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Table 1 Animal studies of EPO in AKI: ischemia-reperfusion models

From: Erythropoietin (EPO) in acute kidney injury

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
  1. IR = ischemia-reperfusion, ↑ = increased, ↓ = decrease(d), → = the same level, MDA = malondialdehyde, SOD = superoxide dismutase (an antioxidant), CEPO = carbamylated EPO, α-SMA = alpha-smooth muscle actin (associated with renal injury), SCr = serum creatinine, HIF-1 alpha = hypoxia inducible factor-alpha, VEGF = vascular endothelial growth factor, mRNA = messenger RNA, DPO = darbepoietin, R = right, L = left, TNF-α = tumor necrosis factor-alpha, IL-2 = interleukin-2, LDH = lactate dehydrogenase, PTC = proximal tubule cell, AST = aspartate aminotransferase (indicates reperfusion injury), MPO = myeloperoxidase, NAG = N-acetylglutamate, FENa = fractional excretion of Na+, AQP = aquaporin, NHE = Na+/H+ exchanger, TSC = thiazide-sensitive sodium chloride cotransporter, bcl-2 = oncogene activated by chromosome translocation in human B-cell lymphomas, JNK = c-Jun N-terminal kinase, HSP70 = heat shock protein 70