Abstract

BackgroundExperimentally, 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.MethodsIn 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.ResultsNo 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.ConclusionIn this randomized-controlled trial, α-Epoetin administrated after cardiac surgery, although safe, demonstrated neither nephroprotective nor anti-inflammatory properties.Trial registration numberNCT00676234

Highlights

  • Erythropoietin (EPO) has nephroprotective as well as immunomodulatory properties when administered after ischemic renal injury

  • All patients admitted in the intensive care unit (ICU) were first supposedly eligible for enrollment, only patients having “elective” cardiac surgery could be asked for consent prior to randomization and were included in this study

  • Outcome The primary outcome was the change in urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) concentration from baseline and 48 h after recombinant human EPO (r-HuEPO) injection

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Summary

Introduction

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. Acute kidney injury (AKI) is a frequent complication in the intensive care unit. In experimental models of ischemia-reperfusion, recombinant human EPO (r-HuEPO) injection before or during the injury appears to protect against acute de Seigneux et al BMC Nephrology 2012, 13:132 http://www.biomedcentral.com/1471-2369/13/132 kidney injury [5,6,7]. Even delayed administration of r-HuEPO, up to 6 hours after a renal ischemic injury, seems to be nephroprotective in rats [3]. The few data available in humans do not seem to reproduce this protective effect [8]

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