Erythropoietin improves long-term outcomes in patients with acute kidney injury after coronary artery bypass grafting

Se Won Oh, Ho Jun Chin, Dong Wan Chae, Ki Young Na, Se Won Oh, Ho Jun Chin, Dong Wan Chae, Ki Young Na

Abstract

Previous studies reported the beneficial effect of erythropoietin (EPO) in acute injuries. We followed patients with and without acute kidney injury (AKI) after coronary artery bypass grafting (CABG) and evaluated the effect of EPO on long-term outcome. We also assessed the efficacy of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. Seventy-one patients scheduled for elective CABG were randomly given either 300 U/kg of EPO or saline before CABG. The primary outcome was AKI, and the secondary outcome was the all-cause-mortality and composite of all-cause-mortality and end stage renal disease (ESRD). Twenty-one patients had AKI, 14 (66.7%) in the placebo group and 7 (33.3%) in the EPO group (P = 0.05). Also, uNGAL was higher in the patients with AKI than in those without AKI at baseline, 2, 4, 24, and 72 hr after CABG (P = 0.011). Among patients with AKI, 2-week creatinine (Cr) was not different from baseline Cr in the EPO group, but 2-week Cr was significantly higher than baseline Cr in the placebo group (P = 0.009). All-cause-mortality (P = 0.022) and the composite of all-cause-mortality and ESRD (P = 0.003) were reduced by EPO. EPO reduces all-cause-mortality and ESRD in patients with AKI, largely due to the beneficial effect of EPO on recovery after AKI.

Keywords: Erythropoietin; Mortality; Neutrophil Gelatinase-Associated Lipocalin Protein.

Figures

Fig. 1
Fig. 1
Changes of serum creatinine after coronary artery bypass grafting in patients with AKI. *P < 0.05 vs 0 days, both EPO and placebo group; †P < 0.05 vs 0 days, placebo group only. Error bars show the standard deviation of mean.
Fig. 2
Fig. 2
Kaplan-Meier curves for composite outcome of mortality or ESRD. Participants were classified according to the development of AKI and the administration of EPO: group A, AKI in EPO group; group B, no AKI in placebo group; group C, no AKI in EPO group; group D, AKI in placebo group.

References

    1. Maxwell PH, Osmond MK, Pugh CW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJ, Johnson MH, Ratcliffe PJ. Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int. 1993;44:1149–1162.
    1. Weidemann A, Johnson RS. Nonrenal regulation of EPO synthesis. Kidney Int. 2009;75:682–688.
    1. Warren JS, Zhao Y, Yung R, Desai A. Recombinant human erythropoietin suppresses endothelial cell apoptosis and reduces the ratio of Bax to Bcl-2 proteins in the aortas of apolipoprotein E-deficient mice. J Cardiovasc Pharmacol. 2011;57:424–433.
    1. Toba H, Nakashima K, Oshima Y, Kojima Y, Tojo C, Nakano A, Wang J, Kobara M, Nakata T. Erythropoietin prevents vascular inflammation and oxidative stress in subtotal nephrectomized rat aorta beyond haematopoiesis. Clin Exp Pharmacol Physiol. 2010;37:1139–1146.
    1. Malgorzewicz S, Lichodziejewska-Niemierko M, Lizakowski S, Liberek T, Lysiak-Szydlowska W, Rutkowski B. Oxidative stress, inflammation and nutritional status during darbepoetin alpha treatment in peritoneal dialysis patients. Clin Nephrol. 2010;73:210–215.
    1. Ozawa T, Toba K, Suzuki H, Kato K, Iso Y, Akutsu Y, Kobayashi Y, Takeyama Y, Kobayashi N, Yoshimura N, et al. Single-dose intravenous administration of recombinant human erythropoietin is a promising treatment for patients with acute myocardial infarction: randomized controlled pilot trial of EPO/AMI-1 study. Circ J. 2010;74:1415–1423.
    1. Haljan G, Maitland A, Buchan A, Arora RC, King M, Haigh J, Culleton B, Faris P, Zygun D. The erythropoietin neuroprotective effect: assessment in CABG surgery (TENPEAKS): a randomized, double-blind, placebo controlled, proof-of-concept clinical trial. Stroke. 2009;40:2769–2775.
    1. Song YR, 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.
    1. 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;69:1806–1813.
    1. Lee DW, Kwak IS, Lee SB, Song SH, Seong EY, Yang BY, Lee MY, Sol MY. Post-treatment effects of erythropoietin and nordihydroguaiaretic acid on recovery from cisplatin-induced acute renal failure in the rat. J Korean Med Sci. 2009;24:S170–S175.
    1. Kim SS, Lee KH, Sung DK, Shim JW, Kim MJ, Jeon GW, Chang YS, Park WS. Erythropoietin attenuates brain injury, subventricular zone expansion, and sensorimotor deficits in hypoxic-ischemic neonatal rats. J Korean Med Sci. 2008;23:484–491.
    1. Lee JH, Sung DK, Koo SH, Shin BK, Hong YS, Son CS, Lee JW, Chang YS, Park WS. Erythropoietin attenuates hyperoxia-induced lung injury by down-modulating inflammation in neonatal rats. J Korean Med Sci. 2007;22:1042–1047.
    1. James MT, Ghali WA, Knudtson ML, Ravani P, Tonelli M, Faris P, Pannu N, Manns BJ, Klarenbach SW, Hemmelgarn BR Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) Investigators. Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography. Circulation. 2011;123:409–416.
    1. Mehta RH, Honeycutt E, Patel UD, Lopes RD, Shaw LK, Glower DD, Harrington RA, Califf RM, Sketch MH., Jr Impact of recovery of renal function on long-term mortality after coronary artery bypass grafting. Am J Cardiol. 2010;106:1728–1734.
    1. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005;365:1231–1238.
    1. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A NGAL Meta-analysis Investigator Group. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;54:1012–1024.
    1. Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O, Philipp T, Kribben A. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004;66:1115–1122.
    1. Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol. 2007;18:407–413.
    1. Korean Statistical Information Service. KOSIS. [accessed on 22 September 2011]. Available at .
    1. Kim SY, Jin DC, Bang BK. Current status of dialytic therapy in Korea. Nephrology (Carlton) 2003;8:S2–S9.
    1. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.
    1. Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol. 2006;1:19–32.
    1. Liangos O, Tighiouart H, Perianayagam MC, Kolyada A, Han WK, Wald R, Bonventre JV, Jaber BL. Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers. 2009;14:423–431.
    1. Han WK, Wagener G, Zhu Y, Wang S, Lee HT. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol. 2009;4:873–882.
    1. Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, et al. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke. 2009;40:e647–e656.
    1. Endre ZH, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ, Hutchison R, Mehrtens JE, Robinson JM, Schollum JB, et al. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial) Kidney Int. 2010;77:1020–1030.
    1. Munshi R, Johnson A, Siew ED, Ikizler TA, Ware LB, Wurfel MM, Himmelfarb J, Zager RA. MCP-1 gene activation marks acute kidney injury. J Am Soc Nephrol. 2011;22:165–175.
    1. Thrailkill KM, Moreau CS, Cockrell GE, Jo CH, Bunn RC, Morales-Pozzo AE, Lumpkin CK, Fowlkes JL. Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus. Endocrine. 2010;37:336–343.
    1. Nickolas TL, Barasch J, Devarajan P. Biomarkers in acute and chronic kidney disease. Curr Opin Nephrol Hypertens. 2008;17:127–132.
    1. Meijer E, Boertien WE, Nauta FL, Bakker SJ, van Oeveren W, Rook M, van der Jagt EJ, van Goor H, Peters DJ, Navis G, et al. Association of urinary biomarkers with disease severity in patients with autosomal dominant polycystic kidney disease: a cross-sectional analysis. Am J Kidney Dis. 2010;56:883–895.

Source: PubMed

3
Abonnere