Skip to main content

Table 2 Animal studies of EPO in nonischemic models of AKI

From: Erythropoietin (EPO) in acute kidney injury

Year Type AKI model EPO dose Outcome
2010 Rats Brain death + Perfused kidney model 10 μg/kg EPO or CEPO IV, 4 hr brain death, then kidney reperfusion in perfused kidney model EPO and CEPO: ↓expression of proinflammatory genes, ↓infiltration of polymorphonuclear cells in kidney, preserved vascular integrity. CEPO more effective than EPO. Kidney function fully restored with EPO and CEPO.
2010 Mice Aristolochic acid nephropathy DPO 0.1 mcg/kg wkly from day of Aristolochic acid administration or on day 28 ↑survival of tubular cells lead to ↓acute tubular injury, interstitial inflammation and interstitial fibrosis.
2008 Rats CIN: Ioversol 2.9 g/kg iodine + inhibition of prostaglandin and NO synthesis EPO 10,000 U/kg or asialoEPO 80 ng/g i.v. 1 hr before Ioversol ↓renal dysfunction and histological injury, ↓apoptosis, ↓caspase3-activated apoptosis in renal porcine epithelial cells in vitro with ↑JAK2/STAT5 phosphorylation and HSP70 expression; ↑JAK2/STAT5 phosphorylation and HSP70 expression in rat kidneys in vivo.
2008 Rats in vitro /CIN: cisplatin 5.5 mg/kg i.v. EPO 5,000 U/kg i.v. OR equivalent peptide mass of inactive EPO OR DPO 25 μg/kg before cisplatin OR saline EPO ↑HCt, ↓SCr; DPO also ↑HCt, ↓SCr. Clearance studies: GFR and renal blood flow confirmed DPO renal protection. ↓tubular apoptosis and necrosis with DPO. DPO 48 hr after cisplatin was renoprotective.
2008 Mice CIN: i.p. cisplatin injection (10 mg/kg/day) for 2 days vs. placebo. Follow-up 6 days. EPO 1,000 U/kg i.p. daily ≤ 3 days before cisplatin vs. vehicle ↓urea, ↓casts, ↑marrow stem cell (MSC) numbers
2007 Mice Endotoxemia: 2.5 mg/kg endotoxin i.p. (lipopolysaccharide); follow-up 16 hrs later EPO 4000 U/kg 30 min before endotoxin vs. vehicle ↑GFR (inulin clearance), →MAP, →Renal bld flow, ↑CRP, →serum NO, EPO reversed the endotoxin effect on renal SOD activity (SOD ↓ in control group).
2006 Rats CIN: (iothalamate), following indomethacin and Nω nitro-L-arginine methyl ester EPO 3000 U/kg and 600 U/kg i.v. 24 and 2 hr pre-CIN induction vs. saline Creatinine clearance preserved
2005 Rats Chronic kidney disease DPO s.c. 0.4 μg/kg/wk into 5/6 remnant kidney rats after renal mass reduction ↑microvascular density, ↑endothelial proliferation, preserved renal function (↓SCr), ↓scarring, ↑VEGF expression
2004 Rats Hemorrhagic shock and endotoxic shock EPO 300 U/kg i.v. before resuscitation ↓renal dysfunction in hemorrhagic but not endotoxic shock
2001 Rats CIN: cisplatin toxicity - i.p. cisplatin injection 6 mg/kg vs. placebo EPO 100 U/kg i.p. before cisplatin, then daily for 9 days vs. placebo ↑renal blood flow/GFR at 9 days, ↑ tubular regeneration, ↑tubular cell proliferation, ↑functional recovery
1994 Rats CIN: cisplatin toxicity - i.p. cisplatin injection 7 mg/kg vs. placebo EPO 100 U/kg i.p. after cisplatin, then daily for 9 days vs. placebo ↑functional recovery, ↑tubular regeneration, ↑DNA synthesis
  1. CEPO = carbamylated EPO, DPO = darbepoietin, ↑ = increased, ↓ = decrease(d), → = same level, H2O2 = hydrogen peroxide, JAK2/STAT5/Akt = signaling pathways of EPO, GSK-3β = glycogen synthase kinase 3 beta, mTOR = mammalian target of rapamycin, ERK = extracellular signal-regulated kinase, CIN = contrast-induced nephropathy, NO = nitric oxide, HSP70 = heat shock protein 70, RPTE = renal proximal tubular epithelial, SCr = serum creatinine, MAP = mean arterial pressure, SOD = superoxide dismutase (an antioxidant), VEGF = vascular endothelial growth factor