Table 1.

Summary of preclinical EPO efficacy studies in AKI

ModelSpeciesSexNo. (per group)EPO DoseIndication (Timing)AssaysPredefined End PointsOutcomeRandomizedBlindingReporting DeathsPower AnalysisRef.
CisplatinumRatMales8100 units/kgPre + daily 9 daysGFR: day 4/9NonePositiveNoNoNoNo72
CisplatinumRatMales30100 units/kgPrevention: ×1 doseGFR: day 4NonePositiveYesNoNoNo73
CisplatinumRatMales55000 units/kgPrevention: ×2 dosesCreat: days 2–10NonePositive: only days 4/6YesNoNoNo74
CisplatinumMouseFemales81000 units/kgPrevention: ×3 dosesBUN: day 3NonePositiveNoNoNoNo75
CisplatinumRatsMales10100 units/kgTreatment: from day 4GFR: day 10NonePositiveNoNoNoNo76
CisplatinumRatsMales1225 μg/kg (DP)Prevention: ×1 doseBUN/histology: day 3NonePositiveNoNoNoNo77
CisplatinumRatsMales63000 units/kgPre/peri/post (day 5)Creat/BUN: day 6NonePositive: pre > peri and postNoNoNoNo78
CisplatinumRatsMales165000 units/kgPre/peri/post (day 2)Creat/BUN: day 4NonePositiveNoNoNoNo79
Cisplatinum rpt dosingRatsMales20100 units/kgPre + daily 2 wkCreat/BUN/death: 14 dNonePositive: no effect on deathYesNoYesNo63
CisplatinumRatsMale versus female5–6100 units/kgPrevention: ×3 dosesCreat/BUN/histology: day 7NonePositive in males not femalesNoNoNoNo71
Peri + post: ×7 dosesPositive in males not females
IR-AKIRatsMales83000 units/kgPrevention: ×1 doseCreat/histology: days 1–3NonePositive: day 1 onlyNoNoNoNo80
IR-AKIRatsMales12300 units/kgPre/peri/post (30 min)GFR: 6 hNonePositive: only pre and periNoNoNoNo81
IR-AKIRatsMales7500 units/kgPrevention: ×1 doseBUN/Creat: day 2NonePositiveNoNoYesNo62
IR-AKIRatsMales45000 units/kgPre/peri/post (6 h)Creat/histology: days 1–7NonePositiveNoNoNoNo82
IR-AKI + BMTRatsFemales?5000 units/kgPrevention: ×1 doseGFR: 14 and 28 dNonePositiveNoNoNoNo83
IR-AKIRatsMales8+10300 units/kgPrevention: ×1 doseCreat: day 3NoneNegative (compare PHD-I)NoNoNoNo65
IR-AKIRatsMales?500 units/kgPre + daily 3 dCreat/BUN/histology: day 3NonePositiveNoNoNoNo84
IR-AKIRatsMales45000 units/kgPrevention: ×1 doseCreat/fibrosis: days 4–28NonePositive: Creat; negative: fibrosisNoNoNoNo85
IR-AKIRatsMales61000 units/kgPrevention: ×1 doseCreat/histology: days 1+2NonePositiveYesNoNoNo86
IR-AKIRatsMales305000 units/kgPrevention: ×1 doseCreat/Ngal: day 3NonePositiveYesNoNoNo87
IR-AKIMacaquesMales1012, 000 unitsPrevention: ×1 doseCreat: days 1–7NonePositive: days 3 and 5NoNoYesNo61
IR-AKIPigsFemales95000 units/kgPrevention: ×1 doseGFR: 5 hGFRPositiveYesYesNoYes88
Aortic occlusionPig/LDLR mutMales and females65000 units/kgPrevention: ×1 doseCreat/NGAL: 8 hNoneNegativeYesNoNoNo89
CPBRatsMales103000 units/kgPrevention: ×1 doseBUN/Creat: day 1NonePositiveYesNoNoNo90
CPBRatsMales6500–5000 units/kgPrevention: ×1 doseCreat/cystatin C/UP: days 1–3NonePositive (dose response)NoNoNoNo67
Perinatal asphyxiaRatsMales and females152.5 mgPost approximately 15 min: ×1 doseHistology: day 7NonePositiveNoNoNoNo91
iv ContrastRatsMales113000 units/kgPrevention: ×2 dosesCreat/GFR/histology: day 1NonePositiveNoNoNoNo92
Hemorrhagic shockRatsMales9+10300 units/kgPrevention: ×1 doseBUN/Creat: 4 hNonePositiveNoNoNoNo64
Sepsis-LPS10+7Negative
Sepsis-LPSMiceMales64000 units/kgPrevention: ×1 doseCreat: 16 hPositiveNoNoNoNo93
Sepsis-CLPRatsMales5+7Prevention: ×1 dosePositiveNoNoYesNo60
104000 units/kgPerisurgery: ×1 doseGFR/histology/survival: day 2NonePositive
4Post (4 h): ×1 dosePositive
Sepsis-LPSRatsMales73000 units/kgPrevention: ×1 doseBUN/Creat: day 1NonePositiveNoNoNoNo94
Sepsis-LPSMiceMales9+201000 units/kgPost (1 h): ×1 doseBUN/Creat: day 1NonePositiveNoNoNoNo95
Sepsis-CLP10+20Positive
Sepsis-LPSMiceMales63000 units/kgPrevention: ×1 doseBUN/Creat: day 1NonePositiveNoNoNoNo96
AmikacinRatsFemales72000 units/kgPrevention: ×1 doseBUN/Creat/histology: day 1NonePositive: BUN/histology, not CreatNoNoNoNo97
Extreme exerciseRatsMales8?Prevention: ×1 doseBUN/Creat: day 1NonePositiveNoNoNoNo98
Rhabdo-IM glycerolRatsMales8300 units/kgPost (10 min): ×1BUN/Creat/histology: day 1NonePositive, but CPK lowerNoNoNoNo99
  • The PubMed search “Acute Kidney Injury AND (EPO OR Erythropoietin)” identified 128 references, of which 36 were preclinical AKI studies. rpt, repeat; BMT, bone marrow transplant; CPB, cardiopulmonary bypass; CLP, cecal ligation and puncture; IM, intramuscular; LDLR mut, low density lipoprotein receptor mutation; NGAL, neutrophil gelatinase-associated lipocalin; UP, urine protein; PHD-I, prolyl hydroxylation domain inhibitor; CPK, creatine phosphokinase.