Prophylaxis with erythropoietin versus placebo reduces acute kidney injury and neutrophil gelatinase-associated lipocalin in patients undergoing cardiac surgery: a randomized, double-blind controlled trial

Abstract

BackgroundCardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication following coronary bypass graft (CABG) surgery. Multi-factorial causes of CSA-AKI involve oxidative stress and inflammation. Erythropoietin (EPO) has been shown from many studies to have a reno-protective effect. The present study was conducted to examine the role of EPO in preventing CSA-AKI.MethodsThis prospective, randomized, double-blind, placebo-controlled trial was conducted in the Cardiovascular and Thoracic Unit. One hundred patients randomly received either 200 U/kg of rHuEPO (n = 50) or saline (n = 50) intravenously three days before operation, and rHuEPO 100 U/kg or saline at operation time. The serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and urine neutrophil gelatinase-associated lipocaline (NGAL) were measured in order to evaluate renal injury following CABG.ResultsThe incidence of CSA-AKI was significantly lower in rHuEPO group (14%) when compared with the placebo group (38%; p < 0.01). The mean intensive care unit (ICU) and hospital stays of the rHuEPO group were significantly shorter than the placebo group (p < 0.01). Postoperative increases in SCr and decreases in eGFR were significantly lower in the rHuEPO group than the placebo group (p < 0.05). The mean urine NGAL in rHuEPO group was significantly lower than the placebo group at 3 hr, 6 hr, 12 hr and 18 hr after CABG (p < 0.05), respectively.ConclusionsProphylaxis administration with intravenous rHuEPO before cardiac surgery decreased the incidence of CSA-AKI and urine NGAL with reduced days in ICU and hospital in elective CABG patients.Trial registrationClinicalTrials.gov: NCT01066351

Erythropoiesis stimulating agents and reno-protection: a meta-analysis

“…Patients, all medical staff, & investigators were blinded to treatmentLow risk: Data Safety Monitoring Board with unmasking followed recording of the final AEs of the patient last enrolledLow riskLow risk: lost patients reportedLow risk: but 1 patient withdrewKim 2013 [27]AKI: DB, SSLow risk: computer-generated random codeLow risk: medications were prepared by a nurse who knew the patient’s group assignment but was not involved in the studyUnclear riskLow risk: No dropoutsLow risk: lost patients reportedLow risk: all patients treatedOh 2012 [16]AKI: DB, SSLow risk: A randomization code list with a block size of two was generated. Treatments were allocated to patients through the Internet in accordance with the predefined randomization listLow risk: a research coordinator performed randomization and prepared the study drugsUnclear riskLow riskLow risk: all patients completed the trialLow risk: all patients completed the trialTasanarong 2013 [28]AKI: DB, SSLow risk: treatment assignment by blocked randomization. Sealed envelopes containing the allocation group were opened by nurses who did not participate in the studyLow risk: treatments were blindly given to the research coordinator.…”

“…sCr at 2 weeks favored the ESA arm but did not reach statistical significance ( p  = 0.054). No difference in renal recovery or renal survivalTasanarong 2013 [28]Thailand (Thammasat Chalerm Prakiat Hospital)Patients scheduled for elective CABG using CPBepoetin β (200 U/kg; Recormon) 3 d before CABG and 100 U/kg at the operation time.Same volume & schedule of 0.9% saline N  = 100: ESA(50), control(50)≥0.3 mg/dl or ≥50% increase in sCr from baseline within the first 48 h post-operation according to the KDIGO 2012 criteria.No difference in Hb. sCr increase and eGFR decrease was lower in the ESA group.…”

Prognostic implications of preoperative chronic kidney disease and anemia in patients undergoing coronary artery bypass graft surgery

“…Weltert et al reported that the perioperative administration of human erythropoietin for 4 days significantly reduced blood transfusion and raised hemoglobin levels in patients undergoing off-pump CABG surgery [31]. Moreover, Tasanarong et al reported that prophylactic recombinant human erythropoietin administration before on-pump CABG surgery significantly reduced the occurrence of acute kidney injury and the length of hospital stay [32]. Although these studies did not focus on patients with CKD, their results suggest that ESA administration is a promising strategy for CAD patients with anemia and CKD.…”

Implementing the Kidney Disease

“…Three observational studies in cardiac surgery found that erythropoietin (EPO)-treated patients prevented AKI [59][60][61]. However, these results could not be confirmed in an early intervention study in ICU patients and in cardiac surgery patients [62 && ,63].…”