Table 1 Animal studies of EPO in AKI: ischemia-reperfusion models
Year | Type | AKI model/follow-up | EPO dose | Outcome |
|---|---|---|---|---|
2009 | Dogs | IR: nephrectomy, 2 weeks recovery, then renal artery occlusion, ischemia 1 hr; reperfusion 28 days | EPO 500 U/kg i.v. before ischemia ± 90 min abdominal insufflation | ↓microalbuminuria, ↑renal function recovery at 4 weeks; i.v. EPO better than mannitol for renal I-R injury protection |
2009 | Rats | IR: transplanted with male bone marrow cells; reperfusion 2 or 4 weeks | EPO 5000 U 30 minutes before ischemia | ↑GFR (4 weeks), →proteinuria/Hb (2 and 4 weeks), ↓tubulointerstitial changes |
2008 | Rats | IR: occlusion of infrarenal abdominal aorta, ischemia 30 min, reperfusion 60 min vs. sham | EPO 1000 U/kg s.c. 5 min before ischemia | ↓MDA levels, ↓SOD activity, ↓catalase ↓histopathological changes |
2007 | Rats | IR: bilateral renal pedicle occlusion 1 day after last EPO injection, ischemia 45 min; reperfusion 24, 72 hr and 1 week | EPO 100 U/kg or 100 U/kg CEPO s.c. q. 2 days for 2 weeks vs. saline | CEPO: (no erythropoiesis) ↓apoptosis, ↓α-SMA expression, ↑tubular epithelial cell proliferation, ↓SCr. EPO: ↑Hb, ↓in apoptosis & α-SMA (not as marked as CEPO). CEPO more therapeutic than EPO. |
2007 | Rats | IR: bilateral renal pedicle occlusion 1 day after last EPO injection, ischemia 60 min; reperfusion 24, 72 hr | EPO 100 U/kg s.c. every 2 days for 2 weeks (6 injections) vs. saline | ↑HIF-1alpha-positive cells, ↑VEGF mRNA expression, ↓tubular hypoxia, ↓apoptotic and α-SMA-positive interstitial cells |
2008 | Rats | IR: bilateral renal pedicle occlusion 1 day after last EPO dose, ischemia 45 min; reperfusion 24, 72 hr and 1 week | EPO or CEPO as above for 2 weeks | ↑peritubular capillary endothelial cells. CEPO may protect kidneys from IR injury by promoting angiogenesis. |
2007 | Pigs | IR: unilateral nephrectomy; occlusion renal artery for 1 hr 1 week later, reperfusion 5 days | EPO 5000 U/kg IV at ischemia, then 1000 U/kg s.c. vs. no treatment | ↓renal dysfunction, ↓cell death (histology at 5 days) |
2006 | Rats | IR: bilateral renal pedicle occlusion, ischemia 45 min; reperfusion 48 hr | EPO 500 U/kg i.p. 20 min before ischemia | ↓SCr, ↓urea, ↓histological injury, ↓tubular apoptosis |
2006 | Rats | IR: bilateral renal pedicle occlusion, ischemia 45 min; reperfusion 1-7 days vs. sham/vehicle | EPO 5000 U/kg or DPO 25 μg/kg i.p. at time of ischemia or 6 hr after reperfusion | EPO & DPO at T0 and T6 -↓tubular apoptosis, ↓plasma creatinine/urea, ↑tubular regeneration (cell proliferation and mitosis) |
2005 | Rats | IR: R nephrectomy, clamp L pedicle 45 min and reperfusion 45 min and 24 hr | EPO 1000 U/kg and genistein (tyrosine kinase inhibitor) 10 mg/kg 2 hr before ischemia | ↓SCr, ↓urea, ↓TNF-α and IL-2 expression (proinflammatory mediators of I-R injury), ↓LDH (indicates lipid peroxidation), ↓histological injury; genistein reversed benefits of EPO |
2004 | Rats | IR: uni/bilateral renal artery occlusion, 30 min ischemia, 24 or 48 hr reperfusion vs. sham/vehicle | EPO 5000 U/kg i.p. 30 min before ischemia | ↓apoptosis, ↑regeneration, ↓casts, ↓plasma creatinine in vitro: ↓apoptosis, ↑mitosis/DNA synthesis |
2004 | Mice | IR: bilateral renal artery occlusion, 30 min ischemia, 24 hr reperfusion vs. sham/vehicle | EPO 1000 U/kg/day s.c. 3 days before I-R, or EPO 1000 U/kg s.c. on reperfusion | ↓plasma creatinine, ↓plasma AST, ↓histological injury, ↓kidney MPO and MDA levels |
2004 | Rats | IR: bilateral renal pedicle occlusion, 45 min ischemia, 6 hr reperfusion vs. sham/saline | EPO 300 U/kg i.v. 30 min before ischemia, 5 or 3 min before reperfusion | ↓tubular apoptosis, ↓tubular (NAG) and reperfusion (AST) injury, ↓histological injury, ↓SCr, better urine flow, ↑creatinine clearance |
2004 | Rats | IR: bilateral renal artery occlusion, 40 min ischemia, 48 (1) or 96 (2) hrs reperfusion vs. sham/vehicle | 1. EPO 200 U/kg i.p. at start. 6 and 24 hr after reperfusion; or 200 U/kg i.v. and 4, 10, 24, 48 hr after reperfusion | ↓plasma creatinine, ↓polyuria, ↓FENa, ↑AQP/NHE/TSC expression (prevented down-regulation of AQPs and Na+ transporters) |
2003 | Rats | IR: bilateral renal artery occlusion, 45 min ischemia, ≤72 hr reperfusion vs. sham/saline | EPO 3000 U/kg 24 hr pre I-R injury | ↓SCr, ↓tubular necrosis, ↓tubular apoptosis, ↓tubular cell proliferation ↑bcl-2 protein, ↓caspase 3 activity, ↓JNK expression, dose-dependent |
2001 | Rats | IR: R kidney occlusion, 30 or 45 min ischemia, simultaneous L nephrectomy, ≤ 96 hr reperfusion vs. sham/vehicle | EPO 500 or 3000 U/kg i.v. at ischemia then s.c. 24, 48 hr after | ↑HCt, ↓ mortality (severe ischemia group), →SCr/weight |