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

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

Remote conditioning or erythropoietin before surgery primes kidneys to clear ischemia-reperfusion-damaged cells: a renoprotective mechanism?

“…To date, preoperative administration of EPO and RIPC are two putative renoprotective interventions that have been studied in animal models and clinical trials. In early rodent (8,19,23,27), porcine (25) and clinical (26) studies, preoperative EPO administration showed promise for reducing aspects of AKI, but further clinical studies have subsequently proved disappointing (7,9). In contrast, a number of F875 RENOPROTECTION BY EPO OR RIPC clinical studies have shown that, after RIPC before surgery, acute injury to organs (either heart, liver, brain, or kidney) was significantly reduced (3,12,14,30), but negative results have also been reported (17,29).…”

“…A pilot clinical study reported encouraging preliminary results (26). However, substantial clinical evidence for renoprotection by EPO is lacking (7,9). In contrast, remote ischemic preconditioning (RIPC), in which short-term (1-5 min), nonlethal episodes (3-5 cycles) of limb ischemia remote to the organ of interest result in attenuated tissue injury during subsequent longer-term ischemia and reperfusion, has been reported to offer considerable protection against ischemia-reperfusion (IR)-induced organ damage.…”

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

“…First, as our results indicate, the percentage of patients requiring renal replacement therapy was higher in the current trial compared with other studies [11,12]. Thus, the employment of a single preventive strategy to mitigate the development of AKI may not be enough to inhibit the numerous interconnections of signaling pathways that lead to renal injury.…”

Endogenous erythropoietin varies significantly with inflammation-related proteins in extremely premature newborns

“…One finding that supports an anti-inflammatory role for EPO is that the biologic effects of EPO and TNF-α are antagonistic, each capable of suppressing the synthesis and activity of the other [31]. In addition, several animal studies have documented that the concentrations of pro-inflammatory proteins are reduced following EPO administration, [31–37] as is the expression of the genes for these proteins [5,38]. The pattern we see, then, could represent an anti-inflammatory response to the presence of pro-inflammatory cytokines, waxing and waning with the degree of inflammation.…”