Table 2 Animal studies of EPO in nonischemic models of AKI
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 |