Skip to main content
Top
Published in: BMC Nephrology 1/2012

Open Access 01-12-2012 | Research article

Epoetin administrated after cardiac surgery: effects on renal function and inflammation in a randomized controlled study

Authors: Sophie de Seigneux, Belen Ponte, Lucien Weiss, Jérôme Pugin, Jacques André Romand, Pierre-Yves Martin, Patrick Saudan

Published in: BMC Nephrology | Issue 1/2012

Login to get access

Abstract

Background

Experimentally, erythropoietin (EPO) has nephroprotective as well as immunomodulatory properties when administered after ischemic renal injury. We tested the hypothesis that different doses of recombinant human EPO administered to patients after cardiac surgery would minimize kidney lesions and the systemic inflammatory response, thereby decreasing acute kidney injury (AKI) incidence.

Methods

In this double-blinded randomized control study, 80 patients admitted to the ICU post-cardiac surgery were randomized by computer to receive intravenously isotonic saline (n = 40) versus α-Epoetin (n = 40): either 40000 IU (n = 20) or 20000 IU (n = 20). The study lasted one year. The primary outcome was the change in urinary NGAL concentration from baseline and 48 h after EPO injection. Creatinine, cystatine C and urinary NGAL levels were measured on the day of randomization and 2–4 days after EPO injection. To assess acute inflammatory response, serum cytokines (IL6 and IL8) were measured at randomization and four days after r-HuEPO injection. Patients and care-takers were blinded for the assignment.

Results

No patient was excluded after randomization. Patient groups did not differ in terms of age, gender, comorbidities and renal function at randomization. The rate of AKI assessed by AKIN criteria was 22.5% in our population. EPO treatment did not significantly modify the difference in uNGAl between 48 hours and randomization compared to placebo [2.5 ng/ml (−17.3; 22.5) vs 0.7 ng/ml (−31.77; 25.15), p = 0.77] and the incidence of AKI was similar. Inflammatory cytokines levels were not influenced by EPO treatment. Mortality and hospital stays were similar between the groups and no adverse event was recorded.

Conclusion

In this randomized-controlled trial, α-Epoetin administrated after cardiac surgery, although safe, demonstrated neither nephroprotective nor anti-inflammatory properties.

Trial registration number

NCT00676234
Appendix
Available only for authorised users
Literature
1.
go back to reference Arcasoy MO: The non-haematopoietic biological effects of erythropoietin. Br J Haematol. 2008, 141 (1): 14-31. 10.1111/j.1365-2141.2008.07014.x.CrossRefPubMed Arcasoy MO: The non-haematopoietic biological effects of erythropoietin. Br J Haematol. 2008, 141 (1): 14-31. 10.1111/j.1365-2141.2008.07014.x.CrossRefPubMed
2.
go back to reference Brines M: The therapeutic potential of erythropoiesis-stimulating agents for tissue protection: a tale of two receptors. Blood Purif. 2010, 29 (2): 86-92. 10.1159/000245630.CrossRefPubMed Brines M: The therapeutic potential of erythropoiesis-stimulating agents for tissue protection: a tale of two receptors. Blood Purif. 2010, 29 (2): 86-92. 10.1159/000245630.CrossRefPubMed
3.
go back to reference Johnson DW, Pat B, Vesey DA, Guan Z, Endre Z, Gobe GC: Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure. Kidney Int. 2006, 69 (10): 1806-1813. 10.1038/sj.ki.5000356.CrossRefPubMed Johnson DW, Pat B, Vesey DA, Guan Z, Endre Z, Gobe GC: Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure. Kidney Int. 2006, 69 (10): 1806-1813. 10.1038/sj.ki.5000356.CrossRefPubMed
4.
go back to reference Uchino S, Kellum JA, Bellomo R, et al: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005, 294 (7): 813-818. 10.1001/jama.294.7.813.CrossRefPubMed Uchino S, Kellum JA, Bellomo R, et al: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005, 294 (7): 813-818. 10.1001/jama.294.7.813.CrossRefPubMed
5.
go back to reference Vesey DA, Cheung C, Pat B, Endre Z, Gobe G, Johnson DW: Erythropoietin protects against ischaemic acute renal injury. Nephrol Dial Transplant. 2004, 19 (2): 348-355. 10.1093/ndt/gfg547.CrossRefPubMed Vesey DA, Cheung C, Pat B, Endre Z, Gobe G, Johnson DW: Erythropoietin protects against ischaemic acute renal injury. Nephrol Dial Transplant. 2004, 19 (2): 348-355. 10.1093/ndt/gfg547.CrossRefPubMed
6.
go back to reference Sharples EJ, Patel N, Brown P, et al: Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol. 2004, 15 (8): 2115-2124. 10.1097/01.ASN.0000135059.67385.5D.CrossRefPubMed Sharples EJ, Patel N, Brown P, et al: Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol. 2004, 15 (8): 2115-2124. 10.1097/01.ASN.0000135059.67385.5D.CrossRefPubMed
7.
go back to reference Yang CW, Li C, Jung JY, et al: Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney. FASEB J. 2003, 17 (12): 1754-1755.PubMed Yang CW, Li C, Jung JY, et al: Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney. FASEB J. 2003, 17 (12): 1754-1755.PubMed
9.
go back to reference Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007, 11 (2): R31-10.1186/cc5713.CrossRefPubMedPubMedCentral Mehta RL, Kellum JA, Shah SV, et al: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007, 11 (2): R31-10.1186/cc5713.CrossRefPubMedPubMedCentral
10.
go back to reference Ricci Z, Cruz D, Ronco C: The RIFLE classification for acute kidney injury definition. Am J Surg. 2009, 198 (1): 152-153. 10.1016/j.amjsurg.2008.06.033.CrossRefPubMed Ricci Z, Cruz D, Ronco C: The RIFLE classification for acute kidney injury definition. Am J Surg. 2009, 198 (1): 152-153. 10.1016/j.amjsurg.2008.06.033.CrossRefPubMed
11.
go back to reference Mariscalco G, Lorusso R, Dominici C, Renzulli A, Sala A: Acute kidney injury: a relevant complication after cardiac surgery. Ann Thorac Surg. 2011, 92 (4): 1539-1547. 10.1016/j.athoracsur.2011.04.123.CrossRefPubMed Mariscalco G, Lorusso R, Dominici C, Renzulli A, Sala A: Acute kidney injury: a relevant complication after cardiac surgery. Ann Thorac Surg. 2011, 92 (4): 1539-1547. 10.1016/j.athoracsur.2011.04.123.CrossRefPubMed
12.
go back to reference Lassnigg A, Schmidlin D, Mouhieddine M, et al: Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol. 2004, 15 (6): 1597-1605. 10.1097/01.ASN.0000130340.93930.DD.CrossRefPubMed Lassnigg A, Schmidlin D, Mouhieddine M, et al: Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol. 2004, 15 (6): 1597-1605. 10.1097/01.ASN.0000130340.93930.DD.CrossRefPubMed
13.
go back to reference Haase M, Bellomo R, Devarajan P, et al: Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults. Ann Thorac Surg. 2009, 88 (1): 124-130. 10.1016/j.athoracsur.2009.04.023.CrossRefPubMed Haase M, Bellomo R, Devarajan P, et al: Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults. Ann Thorac Surg. 2009, 88 (1): 124-130. 10.1016/j.athoracsur.2009.04.023.CrossRefPubMed
14.
go back to reference Haase M, Devarajan P, Haase-Fielitz A, et al: The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011, 57 (17): 1752-1761. 10.1016/j.jacc.2010.11.051.CrossRefPubMedPubMedCentral Haase M, Devarajan P, Haase-Fielitz A, et al: The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011, 57 (17): 1752-1761. 10.1016/j.jacc.2010.11.051.CrossRefPubMedPubMedCentral
15.
go back to reference Koyner JL, Vaidya VS, Bennett MR, et al: Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol. 2010, 5 (12): 2154-2165. 10.2215/CJN.00740110.CrossRefPubMedPubMedCentral Koyner JL, Vaidya VS, Bennett MR, et al: Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol. 2010, 5 (12): 2154-2165. 10.2215/CJN.00740110.CrossRefPubMedPubMedCentral
16.
go back to reference Park M, Coca SG, Nigwekar SU, Garg AX, Garwood S, Parikh CR: Prevention and treatment of acute kidney injury in patients undergoing cardiac surgery: a systematic review. Am J Nephrol. 2010, 31 (5): 408-418. 10.1159/000296277.CrossRefPubMedPubMedCentral Park M, Coca SG, Nigwekar SU, Garg AX, Garwood S, Parikh CR: Prevention and treatment of acute kidney injury in patients undergoing cardiac surgery: a systematic review. Am J Nephrol. 2010, 31 (5): 408-418. 10.1159/000296277.CrossRefPubMedPubMedCentral
17.
go back to reference Chawla LS, Seneff MG, Nelson DR, et al: Elevated plasma concentrations of IL-6 and elevated APACHE II score predict acute kidney injury in patients with severe sepsis. Clin J Am Soc Nephrol. 2007, 2 (1): 22-30.CrossRefPubMed Chawla LS, Seneff MG, Nelson DR, et al: Elevated plasma concentrations of IL-6 and elevated APACHE II score predict acute kidney injury in patients with severe sepsis. Clin J Am Soc Nephrol. 2007, 2 (1): 22-30.CrossRefPubMed
18.
go back to reference Gueret G, Lion F, Guriec N, et al: Acute renal dysfunction after cardiac surgery with cardiopulmonary bypass is associated with plasmatic IL6 increase. Cytokine. 2009, 45 (2): 92-98. 10.1016/j.cyto.2008.11.001.CrossRefPubMed Gueret G, Lion F, Guriec N, et al: Acute renal dysfunction after cardiac surgery with cardiopulmonary bypass is associated with plasmatic IL6 increase. Cytokine. 2009, 45 (2): 92-98. 10.1016/j.cyto.2008.11.001.CrossRefPubMed
19.
go back to reference Bian XX, Yuan XS, Qi CP: Effect of recombinant human erythropoietin on serum S100B protein and interleukin-6 levels after traumatic brain injury in the rat. Neurol Med Chir (Tokyo). 2010, 50 (5): 361-366. 10.2176/nmc.50.361.CrossRef Bian XX, Yuan XS, Qi CP: Effect of recombinant human erythropoietin on serum S100B protein and interleukin-6 levels after traumatic brain injury in the rat. Neurol Med Chir (Tokyo). 2010, 50 (5): 361-366. 10.2176/nmc.50.361.CrossRef
20.
go back to reference Shen Y, Wang Y, Li D, et al: Recombinant human erythropoietin pretreatment attenuates heart ischemia-reperfusion injury in rats by suppressing the systemic inflammatory response. Transplant Proc. 2010, 42 (5): 1595-1597. 10.1016/j.transproceed.2009.11.050.CrossRefPubMed Shen Y, Wang Y, Li D, et al: Recombinant human erythropoietin pretreatment attenuates heart ischemia-reperfusion injury in rats by suppressing the systemic inflammatory response. Transplant Proc. 2010, 42 (5): 1595-1597. 10.1016/j.transproceed.2009.11.050.CrossRefPubMed
21.
go back to reference Licker M, Diaper J, Cartier V, et al: Clinical Review: Management of weaning from cardiopulmonary bypass after cardiac surgery. Ann Card Anaesth. 2012, 15 (3): 206-223. 10.4103/0971-9784.97977.CrossRefPubMed Licker M, Diaper J, Cartier V, et al: Clinical Review: Management of weaning from cardiopulmonary bypass after cardiac surgery. Ann Card Anaesth. 2012, 15 (3): 206-223. 10.4103/0971-9784.97977.CrossRefPubMed
22.
go back to reference Pedersen KR, Ravn HB, Hjortdal VE, Norregaard R, Povlsen JV: Neutrophil gelatinase-associated lipocalin (NGAL): validation of commercially available ELISA. Scand J Clin Lab Invest. 2010, 70 (5): 374-382. 10.3109/00365513.2010.486868.CrossRefPubMed Pedersen KR, Ravn HB, Hjortdal VE, Norregaard R, Povlsen JV: Neutrophil gelatinase-associated lipocalin (NGAL): validation of commercially available ELISA. Scand J Clin Lab Invest. 2010, 70 (5): 374-382. 10.3109/00365513.2010.486868.CrossRefPubMed
23.
go back to reference Song YR, Lee T, You SJ, et al: Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: a pilot study. Am J Nephrol. 2009, 30 (3): 253-260. 10.1159/000223229.CrossRefPubMed Song YR, Lee T, You SJ, et al: Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: a pilot study. Am J Nephrol. 2009, 30 (3): 253-260. 10.1159/000223229.CrossRefPubMed
24.
go back to reference Endre ZH, Walker RJ, Pickering JW, et al: Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int. 2010, 77 (11): 1020-1030. 10.1038/ki.2010.25.CrossRefPubMed Endre ZH, Walker RJ, Pickering JW, et al: Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int. 2010, 77 (11): 1020-1030. 10.1038/ki.2010.25.CrossRefPubMed
25.
go back to reference Martinez F, Kamar N, Pallet N, et al: High dose epoetin beta in the first weeks following renal transplantation and delayed graft function: Results of the Neo-PDGF Study. Am J Transplant. 2010, 10 (7): 1695-1700. 10.1111/j.1600-6143.2010.03142.x.CrossRefPubMed Martinez F, Kamar N, Pallet N, et al: High dose epoetin beta in the first weeks following renal transplantation and delayed graft function: Results of the Neo-PDGF Study. Am J Transplant. 2010, 10 (7): 1695-1700. 10.1111/j.1600-6143.2010.03142.x.CrossRefPubMed
26.
go back to reference Hall IE, Coca SG, Perazella MA, et al: Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis. Clin J Am Soc Nephrol. 2011, 6 (12): 2740-2749. 10.2215/CJN.04960511.CrossRefPubMedPubMedCentral Hall IE, Coca SG, Perazella MA, et al: Risk of Poor Outcomes with Novel and Traditional Biomarkers at Clinical AKI Diagnosis. Clin J Am Soc Nephrol. 2011, 6 (12): 2740-2749. 10.2215/CJN.04960511.CrossRefPubMedPubMedCentral
27.
go back to reference Mishra J, Dent C, Tarabishi R, et al: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005, 365 (9466): 1231-1238. 10.1016/S0140-6736(05)74811-X.CrossRefPubMed Mishra J, Dent C, Tarabishi R, et al: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005, 365 (9466): 1231-1238. 10.1016/S0140-6736(05)74811-X.CrossRefPubMed
28.
go back to reference Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA: Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant. 2008, 23 (6): 1970-1974. 10.1093/ndt/gfm908.CrossRefPubMed Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA: Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant. 2008, 23 (6): 1970-1974. 10.1093/ndt/gfm908.CrossRefPubMed
29.
go back to reference Solling C, Christensen AT, Krag S, et al: Erythropoietin administration is associated with short-term improvement in glomerular filtration rate after ischemia-reperfusion injury. Acta Anaesthesiol Scand. 2011, 55 (2): 185-195. 10.1111/j.1399-6576.2010.02369.x.CrossRefPubMed Solling C, Christensen AT, Krag S, et al: Erythropoietin administration is associated with short-term improvement in glomerular filtration rate after ischemia-reperfusion injury. Acta Anaesthesiol Scand. 2011, 55 (2): 185-195. 10.1111/j.1399-6576.2010.02369.x.CrossRefPubMed
30.
go back to reference Liu KD, Altmann C, Smits G, et al: Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case–control study. Crit Care. 2009, 13 (4): R104-10.1186/cc7940.CrossRefPubMedPubMedCentral Liu KD, Altmann C, Smits G, et al: Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case–control study. Crit Care. 2009, 13 (4): R104-10.1186/cc7940.CrossRefPubMedPubMedCentral
Metadata
Title
Epoetin administrated after cardiac surgery: effects on renal function and inflammation in a randomized controlled study
Authors
Sophie de Seigneux
Belen Ponte
Lucien Weiss
Jérôme Pugin
Jacques André Romand
Pierre-Yves Martin
Patrick Saudan
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2012
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/1471-2369-13-132

Other articles of this Issue 1/2012

BMC Nephrology 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.