The standard of care and standard therapeutic options available for a patient with anemia in CKD are examined.
Peter L. Salgo, MD: We’ve been talking around all of this in terms of therapeutic options and transfusions, and I know we’re going to get down in the weeds on this in a little bit. This might be a good time to back off, take a 10,000-foot view, and review our options. What are the standard therapeutic options for the anemia of chronic kidney disease [CKD]? I heard iron; you might as well start with that.
Robert Provenzano, MD, FACP, FASN: To [address] Dan’s point, there are certain basic demographic issues. What stage of CKD becomes important in the work-up? For the average patient with CKD who has anemia, there are several things you need to do. You need a CBC [complete blood count]; you need to know that iron is present. That would be the absolute baseline. Based on that, in chronic kidney disease, which to Dan’s point is an inflammatory state, if iron stores are adequate, then the decision regarding whether to treat needs to be made. If they’re iron deficient, they need iron replacement, in which case you would start looking for a reason for iron deficiency. Dan?
Daniel W. Coyne, MD: Yeah. Our treatment options are oral iron, and there are a number of products available. There is 1 type of oral iron called Auryxia [ferric citrate], which can be given in high doses if they take it with meals. The reason I bring this up is this: if they take it over a 3- to 6-month course, it is equivalent to giving them IV [intravenous] iron of a substantial amount. Right now, it’s priced very expensively, so that’s a second option. The third option is to give them various forms of IV iron, generally to a total dose of about 1,000 milligrams infused. That can treat iron deficiency, and it helps the anemia quite a bit. After that, ESAs [erythropoietin-stimulating agents]: epoetin and darbepoetin are the major ones.
Peter L. Salgo, MD: Yeah, we’ll get to that. Before we leave iron, the reputation for iron has always been its tolerability—oral iron. It’s also constipating: a lot of patients just hate it.
Daniel W. Coyne, MD: Yes.
Peter L. Salgo, MD: I can tell you in my household, one of my family members was severely anemic postoperatively and would not take it. Is that your experience with it?
Daniel W. Coyne, MD: There is a lot of variability. The classic model is to tell them to take a pill 3 times a day, and I never tell them that. I tell them to try and take it once a day, and if we can keep you on it for 4 months, then there’s a good chance it may help. Many insurers require us to demonstrate that they’ve either failed oral iron or cannot tolerate it. Our guidelines also recommend oral iron as the first choice because in randomized trials, it’s about as good as getting a moderately high dose of IV iron, so why not give it orally? You avoid the IV cost and the risk of IV medications. It’s a reasonable first option, and it’s cheap.
Robert Provenzano, MD, FACP, FASN: I want to build on this because these patients are complex. To [address] Dan’s point on the diet, our patients are usually on a restricted diet by the time they’re anemic.
Peter L. Salgo, MD: Right.
Robert Provenzano, MD, FACP, FASN: Second, I am a big proponent of minimizing the pill burden. Our patients are on a huge number of medications; they see multiple physicians. A wise practitioner looks carefully at the medications and the interactions and the cost, for that matter. I agree with Dan; a trial of iron is reasonable, but I have not been as lucky with its outcomes as he may have been.
Peter L. Salgo, MD: From an insurance perspective, iron is cheap, right?
Stanley Crittenden, MD: Iron is cheap, and Dan is correct: most payers will typically require some form of oral trial. If a patient can’t tolerate it, then that can be clearly documented in the medical record, and then you advance to the next step, which is some form of IV iron.
Peter L. Salgo, MD: You used the word step. Is that the insurance company’s phrase for stepwise, will escalate?
Stanley Crittenden, MD: Step therapy, correct.
Peter L. Salgo, MD: Yes, I thought I was going to hear it eventually. Is that necessarily a bad thing, for the insurance companies to want to do some sort of step therapy here, guys?
Daniel W. Coyne, MD: Our guidelines say that should be the first therapy, so I don’t think it’s inappropriate. There are not many cases where I object: it’s when the anemia is severe, and I’m very confident they’ll respond to iron, and I want to give an IV to speed up the response rate and not take a chance that I’ve wasted 2 months on them not responding.
Peter L. Salgo, MD: If I hear you correctly, you’d start iron, but you’d monitor this, and if they’re not responding, then you’d move on.
Daniel W. Coyne, MD: Yeah. If you can say, “Look, they’re bad,” I have not had trouble with insurers turning us down when we want IV iron if we’ve made rational decisions along the way. Sometimes, we’ve given oral iron, and sometimes we’ve said, “Look, it’s bad, and we need this to go up fast, so we want to give them IV iron, or I’ll pull out epoetin.” Then I threaten them with the cost of epoetin, and then all of a sudden, they’re way more interested in giving IV iron. It’s a win-win in my view.
Peter L. Salgo, MD: I said we would come back to it, so I’m going to keep my promise. You did mention getting off iron. For whatever reason, you want to move on to erythropoietin-stimulating agent therapy, and I’m assuming the reason you want to move on is that the iron isn’t working well. What would be the indication to move on from a clinical perspective?
Daniel W. Coyne, MD: The hemoglobin is too low in the opinion of the nephrologist, which for pretty healthy people is a hemoglobin level persistently in the 9s. I usually say, “Look, if it’s going on for the 3 months, then they’re going to stay there, and now is the time to pull it out.” In my elderly patients with disabilities, I may wait until they’re persistently in the 8s to deal with the expense of epoetin, recognizing that it’s changing the hemoglobin, but it’s not changing their cardiovascular outcomes, and it’s probably not going to make them feel better.
Peter L. Salgo, MD: Stan, what are your guidelines? What do you do in your practice?
Stanley Crittenden, MD: In my personal practice, since I practice as well, I agree with Dan here. I do the same thing. From a population standpoint though, we try to toe the line with the KDIGO [Kidney Disease: Improving Global Outcomes] guidelines, which as Dan indicated requires some form of oral iron. We then tend to watch KDIGO’s recommendations in terms of hemoglobin, so we don’t start people above 10g/dL. If you’re asking for an ESA, for example, in a patient above 10g/dL, that’s not indicated based on guidelines, so something like that would be probably not allowed. Similarly, we’re sticking with the guidelines as we see them in terms of strict evidence.
Peter L. Salgo, MD: Yeah. The guidelines that I’ve seen, it’s KDIGO, right? I’m not a nephrologist, but I listen carefully to you guys. The guidelines read like they’re written by committee; not that they’re bad, but they read as though they’re carefully parsed. Here’s a quote: “You’re going to balance the potential benefits of transfusion reduction and anemia-related symptoms against the risks of harm.” Well, OK, but reading that doesn’t tell me very much.
Robert Provenzano, MD, FACP, FASN: First of all, I agree with everything Dan and Stanley said, but as a physician, this is what we know. There’s population health in which we make some high-level decisions, and then there’s an individual sitting across an examination table from you for whom you make a 1-on-1 decision. For example, if I have an elderly patient with a hemoglobin level of 8.5g/dL who now has recent acute cognitive dysfunction, I’m going to treat the anemia, right?
Peter L. Salgo, MD: Right.
Robert Provenzano, MD, FACP, FASN: We need to be careful. Population health is important, but then you have to take that information and apply it to an individual.
Peter L. Salgo, MD: That’s where I was going. Your person, your patient, is an N of 1, whereas an insurance company, and I don’t mean this in a negative way, has got to make plans in terms of population dynamics. You’ve got somebody sitting across from you who says, “I don’t feel well and my hemoglobin is 9g/dL,” so what are we going to do about this?
Robert Provenzano, MD, FACP, FASN: I would just add, because Stanley is right on point. Physicians must advocate for their patients, and they always have. The difference is that, in the 21st century, our advocacy is translated into a lot of paperwork to get approvals, which is time consuming. That is the conundrum we’re in.
Daniel W. Coyne, MD: When we see a patient, and we’re talking about using ESAs, the factor that I look at, other than the hemoglobin, is their cardiovascular history. We know these classes of drugs, at least when they were targeting a normal hemoglobin level in the TREAT trial versus placebo, doubled the risk of stroke, and if you had a prior stroke, it about tripled your risk. I joke that there are 2 types of patients to whom I offer ESAs: those who agree and have never read the package insert and those who have read the package insert and never agree.
The second thing is cancer risk. If they’ve had a prior cancer or have an active cancer, it’s probably contraindicated depending on the various issues to be using these products. You have to have risk-benefit shifts greatly against using these drugs. The truth is that we make those decisions all the time. I’ve never had a prescription for an ESA turned down by an insurer, but there are many times where I’m sure the insurer would have approved it, and I don’t think it’s good, and the patient is certainly not going to take it.