Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Hypertension following erythropoietin (EPO) in chronic kidney disease

INTRODUCTION

Hypertension is a common adverse effect of erythropoietin (EPO) treatment that is observed among patients with chronic kidney disease (CKD) and even among healthy subjects who receive erythropoietin [1-3].

This topic reviews hypertension related to erythropoietin among CKD patients. Other issues related to erythropoietin among CKD patients, including hemoglobin (Hb) targets, are addressed elsewhere. (See "Erythropoietin for the anemia of chronic kidney disease among predialysis and peritoneal dialysis patients" and "Erythropoietin for the anemia of chronic kidney disease in hemodialysis patients" and "Anemia of chronic kidney disease: Target hemoglobin/hematocrit for patients treated with erythropoietic agents".)

EPIDEMIOLOGY AND RISK FACTORS

Approximately 20 to 30 percent of patients who receive erythropoietin intravenously for the anemia of CKD develop an elevation in diastolic pressure of 10 mmHg or more [4,5]. Much of the evidence that erythropoietin contributes to hypertension in CKD patients is from a series of meta-analyses [5,6]. As an example, in one meta-analysis that included six randomized trials comparing erythropoietin versus placebo or no erythropoietin (n = 387 patients), patients who did not receive erythropoietin had a lower risk of hypertension (relative risk [RR] 0.50, 95% CI 0.33-0.76).

Another meta-analysis from the Cochrane Collaboration that included four controlled trials in nondialysis CKD patients showed a 26 percent higher risk of hypertension in erythropoietin-treated patients, compared with no erythropoietin or placebo, but the effect was not statistically significant [7].

Putative risk factors for erythropoiesis-stimulating agent (ESA)-associated hypertension include the following:

      

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2014. | This topic last updated: Sep 11, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Lundby C, Thomsen JJ, Boushel R, et al. Erythropoietin treatment elevates haemoglobin concentration by increasing red cell volume and depressing plasma volume. J Physiol 2007; 578:309.
  2. Berglund B, Ekblom B. Effect of recombinant human erythropoietin treatment on blood pressure and some haematological parameters in healthy men. J Intern Med 1991; 229:125.
  3. Lundby C, Olsen NV. Effects of recombinant human erythropoietin in normal humans. J Physiol 2011; 589:1265.
  4. Smith KJ, Bleyer AJ, Little WC, Sane DC. The cardiovascular effects of erythropoietin. Cardiovasc Res 2003; 59:538.
  5. Strippoli GF, Craig JC, Manno C, Schena FP. Hemoglobin targets for the anemia of chronic kidney disease: a meta-analysis of randomized, controlled trials. J Am Soc Nephrol 2004; 15:3154.
  6. Krapf R, Hulter HN. Arterial hypertension induced by erythropoietin and erythropoiesis-stimulating agents (ESA). Clin J Am Soc Nephrol 2009; 4:470.
  7. Cody J, Daly C, Campbell M, et al. Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients. Cochrane Database Syst Rev 2005; :CD003266.
  8. Watson AJ, Gimenez LF, Cotton S, et al. Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin. Am J Med 1990; 89:432.
  9. Nissenson AR, Korbet S, Faber M, et al. Multicenter trial of erythropoietin in patients on peritoneal dialysis. J Am Soc Nephrol 1995; 5:1517.
  10. Neeman T, Mats V. FDA statistical review. HFM-570, BLA 97–0006. EPO label extension for pediatric hemodialysis patients. May 23, 1997. www.fda.gov.
  11. Ishimitsu T, Tsukada H, Ogawa Y, et al. Genetic predisposition to hypertension facilitates blood pressure elevation in hemodialysis patients treated with erythropoietin. Am J Med 1993; 94:401.
  12. Drüeke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355:2071.
  13. Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007; 369:381.
  14. Palmer SC, Navaneethan SD, Craig JC, et al. Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med 2010; 153:23.
  15. Koulouridis I, Alfayez M, Trikalinos TA, et al. Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis. Am J Kidney Dis 2013; 61:44.
  16. Caravaca F, Pizarro JL, Arrobas M, et al. Antiplatelet therapy and development of hypertension induced by recombinant human erythropoietin in uremic patients. Kidney Int 1994; 45:845.
  17. Vaziri ND. Mechanism of erythropoietin-induced hypertension. Am J Kidney Dis 1999; 33:821.
  18. Heidenreich S, Rahn KH, Zidek W. Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. Kidney Int 1991; 39:259.
  19. Hand MF, Haynes WG, Johnstone HA, et al. Erythropoietin enhances vascular responsiveness to norepinephrine in renal failure. Kidney Int 1995; 48:806.
  20. Eschbach JW, Abdulhadi MH, Browne JK, et al. Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial. Ann Intern Med 1989; 111:992.
  21. Raine AE, Roger SD. Effects of erythropoietin on blood pressure. Am J Kidney Dis 1991; 18:76.
  22. Marrero MB, Venema RC, Ma H, et al. Erythropoietin receptor-operated Ca2+ channels: activation by phospholipase C-gamma 1. Kidney Int 1998; 53:1259.
  23. Brochu E, Lacasse S, Larivière R, et al. Differential effects of endothelin-1 antagonists on erythropoietin-induced hypertension in renal failure. J Am Soc Nephrol 1999; 10:1440.
  24. Miyashita K, Tojo A, Kimura K, et al. Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients. Hypertens Res 2004; 27:79.
  25. Lerche D, Schmidt R, Zoellner K, et al. Rheology in whole blood and in red blood cells under recombinant human erythropoietin therapy. Contrib Nephrol 1989; 76:299.
  26. Anastassiades E, Howarth D, Howarth J, et al. Influence of blood volume on the blood pressure of predialysis and peritoneal dialysis patients treated with erythropoietin. Nephrol Dial Transplant 1993; 8:621.
  27. Vaziri ND. Anemia and anemia correction: surrogate markers or causes of morbidity in chronic kidney disease? Nat Clin Pract Nephrol 2008; 4:436.
  28. Abiose AK, Aronow WS, Moreno H Jr, et al. Increased vascular alpha1-adrenergic sensitivity in patients with renal failure: receiving recombinant erythropoeitin. Am J Ther 2007; 14:427.
  29. Briet M, Barhoumi T, Mian MO, et al. Effects of recombinant human erythropoietin on resistance artery endothelial function in stage 4 chronic kidney disease. J Am Heart Assoc 2013; 2:e000128.
  30. Martinez-Vea A, Bardají A, García C, et al. Long-term myocardial effects of correction of anemia with recombinant human erythropoietin in aged patients on hemodialysis. Am J Kidney Dis 1992; 19:353.
  31. Novak BL, Force RW, Mumford BT, Solbrig RM. Erythropoietin-induced hypertensive urgency in a patient with chronic renal insufficiency: case report and review of the literature. Pharmacotherapy 2003; 23:265.
  32. Onoyama K, Hori K, Osato S, Fujishima M. Haemodynamic effect of recombinant human erythropoietin on hypotensive haemodialysis patients. Nephrol Dial Transplant 1991; 6:562.
  33. Edmunds ME, Walls J, Tucker B, et al. Seizures in haemodialysis patients treated with recombinant human erythropoietin. Nephrol Dial Transplant 1989; 4:1065.
  34. Kaupke CJ, Kim S, Vaziri ND. Effect of erythrocyte mass on arterial blood pressure in dialysis patients receiving maintenance erythropoietin therapy. J Am Soc Nephrol 1994; 4:1874.