Table 3 Pre-clinical data on effects of rhEPO and cEPO in models of kidney I/R injury
From: Erythropoietin in the critically ill: do we ask the right questions?
Species | Model | Dose (IU·kg-1) | Protocol | Outcome | Histology | Apoptosis | Reference |
|---|---|---|---|---|---|---|---|
Rat | Bilateral renal artery occlusion | 300 | 30 minutes before ischemia, or 5 minutes before, or 30 minutes after start of reperfusion | Less rise in creatinine (150 to 170 versus 220 μmol·L-1) and higher creatinine clearance (0.3 versus <0.1 ml·minute-1); | 50% lower histopathology score | Less TUNEL cells (50%), less caspase-3 expression | [22] |
Mouse | Bilateral renal artery occlusion | 1,000 | Daily over 3 days or immediately before ischemia | Less rise in urea and creatinine (pre-treatment: 200 versus 350/0.8 versus 2.0 mg·dL-1; pre-reperfusion: 300 versus 350/1.5 versus 2.0 mg·dL-1mg·dL-1); attenuated tissue inflammation and lipid peroxidation | Reduced tubular dilatation, swelling and necrosis | ND | [23] |
Rat | Unilateral renal artery occlusion | 5,000 | 30 minutes before ischemia | Lower serum creatinine (0.04 versus 0.21 mmol·L-1) and urea (13 versus 41 mmol·L-1); enhanced tubular regeneration | Ameliorated tubular cast formation | Less ascending limb apoptosis (2.2 versus 6.5%) | [24] |
Rat | Bilateral renal artery occlusion | 500 | 20 minutes before ischemia | Less rise in blood urea (381 versus 193 mg·dL-1) and creatinine (6.7 versus 2.3 mg·dL-1); attenuated NFκB p65 | 50% reduction of tubular necrosis | Less TUNEL positive cells, less Bax expression | [25] |
Rat | Bilateral renal artery occlusion | 5,000 | At time of ischemia (T0), or 6 h post- ischemia (T6) | Less rise in serum creatinine (T(0): 0.04 versus 0.17, T(6): 0.03 versus 0.17 mmol·L-1); 2- to 3-fold higher mitosis in cortex and outer medulla | Reduced tubular luminal casts, no attenuation of necrosis | 50 to 70% less TUNEL cells | [26] |
Swine | Renal artery occlusion after nephrectomy | 1,000 | At time of ischemia, daily over 5 days of reperfusion | Ameliorated creatinine clearance at 12 h: 95 versus 68/74% at 12 and 36 h | Less necrotic cells | Less caspase-3 positive tubular cells | [38] |
Swine | Aortic balloon occlusion | 300 | 30 minutes before occlusion, over for 4 h during reperfusion | Improved creatinine clearance (66 versus 48ml·minute-1) and lower fractional Na excretion (8 versus 12%) | Histology not different | TUNEL not different | [39] |
Swine | Unilateral renal artery occlusion | 5,000 | 1 h before clamping | Less (25 versus 75%) fall in glomerular filtration rate, no difference in fractional Na excretion | ND | No difference in caspase-3 | [41] |
Primate | Unilateral renal artery occlusion | 2,400 | 5 minutes each before clamping and declamping | Lower creatinine, urea, and cystatin C (7 versus 3, 60 versus 40, 1.8 versus 2.5 mg·dL-1); lower IL-6 levels (50 versus 100 pg·L-1) | Ameliorated congestion, cell in filtration | Less tubular TUNEL cells | [42] |