Anemia in Kidney Disease: To Treat or Not to Treat… and if so, how much?

In a recent AJKD article, Dr. Wong and colleagues recently shed new light on the anemia debate in hospitalized hemodialysis patients. Using retrospective data from the Southern Alberta Renal Program (SARP), Calgary Health Region, the authors studied 700 hospitalizations in 484 patients to determine the impact of increasing the dose of erythropoiesis-stimulating agents (ESAs) on outcomes such as need for blood transfusion and the risk of cardiovascular events and death. The authors further examined the percentage of patients who subsequently exceeded recommended hemoglobin targets within 90 days of hospitalization. Dr. Robert Quinn (RQ), the study’s corresponding author, discussed the findings of the study with eAJKD Contributor Jane Schell (eAJKD).

eAJKD: There have been many studies assessing ESA dosing and outcomes. What led you to study erythropoietin in hospitalized patients?

RQ: It is a common clinical entity we encounter on a daily basis. There has been a lot written on how to manage the outpatient anemic patient with CKD and ESRD. As I was rounding in the hospital with one of the fellows, we realized there was not a lot of literature to help guide management of hospitalized patients with chronic kidney disease. There’s a real variability in practice, so we decided to design a study to generate some hypotheses that we might test in randomize trials in the future.

eAJKD: Can you discuss the major findings of the study?

RQ: We were interested in determining whether increasing the dose of ESA is associated with important outcomes such as need for blood transfusion and risk for cardiovascular disease. We found that an increased dose of ESA was not associated with reduced need for blood transfusion, risk of cardiovascular events, or death. We did however find that increasing erythropoietin dose by greater than 40 micrograms per week was associated with an increased risk of exceeding the hemoglobin target.

eAJKD: How do you interpret these results, and how will these results impact clinical practice?

RQ: What we found was that one is more likely to exceed a recommended target when increasing ESA dose during hospitalization, and there doesn’t seem to be any upside in terms of other outcomes, like avoiding transfusions. For me, personally, this gives me a bit of caution in ramping up the dose of ESAs in hospitalized patients. Ultimately, we really need a randomized trial to address the limitations of this study before I can recommend one way over the other.

eAJKD: Were you surprised that the increased dose was not associated with reduced risk of transfusion?

RQ: We were slightly surprised by that finding. But by the same token, one of the other driving factors for doing this study was the fact that the hospitalized patients are often very resistant to increasing ESA doses because of the illnesses.

eAJKD: The results demonstrated that at higher EPO doses, there was a trend for higher risk of transfusion after you adjusted for baseline characteristics. Can you elaborate on this finding, especially with regards to the concept of EPO resistance?

RQ: Keep in mind that this is not a randomized controlled trial. In our study, there were patients who were treated with the highest does of EPO who were also likely bleeding. For example, in a patient whose hemoglobin was down trending from bleeding, one may be more inclined to increase the ESA dose during rounds. Those would be the patients that would not only be at highest risk for transfusion, they’re also the ones receiving the highest dose of the ESA. This situation could confound one’s results and may explain why we saw those findings.

eAJKD: The study excluded patients who were hospitalized within six months. This was a fairly large group, 475 patients. How would the findings have changed had they been included in the analysis?

RQ: The reason we excluded those patients was we wanted to get the cleanest cohort to study, and avoiding the people who are repeatedly hospitalized and never really get back to a stable situation as an outpatient. But a lot of the hospitalizations are in patients who have been hospitalized within the last six months. I don’t know how the findings would compare if we had included the 475 patients. At this point, it would be only speculative.

eAJKD: The Alberta Kidney Disease Network has become a powerful contributor to the nephrology literature. Can you share more about the clinical goals and philosophy of the network?

RQ: The network has a great collaboration of investigators with diverse skill sets. With good mentors to support junior faculty, this network can be very supportive for one’s career. One’s work is certainly stronger when one is in an environment like this network.

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