oral iron may be really ineffective. You may not achieve the level of erythropoiesis with bioavailable iron. It could be poorly tolerated. GI-related side effects are really common complaints from patients. And IV iron has been known to cause hypotension and/or allergic reactions. However, with the recent formulations of intravenous iron, I think the incidence of allergic reactions has really decreased tremendously, and they really can be used very safely in our patient population. Dr. Jay Wish (07:31): Why aren't more patients with non-dialysis dependent CKD receiving effective therapies to avoid transfusion? Dr. Ellie Kelepouris (07:38): I think one of the most important observations that I've made, and really has been reported in the literature, is that anemia and chronic kidney disease are not identified early in patient populations, particularly vulnerable and at-risk populations. And that really is largely due to barriers to access to healthcare services among patients with non-dialysis dependent CKD. Social determinants of health really are key barriers, or actually promote lack of awareness, lack of ability, lack of healthcare, lack of ability for patients to receive IV iron. Racial and ethnic disparities in this minority and vulnerable population are really known to hamper the diagnosis or the ability to diagnose. And additionally, I think the most important thing is that there's lack of screening for risk factors of first degree relatives of patients with chronic kidney disease. And those vulnerable populations have limited pre-dialysis care. There's also logistical barriers to erythropoietin stimulating agents in iron therapies. They are subcutaneous, they're intravenously administered, and they are expensive medications that these patients really don't have access to. Dr. Jay Wish (09:05): So you mentioned screening, and that's obviously important part of the equation, in terms of effective anemia management. What can be done to improve screening for CKD related anemia, so that patients who are affected can be more effectively evaluated and treated? Dr. Ellie Kelepouris (09:21): Well, I think the key is really identification. All patients with chronic kidney disease should be evaluated for anemia. A hemoglobin level should really be obtained in all patients with CKD, regardless of their stage. So evaluation and basic management by CKD stage should be really guideline directed care. And the follow-up should be really carefully staged. Dr. Jay Wish (09:50): So how do the KDIGO guidelines guide our evaluation and management of treatment in patients with non-dialysis CKD? Dr. Ellie Kelepouris (10:00): Our KDIGO guidelines have published an algorithm for evaluation of anemia and basic management of chronic kidney disease. And we should start with really evaluating all patients with CKD for hemoglobin, and to identify actionable anemia, which is defined as a hemoglobin less than 10 grams per deciliter. So if you check the hemoglobin and it's above 10 or 12, then obviously they don't have anemia. However, in patients with advanced CKD, CKD stage three, four, and then finally five, I think the basic algorithm is that hemoglobin should be checked in all patients. And then, if the hemoglobin is really less than 12, or less than 13, you can proceed to an initial workup. And the initial workup is obtaining a panel, a CBC, red blood cell indices, and a white count, etc., platelets, vitamin B12, and folate levels, which is really the basic workup for anemia in the general population. (11:17): If that workup is normal, then you know you really can go ahead and treat with an ESA, if indicated, and the hemoglobin is less than 10. However, what we know is that a large percentage of those patients also have iron deficiency. So iron studies need to be obtained at the same time, and they should be treated with iron. And as we talked about, intravenous iron is really the preferred preparation, in order for anemia to be corrected. KDIGO also has taught us that we need to really screen patients for anemia in stage CKD three, at least annually. At stage CKD four, at least every six months. And at five, not on dialysis every six months, and on dialysis at least every three months. But in a dialysis unit, really in clinical practice, we measure the hemoglobin and the iron indices on a monthly basis, to make sure that patients are well treated. Dr. Jay Wish (12:23): Thanks, Ellie. For dialysis patients, they're captive, they can get the treatment that they need, they can get the screening testing that they need. But the non-dialysis CKD patients are much more elusive, if you will. So what are some of the major logistical barriers to the effective screening and treatment of our non-dialysis anemic patients? Dr. Ellie Kelepouris (12:41): I think access to care is really important. And also, the fact that these preparations that we use, the medications, the iron, the erythropoietin stimulating agents, they are really given intravenously or subcutaneously, and they come at high cost. When we try to prescribe, at least in patients who are not Medicare recipients, cost is very high, and insurance denials are very high. So access to care is really limited by insurance, in some of these patients. But although erythropoietin stimulating agents can be given subcutaneously, and patients can be taught how to administer that agent to themselves, intravenous iron needs to be delivered in an infusion center. And that really is very costly, and most likely only happens in a very small percentage of the population. So that's a really need, the logistical barriers for that patient population. Dr. Jay Wish (13:43): And since we're talking about patient populations, we know that CKD itself disproportionately affects minority populations that may have less access to healthcare. And anemia even disproportionately affects those populations as well, who may have other disorders that contribute to anemia, genetic, nutritional, etc. You want to comment about that? Dr. Ellie Kelepouris (14:04): Sure. Minority populations really are at a higher risk, and the rates of kidney failure from the biggest cause of kidney disease in our patients is diabetes. So if you look at the rates of kidney failure from diabetes by race and ethnicity, what you see is that there's a higher percentage in Black populations, Native Americans and Asian populations and Hispanics compared to Caucasians. So although these populations are at higher risk for kidney disease, they receive less medical care. And why they receive less medical care is that the percent of those patients who are at risk, only 40% of those patients are screened for risk factors. And only 24% of those patients actually have access to care with the agents that we talked about. So they really are a disenfranchised population. And the prevalence of pre-dialytic care from nephrologists in hemodialysis patients by ethnicity, is also affected, with Hispanic and non-Hispanic patients receiving poor care, compared to Caucasians. So it really is a population health issue. Dr. Jay Wish (15:26): Thanks, Ellie. So just to kind of summarize, it appears that we're not doing a very good job in identifying and treating anemia in our patients with CKD. It's actually been shown that among incident dialysis patients in the United States, the mean hemoglobin is 9.4, despite the fact that around 60% receive pre-dialysis nephrology care. That clearly indicates an unmet need for more effective anemia management strategies, both in terms of screening and intervention. (15:55): So I'd like to thank Ellie for a great discussion. I really appreciate you sharing your expertise, and I'd like to thank our audience for participating in this activity. Please join us for the remaining five podcasts in this series, Updates and Advances in Anemia of Chronic Kidney Disease. We hope you enjoy the rest of your day. Please continue on to answer the questions that follow, and complete the evaluation. 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