If you’re on dialysis, you most likely have anemia—a shortage of red blood cells. And, you probably take EPO to treat it. New studies have led to a warning by the Food and Drug Administration (FDA) about EPO. Don’t panic! Read on, and we’ll tell you what this warning means to you.
Why you need anemia treatment
Red blood cells carry oxygen to your body’s cells. Anemia starves your cells of oxygen. This causes symptoms like:
- Severe fatigue
- Muscle weakness
- Shortness of breath
- Feeling cold all the time
- Pale skin, lips, gums, and nails
- Trouble focusing your mind
These symptoms are hard to deal with. People with anemia say things like:
“Even walking from the bedroom to the kitchen I rest after every two or three steps. I stop, because I don’t have the strength to walk with. My quality of life has dropped so much that it’s almost unbearable. I can’t do anything to help my wife.”1
Some have even quit their jobs—too tired to work—then later found out anemia could be treated.
In the long run, anemia can damage your heart. When there is less oxygen in your blood, your heart speeds up. Beating faster all the time makes your heart work much harder. The muscle of the main pumping chamber can become thick and overgrown, a problem called left ventricular hypertrophy (LVH). LVH can make your heart so stiff that it can’t pump as well. This can lead to heart failure.2 It is vital for you to have your anemia treated.
How anemia is treated
In kidney failure, the main cause of anemia is a loss of erythropoietin (EPO). Kidneys sense the amount of oxygen in your blood. When levels drop, they send out EPO, a hormone that tells your bone marrow to make red blood cells. As kidneys fail, they make less EPO, so you make fewer red blood cells.
The treatment for anemia due to kidney failure is EPO. Three drugs on the market are erythrocyte (red blood cell) stimulating agents (ESAs), or cloned forms of EPO:
- Epogen® (epoetin alfa, Amgen)
- Aranesp® (darbepoetin alfa, Amgen)
- Procrit® (epoetin alfa, Ortho Biotech)
Epogen and Procrit are the same drug. Epogen is used in dialysis, while Procrit is used in predialysis. Aranesp is a new form of EPO that lasts longer. It is used for people who are predialysis or on dialysis. All three drugs are used to treat other causes of anemia as well.
Iron is also needed to treat anemia; it is the building block the body uses to form new red blood cells. Iron works best when it is given through a vein.
Anemia treatment goals in dialysis
Each month, you have a blood test for hemoglobin (Hb or Hgb). Hb picks up oxygen in your lungs and brings it to all of your cells. In healthy women, a normal Hb is 12.1 to 15.1 grams per deciliter (g/dL); in men, 13.8 to 17.2 g/dL. (“Normal” levels vary by lab.)
In people on dialysis, the Hb targets are below normal: 11 g/dL or greater in women and men. No one should be kept at a Hb of 13 g/dL or greater.3
Why are the target levels for anemia treatment less than normal? Because the Guidelines are based on research—and studies have not proven that a higher target is safe for those on dialysis.
FDA black box warnings
The FDA issues a black box warning when research suggests that a drug may cause harm in some cases. A black box warning was placed on all ESAs in March, 2007, due to new research. None of these new studies was of people on dialysis.
In people with cancer, four new studies found problems when EPO was used:
- A number of studies have linked anemia with poor outcomes in people with head and neck cancers.4,5,6,7 But in the Danish Head and Neck Cancer study, patients given EPO to reach a (normal) Hb target of 14 to 15.5 g/dL did worse than those who took a placebo.
- A study of cancer patients who were not on chemo found that EPO did not reduce the need for transfusions (the target Hb was 12 g/dL). Patients who took EPO were also more likely to die.8
- A study of whether EPO would improve quality of life in people with non-small cell lung cancer was stopped early. More people in the EPO group died than those who took a placebo. Target Hb was 12 to 14 g/dL.
- Hoffman-La Roche was testing a new ESA in people with non-small cell lung cancer (Hb target of 11 to 13 g/dL). Those who took the drug were more likely to die. The study was stopped early.
The FDA also looked at two studies in chronic kidney disease (CKD) before dialysis:
- The CHOIR study found that patients in a higher Hb group (target of 13.5 g/dL) had more adverse events like heart problems, hospital stays, or death than those in a lower Hb group (target of 11.3 g/dL).9
- The CREATE study failed to show that full correction of anemia in CKD (target of 13 to 15 g/dL) would prevent heart damage. This study used epoetin beta, a drug that is not sold in the U.S.10
EPO and quality of life
Day-to-day quality of life may affect you more than a risk of a poor outcome. Research has shown much higher quality of life when dialysis anemia is treated with EPO.11,12,13,14
In fact, a 48-72 week long Swedish study randomly assigned 416 patients (predialysis, on hemodialysis, or on peritoneal dialysis) to one of two Hb groups. One group had a target Hb of 13.5 to 16 g/dL (normal). The other group had a target Hb of 9 to 12 g/dL. This study found no higher risk of adverse events or death. The higher Hb group also had better quality of life.15
What you should do
Keep taking your EPO. The risk of anemia itself is far greater than any risk of taking the drug when it is used according to current guidelines. On the Black Box Warning, the FDA suggests using the lowest dose that will help you avoid blood transfusions. Your iron levels need to be kept in the target range so you have the building blocks you need to make red blood cells. This will allow your EPO to work.
Inflammation from an infection can also keep your body from using EPO. This is called EPO-resistance. Be sure to tell your care team about any fever, swelling, redness in your access, or other illness so it can be treated. This can help you need less EPO.
Getting more dialysis helps the red blood cells you do have to live longer. This means you may need less EPO to have a Hb in the target range. One study found less LVH and less EPO resistance in patients on short daily hemodialysis.16 A number of studies have also found that less EPO is needed for short daily17,18,19,20 or for nocturnal21,22,23,24 hemodialysis.
Talk with your doctor
EPO has been safely used to keep people on dialysis in a target Hb range of 11 to 12 g/dL for nearly 20 years— since 1989.
The Renal Physician’s Association says that you and your doctor should decide how to treat your anemia.25
You are the only one who can decide what you value more: your quality of life, or the chance of a risk. If there is a tradeoff to be made, you are the only one who can make it. Talk with your doctor and decide what will be best for you.
- Schatell D, Witten B. Anemia: Dialysis Patients’ Experiences. Nephrol News Issues. 200
- Zalunardo N, Levin A. Anemia and the heart in chronic kidney disease. Semin Nephrol. 2006 Jul;26(4):290-5
- NKF KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. (accessed 3/16/07)
- Prosnitz RG, Yao B, Farrell CL, Clough R, Brizel DM. Pretreatment anemia is correlated with the reduced effectiveness of radiation and concurrent chemotherapy in advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 2005 Mar 15;61(4):1087-95
- Stadler P, Putnik K, Kreimeyer T, Sprague LD, Koelbl O, Schafer C. Split course hyperfractionated accelerated radio-chemotherapy (SCHARC) for patients with advanced head and neck cancer: influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis. BMC Cancer. 2006 Dec 7;6:279
- Zhao KL, Liu G, Jiang GL, Wang Y, Zhong LJ, Wang Y, Yao WQ, Guo XM, Wu GD, Zhu LX, Shi XH. Association of haemoglobin level with morbidity and mortality of patients with locally advanced oesophageal carcinoma undergoing radiotherapy—a secondary analysis of three consecutive clinical phase III trials. Clin Oncol (R Coll Radiol). 2006 Oct;18(8)621-7
- van de Pol SM, Doornaert PA, de Bree R, Leemans CR, Slotman BJ, Langendijk JA. The significance of anemia in squamous cell head and neck cancer treated with surgery and postoperative radiotherapy. Oral Oncol. 2006 Feb;42(2):131-8
- “Dear Health Care Professional” letter. Not yet published.
- Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006 Nov 16;355(20):2085-98
- Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006 Nov 16;355(20):2071-84
- Delano BG. Improvements in quality of life following treatment with r-HuEPO in anemic hemodialysis patients. Am J Kidney Dis. 1989 Aug;14(2 Suppl):14-8
- Stevens JM, Auer J, Strong CA, Hughes RT, Oliver DO, Winearis CG, Cotes PM. Stepwise correction of anaemia by subcutaneous administration of human recombinant erythropoietin in patients with chronic renal failure maintained by continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant. 1991;6(7):487-94
- Levin NW, Lazarus JM, Nissenson AR. National Cooperative rHu Erythropoietin Study in patients with chronic renal failure—an interim report. Am J Kidney Dis. 1993 Aug;22(2 Suppl 1):3-12
- Glaspy J. Phase III clinical trials with darbepoetin: implications for clinicians. Best Pract Res Clin Haematol. 2005;18(3):407-16
- Furuland H, Linde T, Ahlmen J, Christensson A, Strombom U, Danielson BG. A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrol Dial Transplant. 2003 Feb;18(2):353-61
- Ayus JC, Mizani MR, Achinger SG, Thadhani R, Go AS, Lee S. Effects of short daily versus conventional hemodialysis on left ventricular hypertrophy and inflammatory markers: a prospective, controlled study. J Am Soc Nephrol. 2005 Sep;16(9):2778-88
- Ting GO, Kjellstrand C, Freitas T, Carrie BJ, Zarhamee S. Long-term study of high-comorobidity ESRD patients converted from conventional to short daily hemodialysis. Am J Kidney Dis. 2003 Nov;42(5):1020-35
- Koshikawa S, Akizawa T, Saito A, Kurokawa K. Clinical effect of short daily in-center hemodialysis. Nephron Clin Pract. 2003;95(1):c23-30
- Ettari G, Boccardo G, De Prisco O, Maurino D. [Daily short dialysis. First results in a group of patients in home dialysis training] article in Italian. Minerva Urol Nefrol. 2002 Jun;54(2):139-43
- Vos PF, Zilch O, Kooistra MP. Clinical outcome of daily dialysis. Am J Kidney Dis. 2001 Jan;37(1 Suppl 2):S99-S102
- Klarenbach S, Heidenheim AP, Leitch R, Lindsay RM. Reduced requirement for erythropoietin with quotidian hemodialysis therapy. ASAIO J. 2002 Jan-Feb;48(1):57-61
- Agar JW, Knight RJ, Simmonds RE, Boddington JM, Waldron CM, Somerville CA. Nocturnal haemodialysis: an Australian cost comparison with conventional satellite haemodialysis. Nephrology (Carlton). 2005 Dec;10(6):557-70
- Yuen D, Richardson RM, Fenton SS, McGrath-Chong ME, Chan CT. Quotidian nocturnal hemodialysis improves cytokine profile and enhances erythropoietin responsiveness. ASAIO J. 2005 May-Jun;51(3):236-41
- Schwartz DI, Pierratos A, Richardson RM, Fenton SS, Chan CT. Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease. Clin Nephrol. 2005 Mar;63(3):202-8
- RPA Guidance to Nephrology Care Providers Regarding the FDA Public Health Advisory on ESAs. (accessed 3/18/07)