Erythropoietin does not attenuate renal dysfunction or inflammation in a porcine model of endotoxemia.

BACKGROUND: Erythropoietin (EPO) is a multifunctional cytokine with anti-apoptotic, anti-inflammatory, and organ protective effects. EPO protects against ischemia-reperfusion injuries, and recent reports suggest that EPO also prevents organ dysfunction in experimental sepsis. The aims of this study were to determine whether EPO prevents endotoxemia-induced organ dysfunction in a porcine model and to characterize the immunomodulatory and anti-apoptotic effects of EPO. METHODS: Twenty-eight pigs were randomly assigned to three groups: (1) endotoxemia treated with EPO 5000 IU/kg, (2) endotoxemia treated with placebo, and (3) a sham group anesthetized and submitted to sham operation without treatment. A laparotomy was performed, and a flow probe was placed around the left renal artery, which allowed renal blood flow (RBF) measurements. Endotoxemia was induced by an infusion of lipopolysaccharide. After 2 h, the infusion was reduced to a maintenance dose and the animals were fluid resuscitated. The glomerular filtration rate (GFR), RBF, renal oxygen consumption, and plasma cytokines [interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha] were analyzed. Renal biopsies were analyzed for cytokine content and apoptosis. RESULTS: Endotoxemia elicited impaired renal function, estimated as GFR, and increased the levels of renal apoptotic cells, with no modifying effect of EPO. Furthermore, EPO had no effect on RBF, renal oxygen consumption, or the systemic hemodynamic response to endotoxemia. EPO did not modify the inflammatory response, measured as changes in cytokine levels in plasma and organs. CONCLUSION: EPO did not confer renal protection in this fluid-resuscitated porcine model of endotoxemia, and EPO did not modify the inflammatory response.

Erythropoietin administration is associated with short-term improvement in glomerular filtration rate after ischemia-reperfusion injury.

BACKGROUND: Erythropoietin (EPO) is a cytokine with organ-protective properties. We hypothesized that EPO could attenuate acute renal dysfunction and inflammation in a porcine model of ischemia-reperfusion (IR). Furthermore, we aimed to characterize the impact of EPO on systemic and renal hemodynamics, and renal oxygen consumption. METHODS: Twenty-four pigs were randomly assigned to three groups: (1) EPO (5000 IU/kg) administered intravenously before IR (n=9), (2) placebo administered before IR (n=9), or (3) sham group, anesthetized and operated on only (n=6). IR was induced by clamping the left renal artery for 45 min. Hemodynamics and renal blood flow (RBF) were analyzed continuously. Glomerular filtration rate (GFR), renal oxygen consumption, and plasma cytokines (IL-1ß, IL-6, IL-8, IL-10, and TNF-α) were analyzed hourly. Renal biopsies were analyzed for cytokine content and apoptosis. RESULTS: GFR was higher during reperfusion in the EPO group than in the placebo group (P<0.01). No differences between the IR groups were found in hemodynamics, RBF, oxygen consumption, or renal apoptosis. The levels of TNF-α in the plasma (P=0.036) and the levels of TNF-α and IL-10 in the renal cortex (P=0.04 and P=0.01, respectively) were lower in the EPO group compared with the sham group. CONCLUSION: EPO attenuated the renal dysfunction as estimated as GFR. This effect was not related to changes in the hemodynamics. The immunomodulatory effects of EPO were manifested as decreased levels of TNF-α and IL-10 in renal biopsies and TNF-α levels in plasma.