VIDEO: Treating anemia in cases of severe CKD

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Well, for patients who are on dialysis, there's many reasons why they get anemic. Obviously, the end stage of their kidney disease, the decreased number of erythropoietin-producing cells, greater issues with regards to dysfunction of oxygen sensing, as well as the inflammatory state of the CKD and the dialysis, the dialysis itself may be an inflammatory stimulus because of the exposure of the blood to the artificial membranes, the tubing, et cetera. And then there's ongoing blood loss in the dialysis circuit, phlebotomy, vascular access procedures, et cetera. So the multifactorial nature of anemia in patients who are on dialysis produces, as I said, over 90% of the patients have one or more of those reasons for being anemic, and that's why it's so prevalent.

So the mainstays of therapy in that population are iron supplementation, intravenous iron given regularly on dialysis. And with dialysis patients, we do have the advantage of having them, so to speak, captive, especially if they're in-center hemodialysis patients. We measure their CBCs and their iron levels, et cetera, on a regular basis. And if they need parenteral therapy, either iron or an ESA, it's very easy to administer it through the dialysis circuit so that it's basically invisible to the patient. However, again, we have subsets of patients that don't respond adequately to conventional therapy. They remain anemic with hemoglobins less than 10, despite what we would consider to be generous doses of ESAs and iron. And this is the subset of patients that we call ESA-hyporesponsive. And it's estimated that this is anywhere between 15% and 20% of dialysis patients at any given time. And they're not necessarily the same patients months after month. Patients go in and out of this category, depending upon intercurrent illnesses, hospitalizations, inflammatory states, et cetera. But any given month, you probably will find about 15% to 20% of patients who meet the definition of ESA hyporesponsiveness, either they're on a very high dose of ESA to achieve the target hemoglobin level, or they don't achieve the target hemoglobin level.

So there are other options that have now been approved by the FDA. One of these is one of these HIF-pro hydroxylase inhibitors. The name is daprodustat (Jesduvroq; GlaxoSmithKline). It has been approved by the FDA, and probably will be marketed to the various dialysis providers sometime in the next several months and will be available for use in, what I would see would be three populations that would be most suitable. One would be those patients who are ESA hyporesponsive, in whom the effects of the HIF-pro hydroxylase on benefiting iron metabolism may prove to overcome the ESA resistance. Home dialysis patients, who have to come to a dialysis center, home dialysis unit, to get their ESA injections might favor these agents, which would also decrease their need for intravenous iron, so decreasing the trips to the dialysis provider for parenteral ESA therapy, iron infusions, et cetera. They may prefer an oral agent like a HIF-PHI.

And there are some data from some of the clinical trials that suggest that you may see more stability in the hemoglobin with the HIF-PHIs than you do with ESAs. Again, probably because it blunts the effect of inflammation on ESA hyporesponsiveness. So again, patients who have these large swings in their hemoglobin, even though they may be EPO responsive part of the year, if they're EPO responsive another part of the year, may not be today, but it might be next month, or the month after, those may be an appropriate candidate for alternative therapy with the HIF-PHIs. If it ain't broke, I wouldn't fix it. For the 80 plus percent of patients who are doing fine on ESAs, reasonable, modest dose, achieve their target hemoglobin levels, I don't suggest that we need to change that. But I think for patients who, for whatever reason, are not responding to ESAs well, or have more of a, shall we say logistical burden in getting their ESAs and their IV iron because they're at home, and of course we're trying to encourage more home dialysis, then those would be reasonable candidates to consider alternative therapies.