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Darbepoetin alfa for the management of anemia in chronic kidney disease

Allen R Nissenson, MD
Shaan Anand, MD
Section Editor
Jeffrey S Berns, MD
Deputy Editor
Alice M Sheridan, MD


Anemia, an extremely common complication of chronic kidney disease (CKD), can develop well before the onset of uremic symptoms due to end-stage renal disease (ESRD). Although anemia due to renal dysfunction generally develops when the glomerular filtration rate (GFR) declines to <30 mL/min, it can also be observed in those with markedly higher GFRs (such as 60 mL/min) [1].

If left untreated, the anemia of CKD is associated with several physiologic abnormalities, including deterioration in cardiac function and decreased cognition and mental acuity [2]. It can also be accompanied by debilitating symptoms, such as fatigue, weakness, lethargy, anorexia, and sleep disturbances. In addition, anemic patients commonly lack the stamina needed to perform normal daily activities or to work [3].

Anemia may also, in part, underlie the high cardiovascular mortality observed in the CKD population as a low hematocrit (Hct) is an independent risk factor for death in this population. In one study, for example, a 3 percent decrease in Hct was associated with a 7 percent increased risk of death [4]. This is most likely due to an increased propensity for the development of left ventricular hypertrophy (LVH) (see "Myocardial dysfunction in end-stage renal disease"). The overall result of untreated anemia in this setting is maladaptive cardiac remodeling [5], with every 1 g/dL decrease in hemoglobin (Hb) concentration being associated with a 6 percent increase in risk of LVH [6]. (See "Effects of anemia in chronic kidney disease".)

National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines recommend that patients with CKD undergo an assessment for the cause of anemia when the Hb is <13.5 g/dL in adult males and <12.0 g/dL in adult females [2]. Among patients with kidney disease, anemia arises principally because of insufficient production of erythropoietin (EPO) by the kidneys [7]. However, other causes and/or additional contributing factors may be involved, particularly iron or folate deficiency, which also require evaluation prior to treatment of the anemia [2,8]. (See "Diagnosis of iron deficiency in chronic kidney disease" and "Treatment of iron deficiency in nondialysis chronic kidney disease (CKD) patients" and "Treatment of iron deficiency in hemodialysis patients".)

The EPO deficiency evident in patients with CKD can be corrected by the exogenous administration of erythropoiesis-stimulating agents (ESAs). Two such agents are currently available in the United States (see "Treatment of anemia in nondialysis chronic kidney disease" and "Hyporesponse to erythropoiesis-stimulating agents (ESAs) in chronic kidney disease"):

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Literature review current through: Oct 2017. | This topic last updated: Aug 06, 2015.
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  1. McGonigle RJ, Wallin JD, Shadduck RK, Fisher JW. Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency. Kidney Int 1984; 25:437.
  2. KDOQI, National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis 2006; 47:S11.
  3. Delano BG. Improvements in quality of life following treatment with r-HuEPO in anemic hemodialysis patients. Am J Kidney Dis 1989; 14:14.
  4. Al-Ahmad A, Rand WM, Manjunath G, et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 2001; 38:955.
  5. Metivier F, Marchais SJ, Guerin AP, et al. Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol Dial Transplant 2000; 15 Suppl 3:14.
  6. Levin A, Singer J, Thompson CR, et al. Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Am J Kidney Dis 1996; 27:347.
  7. Caro J, Brown S, Miller O, et al. Erythropoietin levels in uremic nephric and anephric patients. J Lab Clin Med 1979; 93:449.
  8. Eschbach JW. Current concepts of anemia management in chronic renal failure: impact of NKF-DOQI. Semin Nephrol 2000; 20:320.
  9. Kleinman KS, Schweitzer SU, Perdue ST, et al. The use of recombinant human erythropoietin in the correction of anemia in predialysis patients and its effect on renal function: a double-blind, placebo-controlled trial. Am J Kidney Dis 1989; 14:486.
  10. Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. Canadian Erythropoietin Study Group. BMJ 1990; 300:573.
  11. McMahon LP, McKenna MJ, Sangkabutra T, et al. Physical performance and associated electrolyte changes after haemoglobin normalization: a comparative study in haemodialysis patients. Nephrol Dial Transplant 1999; 14:1182.
  12. Locatelli F, Olivares J, Walker R, et al. Novel erythropoiesis stimulating protein for treatment of anemia in chronic renal insufficiency. Kidney Int 2001; 60:741.
  13. Carrera F, Burnier M. Use of darbepoetin alfa in the treatment of anaemia of chronic kidney disease: clinical and pharmacoeconomic considerations. NDT Plus 2009; 2:i9.
  14. Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 2001; 16 Suppl 3:3.
  15. Nissenson AR. Novel erythropoiesis stimulating protein for managing the anemia of chronic kidney disease. Am J Kidney Dis 2001; 38:1390.
  16. Macdougall IC. Novel erythropoiesis stimulating protein. Semin Nephrol 2000; 20:375.
  17. Allon M, Kleinman K, Walczyk M, et al. The pharmacokinetics of novel erythropoiesis stimulating protein (NESP) following intravenous administration is time- and dose-linear. J Am Soc Nephrol 2000; 11:A1308.
  18. Macdougall IC, Gray SJ, Elston O, et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol 1999; 10:2392.
  19. Graf H, Lacombe J-L, Braun J, et al. Novel erythropoiesis stimulating protein (NESP) effectively maintains Hb (Hb) when administered at a reduced dose frequency compared with recombinant human erythropoietin (r-HuEPO) in ESRD patients. J Am Soc Nephrol 2000; 11:A1317.
  20. Rahman SN, Heifner KJ, Fadem SZ, et al. HRQOL improvements in anemic CKD patients treated with darbepoetin alfa (Aranesp). National Kidney Foundation Clinical Nephrology Meeting, Chicago (IL), USA, April 17–21, 2002.
  21. Nissenson AR, Swan SK, Lindberg JS, et al. Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis 2002; 40:110.
  22. Vanrenterghem Y, Bárány P, Mann JF, et al. Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients. Kidney Int 2002; 62:2167.
  23. Tolman C, Richardson D, Bartlett C, Will E. Structured conversion from thrice weekly to weekly erythropoietic regimens using a computerized decision-support system: a randomized clinical study. J Am Soc Nephrol 2005; 16:1463.
  24. Carrera F, Oliveira L, Maia P, et al. The efficacy of intravenous darbepoetin alfa administered once every 2 weeks in chronic kidney disease patients on haemodialysis. Nephrol Dial Transplant 2006; 21:2846.
  25. Mann J, Kessler M, Villa G, et al. Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients: a combined analysis of eight multicenter trials. Clin Nephrol 2007; 67:140.
  26. Carrera F, Disney A, Molina M. Extended dosing intervals with erythropoiesis-stimulating agents in chronic kidney disease: a review of clinical data. Nephrol Dial Transplant 2007; 22 Suppl 4:iv19.
  27. Aarup M, Bryndum J, Dieperink H, Joffe P. Clinical implications of converting stable haemodialysis patients from subcutaneous to intravenous administration of darbepoetin alfa. Nephrol Dial Transplant 2006; 21:1312.
  28. Jadoul M, Vanrenterghem Y, Foret M, et al. Darbepoetin alfa administered once monthly maintains haemoglobin levels in stable dialysis patients. Nephrol Dial Transplant 2004; 19:898.
  29. Ling B, Walczyk M, Agarwal A, et al. Darbepoetin alfa administered once monthly maintains hemoglobin concentrations in patients with chronic kidney disease. Clin Nephrol 2005; 63:327.
  30. Trachsler J, Glück Z, Dickenmann M, et al. Parameters for successful monthly extended dosing of darbepoetin-alpha in patients undergoing hemodialysis. Clin Nephrol 2009; 71:697.
  31. ARANESP Summary of Product Characteristics. Amgen Inc., Thousand Oaks (CA), USA, 2001.
  32. Wilhelm-Leen ER, Winkelmayer WC. Mortality risk of darbepoetin alfa versus epoetin alfa in patients with CKD: systematic review and meta-analysis. Am J Kidney Dis 2015; 66:69.
  33. Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361:2019.
  34. Macdougall IC. Antibody-mediated pure red cell aplasia (PRCA): epidemiology, immunogenicity and risks. Nephrol Dial Transplant 2005; 20 Suppl 4:iv9.
  35. Search term Aranesp www.hc-sc.gc.ca (Accessed on January 05, 2007).
  36. Jacob A, Sandhu K, Nicholas J, et al. Antibody-mediated pure red cell aplasia in a dialysis patient receiving darbepoetin alfa as the sole erythropoietic agent. Nephrol Dial Transplant 2006; 21:2963.
  37. Howman R, Kulkarni H. Antibody-mediated acquired pure red cell aplasia (PRCA) after treatment with darbepoetin. Nephrol Dial Transplant 2007; 22:1462.
  38. Lim WH, Chan D, Boudville N, et al. Patients' perceptions of subcutaneous delivery of darbepoetin alfa by autoinjector prefilled pen versus prefilled syringe: a randomized, crossover study. Clin Ther 2012; 34:1948.
  39. KDOQI, National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis 2006; 47:S11.