When using erythropoiesis-stimulating agents (ESAs) to correct anemia in patients with chronic kidney disease, focus less on hitting a given hemoglobin target and more on improving patient-perceived quality of life in such areas as fatigue, weakness, and shortness of breath, advises Alan S. Kliger, MD, Chief Medical Officer and Chief Quality Officer for the Saint Raphael Healthcare System in New Haven, Conn.
In an editorial published in the February issue of the Clinical Journal of the American Society of Nephrology (2012;7:354-357), you and your colleagues contend that patients and their physicians should tailor the use of ESAs within the context of the patient’s perceived quality of life. What experiences in your practice brought you to this conclusion?
Dr. Kliger: Several studies of patients with CKD and those on dialysis have shown the dangers of treating anemia of CKD to goal hemoglobin (Hb) of 13 g/dL or higher. For decades, we have prescribed ESAs to achieve goal Hb levels, as if the Hb level itself is the important outcome.
However, our patients tell us a different story. For some, the Hb level appears to make no difference to their health, as long as they do not have profound anemia. For others, symptoms develop and change lives at different Hb levels. Since each of our patients is different, a single goal Hb level does not work, particularly when we know that there is potential harm to set goal Hb at 13 or higher, and we do not know if that harm extends to goals below 13.
Do you endorse this practice for any specific subgroup of patients—for example, the sickest patients who are more likely to succumb to ESRD than to the cardiovascular side effects of ESAs—or would you like to see it applied across the spectrum of all CKD patients with anemia?
Dr. Kliger: I believe the practice of individualizing anemia treatment should be done for all patients. For each patient, we must consider the balance between the benefits and the risks of ESA treatment. That balance will not be the same for all.
For example, a minority of patients with ischemic heart disease develop increased angina and other symptoms when they become more anemic. For these patients, the benefits of ESAs, iron, or blood transfusions likely outweigh the risks, even if their achieved Hb levels to eliminate angina are in the range of 13 g/dL. For other patients, anemia appears to have no effect on their health, even when Hb levels are below 10 g/dL. For these patients, the risks of treating anemia outweigh the benefits, and ESAs should not be used.
What is your opinion of the FDA recommendations for more conservative dosing of ESAs in patients with CKD? To accommodate the FDA, ESA labels now recommend that physicians consider starting ESA treatment when Hb level is less than 10 g/dL, without defining how far below 10 g/dL is appropriate for initiation and without recommending a goal of 10 g/dL or higher.
Dr. Kliger: Since several studies in recent years have been published showing the increased incidence of complications—some life-threatening—associated with using ESAs to goal Hb at 13 g/dL or higher, the FDA has responded appropriately to change the label for ESA use to reflect these dangers. The challenge is that there are no studies that show what the danger is when Hb goals are less than 13 g/dL. Is it safe to set goal Hb at 10 or 9 g/dL or higher? We do not know.
If a single goal Hb level is not appropriate for all patients, I think it is wiser to craft individualized therapy rather than seeking to find the single goal best for all. This does mean that each patient and his or her doctor must consider the relative risks and benefits of treatment to the best of their ability, and not simply depend on the FDA “black box” warning to prescribe a dose of ESA.