Effect of erythropoietin on the incidence of acute kidney injury following complex valvular heart surgery: a double blind, randomized clinical trial of efficacy and safety

Abstract

IntroductionRecombinant human erythropoietin (EPO) is known to provide organ protection against ischemia-reperfusion injury through its pleiotropic properties. The aim of this single-site, randomized, case-controlled, and double-blind study was to investigate the effect of pre-emptive EPO administration on the incidence of postoperative acute kidney injury (AKI) in patients with risk factors for AKI undergoing complex valvular heart surgery.MethodsWe studied ninety-eight patients with preoperative risk factors for AKI. The patients were randomly allocated to either the EPO group (n = 49) or the control group (n = 49). The EPO group received 300 IU/kg of EPO intravenously after anesthetic induction. The control group received an equivalent volume of normal saline. AKI was defined as an increase in serum creatinine >0.3 mg/dl or >50% from baseline. Biomarkers of renal injury were serially measured until five days postoperatively.ResultsPatient characteristics and operative data, including the duration of cardiopulmonary bypass, were similar between the two groups. Incidence of postoperative AKI (32.7% versus 34.7%, P = 0.831) and biomarkers of renal injury including cystatin C and neutrophil gelatinase-associated lipocalin showed no significant differences between the groups. The postoperative increase in interleukin-6 and myeloperoxidase was similar between the groups. None of the patients developed adverse complications related to EPO administration, including thromboembolic events, throughout the study period.ConclusionsIntravenous administration of 300 IU/kg of EPO did not provide renal protection in patients who are at increased risk of developing AKI after undergoing complex valvular heart surgery.Trial registrationClinical Trial.gov, NCT01758861

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

“…Investigators and patients were blinded to the treatmentHigh riskLow risk: AKI data on all patientsLow risk: lost patients reportedLow risk: all patients treatedEndre 2010 [26]AKI: DB, MS (2 centers)Low risk: allocation by a predefined computer-generated randomization sequenceLow risk: concealment was by a pharmacist; pairs of identical syringes. 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.…”

“…Four of the trials were performed by overlapping members of the same study groups [16, 17, 27, 29]. Song (2009) and Oh (2012) analyzed the same 71 patients and patient data, but used different definitions of AKI.…”

Renal Failure and Heart Surgery

“…A list of attempted and failed strategies to prevent CSA-AKI includes:diuretics (furosemide, mannitol) [29]; renal vasodilators (dopamine, fenoldopan, Ca channel blockers); atrial natriuretic peptides (nesiritide); anti-oxidants (N-acetylcysteine); ACE-inhibitors [30]; anti-inflammatory drugs (steroids); ultrafiltration; anti-apoptotic agents; urinary alkalinization by sodium bicarbonate [31]; statins [32]; human recombinant erythropoietin [33]; and remote ischemic pre conditioning [34]. Trials conducted on renotropic progenitor cells administration were prematurely terminated by the company (AlloCure).…”

Erythropoietin in traumatic brain injury associated acute kidney injury: A randomized controlled trial

“…Recombinant erythropoietin (EPO) has been shown to have renal protective effects in experimental studies . The use EPO for prevention of AKI has been studied in patients undergoing cardiac surgery and following renal transplantation, but thus far the data are conflicting . No studies have assessed the effect of EPO on kidney function in patients with trauma .…”