Carbamylated erythropoietin-FC fusion protein and recombinant human erythropoietin during porcine kidney ischemia/reperfusion injury

Abstract

In swine with atherosclerosis, rhEPO and cEPO-FC failed to attenuate prolonged ischemia-induced kidney injury within an 8-h reperfusion period, possibly due to reduced EPO receptor expression resulting from pre-existing oxidative stress and/or reduced NO release.

Year in review in Intensive Care Medicine 2013: II. Sedation, invasive and noninvasive ventilation, airways, ARDS, ECMO, family satisfaction, end-of-life care, organ donation, informed consent, safety, hematological issues in critically ill patients

“…However, clinical studies yielded controversial results. Matějková et al [86] investigated whether the infusion of carbamylated erythropoietin-FC fusion protein (cEPO-FC) or rhEPO would protect against kidney I/R injury in pigs with atherosclerosis submitted to aortic occlusion. They observed no differences in markers of renal function, systemic inflammation and oxidative and nitrosative stress, as well as in histopatological apoptosis or glomerular and tubular damage among animals receiving cEPO-FC, rhEPO, or vehicle.…”

Kidney Ischemia and Reperfusion Injury – Field of Glory or Warterloo for Erythropoietin?

“…The reason for that controversal outcome was that the absolute number of EPO receptors in atherosclerotic renal tissue was up to 20 times lower as in the tissue of young and healthy animals. 23 Regarding all this results, both experimental and clinical, one must say that EPO might not have the effect that everyone desired. When looking at EPO and its effects on renal tissue, future experimental set-ups should take in account that most of the clinical problems are in patients of older age.…”

Alterações no perfil metabólico em resposta a isquemia/reperfusão renal em modelo suíno de lesão renal aguda

“…Estudos da NGAL em modelo suíno de isquemia detectaram aumento nas concentrações urinárias de animais isquêmicos (Silberstein et al 2013) - (Hunter et al 2012). Avaliações séricas de NGAL mostraram aumento desta em 48h pós transplante (Jochmans et al 2011) e após 8 horas de I/R bilateral de 120 minutos de isquemia com grande lesão (Matějková et al 2013). …”

“…Um desses modelos foi desenvolvido em suínos com a introdução do cateter-balão na artéria aorta abdominal, com o objetivo de ocluir ambas as artérias renais. No entanto, esta isquemia bilateral causou uma lesão renal acentuada, quando comparada ao nosso modelo, com danos glomerulares (dilatação do espaço de Bowman, inchaço da célula de Bowman capsular (Matějková et al 2013) e tubularização glomerular (Simon et al 2011). …”

“…Vários estudos têm descrito modelos de I/R unilateral com nefrectomia (Flacke et al 2012) (Hunter et al 2012) (Susa et al 2009) ou I/R renal bilateral (Matějková et al 2013) (Bhalodia et al 2009). No entanto, independente da técnica utilizada (PVA, clamp, cateter-balão) estes estudos têm mostrado um grau de lesão histológica inferior ao do nosso estudo, devido a esforços de compensação de um único rim ou pelo condicionamento pneumoperitonial pré-isquemia gerado pelo uso da técnica de laparoscopias (Weld et al 2008a).…”