Erythropoietin (EPO) in acute kidney injury.docVIP

MooreandBellomoAnnalsofIntensiveCare2011,1:3 /content/1/1/3 REVIEW OpenAccess Erythropoietin(EPO)inacutekidneyinjury ElizabethMoore,RinaldoBellomo* Abstract Erythropoietin(EPO)isa30.4kDaglycoproteinproducedbythekidney,andismostlywell-knownforits physiologicalfunctioninregulatingredbloodcellproductioninthebonemarrow.Accumulatingevidence, however,suggeststhatEPOhasadditionalorganprotectiveeffects,whichmaybeusefulinthepreventionor treatmentofacutekidneyinjury.Theseprotectivemechanismsaremultifactorialinnatureandincludeinhibitionof apoptoticcelldeath,stimulationofcellularregeneration,inhibitionofdeleteriouspathways,andpromotionof recovery. Inthisarticle,wereviewthephysiologyofEPO,assesspreviousworkthatsupportstheroleofEPOasageneral tissueprotectiveagent,andexplainthemechanismsbywhichitmayachievethistissueprotectiveeffect.Wethen focusonexperimentalandclinicaldatathatsuggestthatEPOhasakidneyprotectiveeffect. Introduction andcontains upto 14 sialic acid residues. Its carbohy- Erythropoietin (EPO) is a complex molecule, which drate portion contributes 40% of its molecular weight regulates red blood cell production in the bone mar- [1]. The N-linked polysaccharide side chains appear to row. Recombinant human EPO (rHuEPO) is commer- beimportantforthebiosynthesisandsecretionofEPO, cially available and is widely used for the treatment of enhance its stability in blood, and limit hepatic clear- anemia. In recent years, additional nonerythropoietic ance, thusfacilitating thesystemic transit ofEPOfrom tissue/organ protective properties of EPO have kidneytobonemarrow[2]. become apparent, in particular for kidneys. In this Thevariablenatureofthesialicacidcontentgivesrise article, we consider the evidence supporting EPO as a toEPOisoformswithdifferencesincharge.Asthenum- general tissue protective drug and discuss the poten- berofsialicacidgroupsonthecarbohydrate portionof tial mechanisms by which it may achieve this general EPO increase, so does its serum half-life (T