Erythropoietin in the critically ill: do we ask the right questions?

Critical Care

Volumn 16, Issue 5, 2012, Pages

  McCook, Oscar ^a   Georgieff, Michael ^a   Scheuerle, Angelika ^a   Möller, Peter ^a   Thiemermann, Christoph ^b   Radermacher, Peter ^a  

^a UNIVERSITY HOSPITAL ULM   (Germany)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PLACEBO; RECOMBINANT ERYTHROPOIETIN; ERYTHROPOIETIN; RECOMBINANT PROTEIN;

ANEMIA; ARTICLE; CHRONIC KIDNEY DISEASE; COMORBIDITY; CRITICALLY ILL PATIENT; DRUG EFFICACY; DRUG TOLERABILITY; HEART MUSCLE ISCHEMIA; MORBIDITY; MORTALITY; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REPERFUSION INJURY; ACUTE KIDNEY INJURY; ANIMAL; ANIMAL MODEL; CHRONIC KIDNEY FAILURE; CLINICAL TRIAL (TOPIC); COMPLICATION; CRITICAL ILLNESS; DRUG RESISTANCE; HUMAN;

ACUTE KIDNEY INJURY; ANIMALS; CLINICAL TRIALS AS TOPIC; CRITICAL ILLNESS; DRUG RESISTANCE; ERYTHROPOIETIN; HUMANS; MODELS, ANIMAL; RECOMBINANT PROTEINS; RENAL INSUFFICIENCY, CHRONIC; REPERFUSION INJURY;

EID: 84866776009     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/cc11430     Document Type: Article

References (68)

1. Moore E, Bellomo R. Erythropoietin (EPO) in acute kidney injury. Ann Intensive Care 2011, 1:3. 10.1186/2110-5820-1-3, 3159901, 21906325.
2. Patel NS, Collino M, Yaqoob MM. Erythropoietin in the intensive care unit: beyond treatment of anemia. Ann Intensive Care 2011, 1:40. 10.1186/2110-5820-1-40, 3224459, 21943500.
3. Patel NSA, Nandra KK, Thiemermann C. Bench-to-bedside review: Erythropoietin and its derivatives as therapies in critical care. Crit Care 2012, 16:229. 10.1186/cc11315, 22839413.
4. Ghezzi P, Bernaudin M, Bianchi R, Blomgren K, Brines M, Campana W, Cavaletti G, Cerami A, Chopp M, Coleman T, Digicaylioglu M, Ehrenreich H, Erbayraktar S, Erbayraktar Z, Gassmann M, Genc S, Gokmen N, Grasso G, Juul S, Lipton SA, Hand CC, Latini R, Lauria G, Leist M, Newton SS, Petit E, Probert L, Sfacteria A, Siren AL, Talan M, et al. Erythropoietin: not just about erythropoiesis. Lancet 2010, 375:210. 10.1016/S0140-6736(09)61924-3, 20060161.
5. Goldsmith D. Extraordinary popular delusions and the madness of crowds: puncturing the epoietin bubble - lessons for the future. Nephrol Dial Transplant 2011, 26:24-28. 10.1093/ndt/gfq577, 20852072.
6. Bamgbolla OF. Patterns of resistance to erythropoietin-stimulating agents in chronic kidney disease. Kidney Int 2011, 80:464-474. 10.1038/ki.2011.179, 21697809.
7. De Beuf M, Verhulst A, Helbert M. Tubular erythropoietin receptor expression mediates erythropoietin-induced renoprotection. Open Hematol J 2009, 3:1-10.
8. Elliott S, Busse L, Swift S, McCaffery I, Rossi J, Kassner P, Begley CG. Lack of expression and function of erythropoietin receptors in the kidney. Nephrol Dial Transplant 2011, 27:2733-2745.
9. Saqib M, Duling L, Krier K, Howdieshell TR. Temporal and spatial expression of erythropoietin, erythropoietin receptor and common β receptor in wound fluid and granulation tissue. Wounds 2009, 21:164-171.
10. Li Z, Hui T, Xun M, Duan C, Zhang Y, Yin Y, Din Y, Zhang L. Expression of erythropoietin and erythropoietin receptor on renal tissue in children with acute kidney injury (abstract). Pediatr Res 2011, 70:765.
11. McCook O, Simon F, Matějková S, Matallo J, Scheuerle A, Moeller P, Georgieff M, Calzia E, Radermacher P, Schelzig H. Reduced EPO receptor expression may contribute to limited pleitropic effects of EPO during critical illness. Critical Care 2012, 16(Suppl 1):P440.
12. Gorio A, Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, Cichetti C, Di Giulio AM, Vardar E, Cerami A, Brines M. Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci USA 2002, 99:9450-9455. 10.1073/pnas.142287899, 123161, 12082184.
13. Su KH, Shyue SK, Kou YR, Ching LC, Chiang AN, Yu YB, Chen CY, Pan CC, Lee TS. β Common receptor integrates the erythropoietin signaling in activation of endothelial nitric oxide synthase. J Cell Physiol 2011, 226:3330-3339. 10.1002/jcp.22678, 21321940.
14. Urao N, Okigaki M, Yamada H, Aadachi Y, Matsuno K, Matsui A, Matsunaga S, Tateishi K, Nomura T, Takahashi T, Tatsumi T, Matsubara H. Erythropoietinmobilized endothelial progenitors enhance reendothelialization via Aktendothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res 2006, 98:1405-1413. 10.1161/01.RES.0000224117.59417.f3, 16645141.
15. Leist M, Ghezzi P, Grasso G, Bianchi R, Villa P, Fratelli M, Savino C, Bianchi M, Nielsen J, Gerwien J, Kallunki P, Larsen AK, Helboe L, Christensen S, Pedersen LO, Nielsen M, Torup L, Sager T, Sfacteria A, Erbayraktar S, Erbayraktar Z, Gokmen N, Yilmaz O, Cerami-Hand C, Xie QW, Coleman T, Cerami A, Brines M. Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 2004, 305:239-242. 10.1126/science.1098313, 15247477.
16. Nijboer W, Ottens P, van Dijk A, van Goor H, Ploeg RJ, Leuvenink HG. Donor pretreatment with carbamylated erythropoietin in a brain death model reduces inflammation more effectively than erythropoietin while preserving renal function. Crit Care Med 2010, 38:1156-1161.
17. Simon F Scheuerle A, Gröger M, Vcelar B, McCook O, Möller P, Georgieff M, Calzia E, Radermacher P, Schelzig H. Comparison of carbamylated fusion and recombinant human erythropoietin during porcine aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury. Intensive Care Med 2011, 37:1525-1533. 10.1007/s00134-011-2303-4, 21779851.
18. Wang Y, Zhang ZG, Rhodes K, Renzi M, Zhang RL, Kapke A, Lu M, Pool C, Heavner G, Chopp M. Post-ischemic treatment with erythropoietin or carbamylated erythropoietin reduces and improves neurological outcome in a rat model of focal cerebral ischemia. Br J Pharmacol 2007, 151:1377-1384. 2189829, 17603558.
19. Yuen CM, Leu S, Lee FY, Yen CH, Lin YC, Chua S, Chung SY, Chai HT, Sheu JJ, Ko SF, Sun CK, Yip HK. Erythropoietin markedly attenuates brain infarct size and improves neurological function in the rat. J Invest Med 2010, 58:893-904.
20. van der Meer P, Lipsic E, Henning RH, Boddeus K, van der Velden J, Voors AA, van Veldhuisen DJ, van Gilst WH, Schoemaker RG. Erythropoietin induces neovascularization and improves cardiac function in rats with heart failure after myocardial infarction. J Am Coll Cardiol 2005, 46:125-133. 10.1016/j.jacc.2005.03.044, 15992646.
21. Burger DE, Xiang FL, Hammoud L, Jones DL, Feng Q. Erythropoietin protects the heart from ventricular arrhythmia during ischemia and reperfusion via neuronal nitric-oxide synthase. J Pharmac Exp Ther 2009, 329:900-907.
22. Sharples EJ, Patel N, Brown P, Stewart K, Mota-Philipe H, Sheaff M, Kieswich J, Allen D, Harwood S, Raftery M, Thiemermann C, Yaqoob MM. Erythropoietin protects the kidney against injury and dysfunction caused by ischemiareperfusion. J Am Soc Nephrol 2004, 15:2115-2124. 10.1097/01.ASN.0000135059.67385.5D, 15284297.
23. Patel NSA, Sharples EJ, Cuzzocrea S, Chatterjee PK, Britti D, Yaqoob MM, Thiemermann C. Pretreatment with EPO reduces the injury and dysfunction caused by ischemia/reperfusion in the mouse kidney in vivo. Kidney Int 2004, 66:983-989. 10.1111/j.1523-1755.2004.00847.x, 15327391.
24. Vesey DA, Cheung C, Pat B, Endre Z, Gobé G, Johnson DW. Erythropoietin protects against ischemic acute renal injury. Nephrol Dial Transplant 2004, 19:348-355. 10.1093/ndt/gfg547, 14736958.
25. Spandou E, Tsouchnikas I, Karkavelas G, Dounousi E, Simeonidou C, Guiba- Tziampiri O, Tsakiris D. Erythropoietin attenuates renal injury in experimental acute renal failure ischaemic/reperfusion model. Nephrol Dial Transplant 2006, 21:330-336. 10.1093/ndt/gfi177, 16221709.
26. Johnson DW, Pat B, Vesey DA, Guan Z, Endre Z, Gobé GC. Delayed administration of darbeboietin or erythropoietin protects against ischemic acute renal injury and failure. Kidney Intern 2006, 69:1806-1813.
27. Romsi P, Rönka E, Kiviluoma K, Vainionpää V, Hirvonen J, Mennander A, Pokela M, Biancari F, Rimpiläinen J, Juvonen T. Potential neuroprotective benefits of erythropoietin during experimental hypothermic circulatory arrest. J Thorac Cardiovasc Surg 2002, 124:714-723. 10.1067/mtc.2002.123704, 12324729.
28. Givehchian M, Beschorner R, Ehmann C, Frauenlob L, Morgalla M, Hashemi B, Ziemer G, Scheule AM. Neuroprotective effects of erythropoietin during deep hypothermic circulatory arrest. Eur J Cardio-Thorac Surg 2010, 37:662-668.
29. Kristensen J, Maeng M, Rehling M, Berg JS, Mortensen UM, Nielsen SS, Nielsen TT. Lack of acute cardioprotective effect preischaemic erythropoietin administration in a porcine coronary occlusion model. Clin Physiol Funct Imaging 2005, 25:305-310. 10.1111/j.1475-097X.2005.00626.x, 16117735.
30. Hirata A, Minamino T, Asanuma H, Sanada S, Fujita M, Tsukamoto O, Wakeno M, Myoishi M, Okada K, Koyama H, Komamura K, Takashima S, Shinozaki Y, Mori H, Tomoike H, Hori M, Kitakaze M. Erythropoietin just before reperfusion reduces both lethal arrhythmias and infarct size via the phosphatidylinositol-3 kinase-dependent pathway in canine hearts. Cardiovasc Drugs Ther 2005, 19:33-40. 10.1007/s10557-005-6895-1, 15883754.
31. Hirata A, Minamino T, Asanuma H, Fujita M, Wakeno M, Myoishi M, Tsukamoto O, Okada K, Koyama H, Komamura K, Takashima S, Shinozaki Y, Mori H, Shiraga M, Kitakaze M, Hori M. Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs. J Am Coll Cardiol 2006, 48:176-184. 10.1016/j.jacc.2006.04.008, 16814664.
32. Krause KT, Jaquet K, Geidel S, Schneider C, Mandel C, Stoll HP, Hertting K, Harle T, Kuck KH. Percutaneous endocardial injection of erythropoietin: assessment of cardioprotection by electromechanical mapping. Eur J Heart Fail 2006, 8:443-450. 10.1016/j.ejheart.2005.10.017, 16464635.
33. Toma C, Letts DP, Tanabe M, Gorcsan J 3, Counihan PJ. Positive effect of darbepoetin on peri-infarction remodeling in a porcine model of myocardial ischemia-reperfusion. J Mol Cell Cardiol 2007, 43:130-136. 10.1016/j.yjmcc.2007.05.014, 17597149.
34. Schneider C, Jaquet K, Malisius R, Geidel S, Bahlmann E, Boczor S, Rau T, Antz M, Kuck KH, Krause K. Attenuation of cardiac remodeling by endocardial injection of erythropoietin: ultrasonic strain-rate imaging in a model of hibernating myocardium. European Heart J 2007, 28:499-509.
35. Angeli FS, Amabile N, Burjonroppa S, Shapiro M, Bartlett L, Zhang Y, Virmani R, Chatterjee K, Boyle A, Grossman W, Yeghiazarians Y. Prolonged therapy with erythropoietin is safe and prevents deterioration of left ventricular systolic function in a porcine model of myocardial infarction. J Cardiac Failure 2010, 16:579-589.
36. Chua S, Leu S, Lin YC, Sheu JJ, Sun CK, Chung SY, Chai HT, Lee FY, Kao YH, Wu CJ, Chang LT, Ko SF, Yip HK. Early erythropoietin therapy attenuates remodeling and preserves function of left ventricle in porcine myocardial infarction. J Invest Med 2010, 59:574-586.
37. Kawachi K, Iso Y, Sato T, Wakabayashi K, Kobayashi Y, Takeyama Y, Suzuki H. Effects of erythropoietin on angiogenesis after myocardial infarction in porcine. Heart Vessels 2012, 27:79-88. 10.1007/s00380-011-0197-2, 22038108.
38. Forman CJ, Johnson DW, Nicol DL. Erythropoietin administration protects against functional impairment and cell death after ischaemic renal injury in pigs. BJU Int 2006, 9:162-165.
39. Simon F, Scheuerle A, Calzia E, Bassi G, Öter S, Duy CN, Kick J, Brückner UB, Radermacher P, Schelzig H. Erythropoietin during porcine aortic balloon occlusion-induced ischemia/reperfusion injury. Crit Care Med 2008, 36:2143-2150. 10.1097/CCM.0b013e31817d7912, 18552697.
40. Maio R, Sepodes B, Patel NS, Thiemermann C, Mota-Filipe H, Costa P. Erythropoietin preserves the integrity and quality of organs for transplantation after cardiac death. Shock 2011, 35:126-133. 10.1097/SHK.0b013e3181e83236, 20523268.
41. Sølling C, Christensen AT, Krag S, Frøkiaer J, Wogensen L, Krog J, Tønnesen EK. Erythropoietin administration is associated with short term improvement in glomerular filtration rate after ischemia reperfusion injury. Acta Anaesthesiol Scand 2011, 55:185-195. 10.1111/j.1399-6576.2010.02369.x, 21226860.
42. Ishii Y, Sawada T, Murakami T, Sakuraoka Y, Shiraki T, Shimizu A, Kubota K, Fuchinoue S, Teraoka S. Renoprotective effect of erythropoietin against ischemia-reperfusion injury in a non-human primate model. Nephrol Dial Transplant 2011, 26:1157-1162. 10.1093/ndt/gfq601, 20935018.
43. Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Abraham E, MacIntyre NR, Shabot MM, Duh MS, Shapiro MJ. The CRIT Study: Anemia and blood transfusion in the ciritically ill - current clinical practice in the United States. Crit Care Med 2004, 32:39-52. 10.1097/01.CCM.0000104112.34142.79, 14707558.
44. Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Shapiro MJ, Corwin MJ, Colton T, . EPO Critical Care Trials Group Efficacy of recombinant human erythropoietin in critically ill patients. JAMA 2002, 288:2827-2835. 10.1001/jama.288.22.2827, 12472324, EPO Critical Care Trials Group.
45. Napolitano LM, Fabian TC, Kelly KM, Bailey JA, Block EF, Langholff W, Enny C, Corwin HL. Improved survival of critically ill patients treated with recombinant human erythropoietin. J Trauma 2008, 65:285-299. 10.1097/TA.0b013e31817f2c6e, 18695463.
46. Luchette FA, Pasquale MD, Fabian TC, Langholff WK, Wolfson M. A randomized, double blind, placebo-controlled study to assess the effect of recombinant human erythropoietin on functional outcomes in anemic, critically ill, trauma subjects: the Long Term Trauma Outcomes Study. Am J Surg 2012, 203:508-516. 10.1016/j.amjsurg.2011.08.006, 22177550.
47. Silver M, Corwin MJ, Bazan A, Gettinger A, Enny C, Corwin HL. Efficacy of recombinant human erythropoietin in critically ill patients admitted to a long-term acute care facility: a randomized, double-blind, placebo-controlled trial. Crit Care Med 2006, 34:2310-2316. 10.1097/01.CCM.0000233873.17954.42, 16878035.
48. Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Leczuk P, Stiefle M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Rüther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prnage H, Cerami A, Brines M, Sirén AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002, 8:495-505. 2040012, 12435860.
49. Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, Jähnig P, Herrmann M, Knauth M, Bähr M, Heide W, Wagner A, Schwab S, Reichmann H, Schwendemann G, Dengler R, Kastrup A, Bartels C, . for the EPO Stroke Trial Group Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 2009, 40:e647-e656. 10.1161/STROKEAHA.109.564872, 19834012, for the EPO Stroke Trial Group.
50. Yip HK, Tsai TH, Lin HS, Chen SF, Sun CK, Leu S, Yuen CM, Tan TY, Lan MY, Liou CW, Lu CH, Chang WN. Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke. Crit Care 2011, 15:R40. 10.1186/cc10002, 3221969, 21269484.
51. Minnerup J, Wersching H, Schäbitz WR. Erythropoietin for stroke treatment: dead or alive?. Crit Care 2011, 15:129. 10.1186/cc10057, 3219325, 21418552.
52. Stowell CP, Jones SC, Enny C, Langholff W, Leitz G. An open label, randomized, parallel-group study of perioperative epoietin alfa versus standard of care for blood conservation in major elective spinal cord surgery. Spine 2009, 34:2479-2485. 10.1097/BRS.0b013e3181bd163f, 19927096.
53. Najjar SS, Rao SV, Melloni C, Raman SV, Povsic TJ, Melton L, Barsness GW, Prather K, Heitner JF, Kilaru R, Gruberg L, Hasselblad V, Greenbaum AB, Patel M, Kim RJ, Talan M, Ferrucci L, Longo DL, Lakatta EG, Harrington RA, . REVEAL Investigators Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction. JAMA 2011, 305:1863-1872. 10.1001/jama.2011.592, 21558517, REVEAL Investigators.
54. Song YS, Lee T, You SJ, Chin HJ, Chae DW, Lim C, Park KH, Han S, Kim JH, Na KY. Prevention of acute kidney injury by Erythropoietin in patients undergoing coronary artery bypass grafting: a pilot study. Am J Nephrol 2009, 30:253-260. 10.1159/000223229, 19494484.
55. Endre ZH, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ, Hutchison R, Mehrtens JE, Robinson JM, Schollum JB, Westhuyzen J, Celi LA, McGinley RJ, Campbell IJ, George PM. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 2010, 77:1020-1030. 10.1038/ki.2010.25, 20164823.
56. Oh SW, Chin HJ, Chae DW, Na KY. Erythropoietin improves long-term outcomes in patients with acute kidney injury after coronary artery bypass grafting. J Korean Med Sci 2012, 27:506-511. 10.3346/jkms.2012.27.5.506, 3342541, 22563215.
57. Cachofeiro V, Goicochea M, García de Vinuesa S, Oubiña P, Lahera V, Luño J. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int 2008, 74(Suppl 111):S4-S9.
58. Jun M, LV J, Perkovic V, Jardine MJ. Managing cardiovascular risk in people with chronic kidney disease: a review of the evidence from randomized controlled trials. Ther Adv Chronic Dis 2011, 2:265-278.
59. d'Uscio LV, Smith LA, Santhanam AV, Richardson D, Nath K, Katusic ZS. Essential role of endothelial nitric oxide synthase in vascular effects of erythropoietin. Hypertension 2007, 49:1142-1148. 10.1161/HYPERTENSIONAHA.106.085704, 17372034.
60. Wever R, Boer P, Hijmering M, Verhaar M, Kastelein J, Versluis K, Lagerwerf F, van Rijn H, Koomans H, Rabelink T. Nitric oxide production is reduced in patients with chronic renal failure. Arterioscler Thromb Vasc Biol 1999, 19:1168-1172. 10.1161/01.ATV.19.5.1168, 10323766.
61. Weiner DE, Miskulin DC. Anemia managment in chronic kidney disease: bursting the hemoglobin bubble. Ann Intern Med 2010, 153:53-55.
62. Stenvinkel P, Bárány P. Anaemia, rHuEPO resistance, and cardiovascular disease in end-stage renal failure: links to inflammation and oxidative stress. Nephrol Dial Transplant 2002, 17(Suppl 5):32-37.
63. van der Putten K, Braam B, Yie KE, Gaillard CA. Mechanisms of disease: erythropoietin resistance in patients with both heart and kidney failure. Nat Clin Pract Nephrol 2008, 4:47-57. 10.1038/ncpneph0655, 18094727.
64. Santhanam AV, d'Uscio LV, Peterson TE, Katusic ZS. Activation of endothelial nitric oxide synthase is critical for erythropoietin-induced mobilization of progenitor cells. Peptides 2008, 29:1451-1455. 10.1016/j.peptides.2008.03.016, 2570495, 18448202.
65. Kawata T, Hashimoto S, Koike T. Effects of chronic nitric oxide synthase inhibition on renal function and histology in polycythemic rats. Kidney Blood Press Res 1998, 21:22-28. 10.1159/000025839, 9661133.
66. Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, Macleod M, Mignini LE, Jayaram P, Khan KS. Comparison of treatment affects between animal experiments and clinical trials: systemic review. BMJ 2007, 334:197. 10.1136/bmj.39048.407928.BE, 1781970, 17175568.
67. Turnbull IS, Wizorek JJ, Osborne D, Hotchkiss RS, Coopersmith CM, Buchman TG. Effects of age on mortality and antibiotic efficacy in cecal ligation and puncture. Shock 2003, 19:310-313. 10.1097/00024382-200304000-00003, 12688540.
68. Kawashima S, Yokoyama M. Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 2004, 24:998-1005. 10.1161/01.ATV.0000125114.88079.96, 15001455.