Chapter

30

Acute Kidney Injury

Asif A. Sharfu ddin, Steven D. Weisbord, Pau l M. Palevsky, and Bru e A. Molitoris

Definition of A ute !idney "n#ury, )0** "n iden e of A ute !idney "n#ury, )0*+ .tiolo&ies of A ute !idney "n#ur y, )0*+ Prerenal A ute !idney "n#ury, )0*1 "ntrinsi A ute !idney "n#ury, )0*4 Postrenal A ute !idney "n#ury, )0-3

A ute !idney "n#ury $ollo%in& A ute !idney "n#ury after Solid A ute !idney "n#ury Asso iated %ith A ute !idney "n#ury Asso iated %ith A ute !idney "n#ury and 'ephroti Co,pli ations of A ute !idney
"n#ury, )0+3 Syndro,e, )0+3 7iver Disease, )0+3 Pul,onary Disease, )0+3 /r&an or Bone Marro% 2ransplantation, )0+3 Cardia Sur&ery, )0+)

'utritional and (astrointestinal

Co,pli ations, )0+"nfe tious Co,pli ations, )0+"n#ury, )0+-

/ther Se0uelae of A ute !idney Co,pli ations durin& 5e overy fro,

A ute !idney "n#ury, )0+-

.valuation of A ute !idney "n#ury, )08* Clini al Assess,ent of the Patient, )08*

Pathophysiolo&y of A ute !idney "n#ur y, )0-3 .6peri,ental Models, )0-3 A ute 2ubular 'e rosis, )0-9rine Assess,ent, )088 7aboratory .valuation, )081 5adiolo&i .valuation, )084 5enal Biopsy, )084 of A ute Differential Dia&nosis

Prevention and Mana&e,ent of A ute

!idney "n#ury, )0+8 Prerenal A ute !idney "n#ury, )0+8 "ntrinsi A ute !idney "n#ury, )0++ Postrenal A ute !idney "n#ury, )01) A ute !idney "n#ury, )01) !idney "n#ury, )013

Co,pli ations of Potassiu, Co,pli ations of A id;Base Co,pli ations of Mineral and 9ri A id <olu,e /verload and Cardia
:o,eostasis, )0+* :o,eostasis, )0+* :o,eostasis, )0+3

'ondialyti Supportive Mana&e,ent of 5enal 5epla e,ent 2herapy in A ute

/ut o,es of A ute !idney

"n#ur y, )01-

!idney "n#ury in Spe ifi Clini al Settin&s, )084

A ute !idney "n#ury in the Settin& of

Can er, )084 A ute !idney "n#ury in Pre&nan y, )0+)

Co,pli ations, )0+:e,atolo&i Co,pli ations, )0+-

2his han&e refle ts the re o&nition of serious short o,in&s in the older ter,inolo&y. 2he ter, a ute renal failure su&; A ute kidney in#ury ?A!"@ is a hetero&enous syndro,e defined &ested a di hoto,ous relationship bet%een nor,al kidney by a rapid ?over hours to days@ de line in the &lo,erular filtra; fun tion and overt or&an failure= in ontrast, the ter, a ute tion rate ?($5@ resultin& in the retention of ,etaboli %aste kidney in#ury atte,pts to apture the &ro%in& body of data produ ts, in ludin& urea and reatinine, and dysre&ulationasso iatin& s,all a ute and transient de re,ents in kidney of fluid, ele trolyte, and a id;base ho,eostasis.) Althou&h fun tion %ith serious adverse out o,es. Althou&h the ne%er often onsidered a dis rete syndro,e, A!" represents a broad ter,inolo& y does e,phasi>e the &raded aspe t of a ute kid; onstellation of pathophysiolo&i pro esses of varied severityney disease, it should be re o&ni>ed that this ter,inolo&y is and etiolo&y. 2hese in lude de reases in ($5 as a result of also i,perfe t. ",pli it in the %ord in#ury is the presen e of he,odyna,i perturbations that disrupt nor,al renal perfu; paren hy,al or&an da,a&e, %hi h ,ay be absent in a variety sion %ithout ausin& paren hy,al in#ury= partial or o,plete of settin&s asso iated %ith an a ute de line in kidney fun ; obstru tion to urinary flo%= and a spe tru, of pro esses %ith tion, su h as early obstru tive disease and prerenal a>ote,ia hara teristi patterns of &lo,erular, interstitial, tubular, or related to volu,e depletion. Althou&h the ter, a ute kidney /ver the past de ade, the ter, a ute kidney in#ury has vas ular paren hy,al in#ury. dysfun tion ,i&ht better hara teri>e the entire spe tru, of lar&ely supplanted the older ter, a ute renal failure ?A5$@. the syndro,e, a ute kidney in#ury is the ter, that has been adopted by onsensus and is no% in reasin&ly used in the )0**

Definition of A ute !idney "n#ury

Chapter 30 A ute !idney "n#ury

)0*-

,edi al literature. "n this hapter, the ter, A!" %ill be used TABLE 30-1 Causes of Prerenal Acute Kidney Injury to des ribe the entire spe tru, of the syndro,e, %hereas Intravascular Volu e !e"letion ARF will be restricted to situations of organ failure requiring :e,orrha&eAtrau,a, sur&ery, postpartu,, &astrointestinal renal replacement therapy. Although in clinical practice the (astrointestinal lossesAdiarrhea, vo,itin&, naso&astri tube loss term acute tubular necrosis (ATN) is often used synonymously 5enal lossesAdiureti use, os,oti diuresis, diabetes insipidus with AK ! these terms should not be used interchangeably. Skin and ,u ous ,e,brane lossesAburns, hyperther,ia Although ATN is the most common form of intrinsic AK ! 'ephroti syndro,e particularly in critically ill patients! it represents only one of Cirrhosis multiple causes of AK . Cardiac $ut"ut De reased urine output is often a ardinal ,anifestation #educed Capillary leak of A!", and patients are fre0uently lassified based on urine Cardio&eni sho k flo% rates as nonoli&uri ?urine output B*00 ,7Cday@, oli&u; Peri ardial diseasesArestri tive, onstri tive, ta,ponade ri ?urine output D*00 ,7Cday@, or anuri ?urine output D)00 Con&estive heart failure ,7Cday@.3 2ransient oli&uria ,ay o ur in the absen e of <alvular diseases si&nifi ant de re,ents in kidney fun tion, be ause in reased Pul,onary diseasesApul,onary hypertension, pul,onary e,bolis, %yste ic Vasodilation tubular salt and %ater reabsorption is a nor,al physiolo&i Sepsis Sepsis response to volu,e depletion. "n ontradistin tion, persistent Cirrhosis oli&uria despite the presen e of ade0uate intravas ular volu,e Anaphyla6is is virtually al%ays a ,anifestation of A!", %ith lo%er levels Dru&s Vasoconstriction of urine output typi ally asso iated %ith ,ore severe initial#enal .arly sepsis renal in#ury. 2he ate&ori>ation of A!" based on urine volu,e :epatorenal syndro,e has lini al i,pli ations for the develop,ent of volu,e over; A ute hyper al e,ia load, severity of ele trolyte disturban es, and overall pro&no; Dru&sAnorepinephrine, vasopressin, nonsteroidal antiinfla,,atory sis= &reater ,ortality risk is asso iated %ith oli&uri than %ith dru&s, an&iotensin; onvertin& en>y,e inhibitors, al ineurin inhibitors nonoli&uri A!".3 :o%ever, therapeuti interventions to au&; Increased inal Pressure ontrast a&ents A!" an develop denot novo in the settin& of inta kidney"odinated Intraa&do ,ent urine output have been sho%n to i,prove outt o,es. Abdo,inal o,part,ent syndro,e fun tion or an be superi,posed on underlyin& C!D ?a ute on hroni kidney in#ury@. "n fa t, the presen e of underly; in& renal i,pair,ent has been sho%n to be one of the ,ost seru, reatinine on entration %ith or %ithout asso iated de re,ents in urine output. 2his la k of standardi>ation has i,portant risk fa tors for the develop,ent of A!".*,- Mul; tiple ,e hanis,s ,ay ontribute to this in reased sus epti; ,ade it diffi ult to o,pare findin&s a ross epide,iolo&i bility, in ludin& di,inished renal fun tional reserve, i,pairedstudies and has led to a series of atte,pts to for,ulate a on; definition. salt and %ater onservation predisposin& to intravas ular vol; sensus "n 3003, the A ute Dialysis Euality "nitiative ?ADE"@ u,e ontra tion, de reased a tivity of deto6ifi ation ,e ha; (roup proposed the first onsensus definition of A!". 2he nis,s in reasin& sus eptibility to ytoto6i in#ury, i,paired ADE" %ork &roup proposed a lassifi ation s he,e %ith three learan e of potential nephroto6ins in reasin& the risk andC strata based on the ,a&nitude of the in rease in seru, reati; or duration of e6posure, and asso iated ,a rovas ular and is ular usually divided into three broad pathophysiolo&i ,i A!" rovas disease in reasin& the risk of is he,i in#ury. nine level andCor the duration of oli&uria. Con eptually, the first stratu, %ould provide the &reatest sensitivity for dia&; ate&ories based on auseF nosin& A!", %hereas the hi&her strata %ould provide in reas; ). Prerenal A!"Adiseases hara teri>ed by effe tive hypo; perfusion of the kidneys in %hi h there is no paren hy,al in& spe ifi ity of dia&nosis. 2hese three strata %ere o,bined %ith t%o out o,e sta&es defined by the need for and duration da,a&e to the kidney ?2able 30;)@ 3. "ntrinsi A!"Adiseases involvin& the renal paren hy,a of renal repla e,ent therapy, %hi h resulted in the five;tiered ?2able 30;3@ 5"$7. lassifi ation ?5isk of renal dysfun tion, "n#ury to the 3. Postrenal ?obstru tive@ A!"Adiseases asso iated %ith kidney, and $ailure of kidney fun tion, as %ell as the t%o out; a ute obstru tion of the urinary tra t ?2able 30;3@ o,e sta&es, 7oss of kidney fun tion and .nd;sta&e kidney Althou&h these ate&ories are useful for dida ti purposes disease@.8 More re ently, the A ute !idney "n#ury 'et%ork and help to infor, the initial lini al assess,ent of patients ?A!"'@ proposed a ,odifi ation of the 5"$7. lassifi ation %ith A!", there is often a de&ree of overlap bet%een these at; that in ludes the 5isk, "n#ury, and $ailure riteria %ith the e&ories. $or e6a,ple, renal hypoperfusion ,ay ause a spe ; addition of a 0.3 ,&Cd7 or hi&her rease in the seru, re; Althou&h the 5"$7. andin A!"' riteria have introdu ed tru, of renal in#ury ran&in& fro, prerenal a>ote,ia to overt atinine level tounifor,ity the riterion to that lini define 5isk ?2able 30;*@.+ a de&ree of al studies of A!", several li,i; A2' dependin& on its severity and duration. As a result, pre; tations to both of these sets of riteria have been re o&ni>ed. ise ate&ori>ation of the ause of A!" into one of these three $irst, althou&h validation studies have de,onstrated that A!" &roups ,ay not al%ays be possible, and transitions bet%een sta&e orrelates %ith in reasin& ,ortality risk, it is not lear etiolo&i ate&ories o ur. operational definition of A!" 2he absen e of ,ay a unifor, that this is the appropriate ,etri for assessin& the validity of has i,peded studies of its epide,iolo&y and ha,pered lini; the riteria. Se ond, on ordan e bet%een the seru, reati; al evaluations of preventative and therapeuti interventions. nine level and urine output riterion has not been established, A revie% of the literature de,onstrates a plethora of defini; even %ith re&ard to ,ortality risk. 2hird, there is poor or; tions based on varyin& absolute andCor relative han&es in the relation bet%een A!" sta&e and ($5. Sin e the ,a&nitude of

)0*8

Se tion < Disorders of !idney Stru ture and $un tion

TABLE 30-' (ajor Causes of Intrinsic Acute Kidney Injury Tu&ular Injur y "s he,ia due to hypoperfusion .ndo&enous to6ins .6o&enous to6ins :ypovole,ia, sepsis, he,orrha&e, irrhosis, on&estive heart failure= see 2able 30;) Myo&lobin, he,o&lobin, paraproteine,ia, uri a id= see 2able 30;Antibioti s, he,otherapy a&ents, radio ontrast a&ents, phosphate preparations Tu&ulointerstitial Injur y A ute aller&i 'onsteroidal antiinfla,,atory dru&s, antibioti s interstitial nephritis <iral, ba terial, and fun&al infe tions "nfe tions 7y,pho,a, leuke,ia, sar oid "nfiltration Allo&raft re#eInjury tion 1lo erular "nfla,,ation AntiI&lo,erular base,ent ,e,brane disease, antineutrophil ytoplas,i autoantibody disease, infe tion, ryo&lobuline,ia, ,e,branoprolif; erative &lo,erulonephritis, ",,uno&lobulin :e,atolo&i A nephropathy, syste,i lupus erythe,atosus, disorders :eno h;S hJnlein purpura, polyarteritis nodosa :e,olyti ure,i syndro,e, thro,boti thro,; #enal (icrovasculature bo ytopenihypertension, purpura, dru&s Mali&nant to6e,ia of pre&nan y, hyper al e,ia, radio ontrast a&ents, s lero; der,a, dru&s Lar0e Vessels Arteries 2hro,bosis, vas ulitis, disse tion, thro,boe,; bolis,, atheroe,bolis,, trau,a <eins 2hro,bosis, o,pression, trau,a

TABLE 30-) #I*LE and Acute Kidney Injury +et,or- .AKI+/

!efinition and %ta0in0 of Acute Kidney Injury

Def in it i on

5"$7. An in rease in seru, reatinine of G-0H developin& over D+ days or A urine output of D0.- ,7Ck&Chr for B8 hr "'C5.AS. 5"$7. "' S.59M S2A(. C5.A2"'"'. Ris" #$%& '%.$ m()

A!"' An in rease in seru, reatinine of G0.3 ,&Cd7 or G-0H developin& over D*1 hr or A urine output of D0.- ,7Ck&Chr for B8 hr

Sta &i n& Cri t er i a

n*ury #+%%& '%.$ m()

Failure #,%%& '%.$ m()

TABLE 30-3 Causes of Postrenal Acute Kidney Injury

failure ?$i&ure 30;)@. 5elian e solely on han&es in seru, re; han&e in seru, reatinine on entration is ti,e dependent, atinine level andCor urine output to dia&nose A!"1 has resulted a patient %ith a ($5 that is essentially >ero ,ay only fulfillin the inability to identify the in ipient sta&es of intrinsi the 5"$7. sta&e 5 or A!"' sta&e ) riteria, but ,ay later kidney in#ury, %hi h ,ay be the ,ost opportune ti,e for ,eet the riteria for 5"$7. sta&e $ or A!"' sta&e 3 despite phar,a olo&i intervention. 2o fa ilitate the early dia&nosis an in reasin& ($5. $ourth, the definition of A!" by seru, of intrinsi in#ury, ,ultiple bio,arkers of tubular in#ury have reatinine riteria in both s he,es relies on a referent baseline been evaluated.4,)0 Bio,arkers for A!" in lude ';a etyl;K;D; seru, reatinine level, %hi h is often unavailable. <ariations &lu osa,inidase ?'A(@, kidney ,ole ule ) ?!"M;)@, neutrophil &elatinaseIasso iated in#ury lipo alin ?'(A7@, and in the definitions used for this referent value an alter the las; interleukin )1 ?"7;)1@, a,on& others.4,)0 "n addition, seru, sifi ation of patients. $ifth, both the 5"$7. and A!"' las; ystatin C has been proposed as ,ore sensitive than seru, sifi ations e,ploy relative han&es in seru, reatinine level to

2""er 2rinar y Tract E3trinsic Causes 5etroperitoneal spa eAly,ph nodes, tu,ors Pelvi or intraabdo,inal tu,orsA ervi6, uterus, ovary, prostate $ibrosisAradiation, dru&s, infla,,atory onditions sta&e A!". Analysis of reatinine kineti s de,onstrates that 9reteral li&ation or sur&i al trau,a the ti,e re0uired to attain a fi6ed per enta&e han&e in seru, (ranulo,atosis diseases reatinine on entration in the settin& of severe A!" depends Lo,er 2rinary Tract Causes :e,ato,a upon the baseline level of kidney fun tion, %hereas the ini; ProstateAbeni&n prostati hypertrophy, ar ino,a, infe tion tial rate of han&e in seru, reatinine level is relatively inde; BladderAne k obstru tion, al uli, ar ino,a, infe tion ?s histoso,iasis@ pendent of kidney fun tion. 2hus, early in the ourse of A!", $un tionalAneuro&eni bladder se ondary to spinal ord in#ury, absolute han&es in seru, reatinine level ,ay be dete ted diabetes, ,ultiple s lerosis, stroke, phar,a olo&i side effe ts of dru&s ,ore readily than relative han&es. $inally, it ,ust be re,e,; ?anti holiner&i s, antidepressants@ bered that these lassifi ation syste,s are independent of the 9rethralAposterior urethral valves, stri tures, trau,a, infe tions, tuber; various auses of A!" ?i.e., prerenal, intrinsi , obstru tive@. 2""er 2rinar y Tract Intrinsic Causes ulosis, tu,ors 'ephrolithiasis Despite these short o,in&s, the use of standardi>ed lassifi; Stri tures ation s he,es has enhan ed interpretation of epide,iolo&i Con and eptually, A!" o,prises a spe tru, of stru tural and .de,a studies desi&n of lini al trials. fun tional kidney disease in %hi h there ,ay be an evolution Debris, blood lots, slou&hed papillae, fun&al ball fro, in#ury to or&an dysfun tion and finally to overt or&an Mali&nan y

(oss Need for renal repla e,ent therapy for B* %k -nd 'eed for renal stage repla e,ent therapy for B3 ,o

95"'. "'C5.AS. A!"' /92P92 "' S.59M S2A(. C5"2.5"A C5.A2"'"'. G0.3 ,&Cd7= Sta&e ) k&Chr for or G-0H B8 hr G)00H Sta&e 3 k&Chr for B)3 hr G300H Sta&e 3 k&Chr for B3* hr or anuria for B)3 hr

)0*1

Se tion < Disorders of !idney Stru ture and $un tion

Chapter 30 A ute !idney "n#ury

)0*+

of hypovole,ia, adrener&i a tivity independently onstri ts the afferent arteriole as %ell as han&in& the efferent arte; Prerenal a>ote,ia is the ,ost o,,on ause of A!" and riolar resistan e throu&h an&iotensin "". a;Adrener&i a tiv; a ounts for about *0H to --H of all ases.)3,)-,3) "t results ity pri,arily influen es kidney vas ular,odel resistan %hereas $"(95. 30;) Con eptual depi e, tin& sta&es fro, kidney hypoperfusion o%in& to a redu ed effe tive arte; renal nerve a tivity is linked to renin release throu&h !idney "n reased 'or,al ($5 Death in the develop,ent of ?left to ri&ht@ and re overy Da,a&e K;adrener&i re eptors on renin; ontainin& ells. "n ontrast,fro, failure rial blood volu,e. .ffe risk tive arterial blood volu,e is the vol; ?ri&ht to left@ a ute kidney in#ury ?A!"@. ?$ro, Murray u,e of blood effe tively perfusin& the body or&ans. Co,,ona3;adrener&i a&onists pri,arily de rease the &lo,erular P2, Devara#an P, 7evey AS, et alF A fra,e%ork and key onditions ausin& hypovole,ia;,ediated redu ed effe tive ultrafiltration oeffi ient via an&iotensin "". Althou&h vaso; resear h 0uestions in A!" dia&nosis and sta&in& in dif; arterial blood volu,e in lude he,orrha&e ?trau,ati , &astro; dilation ,i&ht be e6pe ted as a result of a ute re,oval of Ante edents ferent environ,ents, Clin L A, So 'ephrol 3F18-, 3001, intestinal, sur&i al@, &astrointestinal losses ?vo,itin&, diarrhea, adrener&i a tivity, a transient in rease in an&iotensin "" is "nter,ediate sta&e $i&ure ).@ naso&astri su tion@, renal losses ?overdiuresis, diabetes insipi; a tually seen, alon& %ith onstan y in ($5 and renal blood A!" dus@, and third spa in& ?pan reatitis, hypoalbu,ine,ia@. "n flo%. .ven after suba ute renal denervation, renal vas ular /ut o,es addition, ardio&eni sho k, septi sho k, irrhosis, hypoalbu; sensitivity to an&iotensin "" in reases as a result of ,a#or ,ine,ia, and anaphyla6is all are pathophysiolo&i onditionsupre&ulation of an&iotensin "" re eptors. :en e, o,ple6 reatinine for dete han&es in ($5, and urinary ys; that de rease effe tive tin& arterial ir ulatin& volu,e, indepen; effe tsof on renin;an&iotensin tivity o ur %ithin kidney patient populations a and variability in the the riteria for the ini; tatin C has been proposed as a ,arker of tubular in#ury.4,)),)3 dent of total body volu,e status, and result in redu ed kid; se ondary to of in renal reased renal adrener&i a tivity durin& prer; ,ul; tiation repla e,ent therapy. "n a ,ultinational, All of these syste,s %ork to&ether and sti,ulate vaso; none of these bio,arkers has yet been if ade0uately ney Althou&h blood flo%. Prerenal a>ote,ia reverses rapidly kidney enal a>ote,ia.31 ti enter observational study of 34,384 riti ally ill patients, onstri validated for routine lini al use, they have the potential to tion in ,us ulo utaneous and splan hni ir ula; perfusion is restored, be ause by definition the inte&rity of the -.+H developed severe A!"thro and *.3H eived renal repla e; inhibit salt loss u&hres%eat, and sti,ulate thirst, provide an early dia&nosisinta of intrinsi A!", to differentiate renal paren hy,a has re,ained t. :o%ever, severe and tions, ,ent therapy.)1 Many epide,iolo&i studies of A!" have relied on data thereby ausin& retention of salt and %ater to ,aintain blood volu,e;responsive ?prerenal@ A!" prolon&ed hypoperfusion ,ay result in fro, tissue intrinsi is he,ia disease, lead; fro, lar&e ad,inistrative databases. 2hese data need to be pressure and preserve ardia output and erebral perfusion. and to provide pro&nosti infor,ation re&ardin& lini al in& to A2'. 2herefore, prerenal a>ote,ia and is he,i the A2' interpreted %ith aution, ho%ever, be ause ad,inistrative there are various o,pensatory ,e ha; ourse of an episode of A!". /ne or ,ore of these bio,arkers arePrerenal part of aa>ote,ia ontinuous tru, of divided ,anifestations of renalCon o,itantly, hasspe also been into volu,e odin& for A!" is in o,plete and ,ay only apture 30H to nis,s to preserve &lo,erular perfusio n.34 Autore&ulation ,ay provide a ,eansnonresponsive by %hi h patients an 2he be identified at the hypoperfusion. responsive and volu,e types. for,er is 30H of all episodes of A!". "dentifi ation of A!" is a hieved by stret h re eptors in afferent arterio lesre0uirin& that sta&e of but A!" to latter &uideis the i,ple,entation of spe easyintoipient o,prehend, the less strai&htfor%ard. "n ifi renal repla e,ent therapy usin& ad,inistrative data is sub; ause vasodilation in response to redu ed perfusion pressure. therapy to a,eliorate kidney da,a&e or pro,ote re volu,e overy of volu,e;nonresponsive for,s, additional intravenous stantially ,ore onditions o,plete. "n an analysis %orks of data fro, 9nder physiolo&i autore&ulation until a the kidney fun tion. is of no help in restorin& kidney perfusion and fun tion. Dis; 'ational har&e Survey ,ean syste,i:ospital arterial Dis blood pressure of in +-the to 9nited 10 ,, States, :& ease pro esses su h as on&estive heart failure and sepsis ,ay thehed. Centers for Disease Control and Prevention observed "n iden e of A ute !idney "n#ury is rea Belo% this, the &lo,erular ultrafiltration pres;an not respond to intravenous fluids be ause ,arkedly redu ed in rease in hospital dis har&es %ith a dia&nosis of A!" fro, sure and (5$ de line abruptly. 5enal produ tion of pros; ardia or total vas eular resistan respe tively, )1 per kallikrein, )00,000 population inas)410 38- per )00,000 2heoutput pre ise in iden of A!" has e, been diffi ult prevent to esti,ate ta&landins, and kinins, %ell to as nitri o6ide, is in i,proved kidney fun tion ?see 2able 30;)@. 300-.)4 Si,ilar trends have observed in analyses of the :ypovole,ia rease in ,ean be ause of the auses absen a e, de until re ently, of a arterial standardpressure definition. in reased, %hi h ontributes to been the vasodilatio n.30,3) 'on; 9.S. 'ation%ide "npatient Sa,ple ?'"S@ and a -H sa,ple "t has been esti,ated that 3H to +H of hospitali>ed patients steroidal antiinfla,,atory dru&s ?'SA"Ds@, by inhibit; that a tivates barore eptors and initiates a as ade of neural 9.S. hospitali>ed Medi %orsen are benefi iaries. "n an analysis and 3-H to 30H patients in the intensive are unit ?"C9@ in& of prosta&landin produ tion, kidney perfusion in and hu,oral responses, %hi hof leads to a tivation of the sy,; that o,bined ad,inistrative and lini al data fro, a sin&le develop A!", %ith -H to 8H of the "C9 population re0uirin& patients %ith hypoperfusion. Sele tive efferent arterio lar patheti nervous syste, and in reases produ tion of ate hol; inte&rated health are delivery syste,, the in iden e of A!" renal repla e,ent therapy after developin& A!".)3;)8 :o%; onstri tion, a result of an&iotensin "", helps preserve the a,ines, espe ially norepinephrine. 2here is in reased release that did not re0uire the use of renal repla e,ent therapy %as ever, esti,ates of the in iden e of A!" are hi&hly dependent intra&lo,erular pressure and hen e ($5. An&io tensin o n; of antidiureti hor,one ,ediated both by hypovole,ia and found to in ?AC.@ rease fro, 333.+ to -33.* per )00,000 person; oninthe e,ployed, rates; a,on& hospitali>ed vertin& en>y,e inhibitors inhibit synthesis of an&io; by a rise e6tra definition ellular os,olality, resultin& in%ith vaso onstri years fro, )448 to 3003.30 /ver the sa,e period, A!" re0uir; patients ran&in& fro, as hi&h as **H %hen the definition is tensin "" and so disturb this deli ate balan e in patients %ith tion, %ater retention, and urea ba k diffusion into the papil; in& renal repla e,ent therapy in reased fro, )4.to 34.per based on a han&e in seru, reatinine level of at least 0.3 ,&C severe redu tions in effe tive arterial blood volu,e su h as lary interstitiu,. "n response to volu,e depletion or states of )00,000 person;years.30 A!" %as ,ore o,,on in ,en and d7 to as lo% as )H %hen the re0uired in rease is at least 3.0 severe on&estive heart failure o r bilateral renal artery ste; de reased effe tive arterial blood volu,e, there is in reased inand thethus elderly. "n a subse0uent analysis, ,&Cd7. "n a enter analysis at an urban tertiary are nosis an %orsen prerenal a>ote,ia. /npree6istin& the other kidney intrarenal an&iotensin "" asin&le; tivity via a tivation of the renin; disease %as de,onstrated to be an i,portant fa tor for hospital ondu ted in )448 that defined A!" as an in rease hand, very hi&h levels of an&iotensin "", as seen in irrisk ulatory an&iotensin;aldosterone syste,. An&iotensin "" is a very Althou&h these o,pensatory ,e hanis,s ,ini,i>e the levels the develop,ent of A!" re0uirin& dialysis. "n reasin& in seru, reatinine on entration of 0.,&Cd7 for patients sho k, ause onstri tion of both afferent and efferent arteri; potent vaso onstri tor, in reasin& pro6i,al tubule sodiu, pro&ression to%ard A!", they too are over o,e in states risk asso %ith baseline hroni of kid; %iththrou&h a baseline seru, level ofby ).4 ,&Cd7 or less, anof oles, %hi h%ere ne&ates itsiated prote tive,ore effe severe t. absorption a o,ple6 effe reatinine t in the &lo,erulus severe hypoperfusion. 5enovas ular disease, hypertensive ney disease ?C!D@. Co,pared %ith patients %ith a baseline in rease of ).0 ,&Cd7 for patients %ith a baseline seru, re; preferentially in reasin& efferent arteriolar resistan e. ($5 nephros lerosis, and ?e($5@ diabeti of nephropathy, as %ell as older a&e, esti,ated ($5 ,ore than 80 ,7C,inC).+3 ,3, atinine levelby ofthe 3.0 to *.4 in ,&Cd7, an in rease of ).- ,&C is preserved overall resultin& rease inand &lo,erular predispose patients to prerenal a>ote,ia33 at lesser de&rees of a those %ith e($5 values of *to -4 ,7C,inC).+3 ,3 had d7 for patients %ith a baseline seru, reatinine level &reater hydrostati pressure. Durin& severe volu,e depletion, an&io; hypotension.33 Prerenal a>ote,ia predisposes patients to is h; nearly t%ofold in reased risk of developin& dialysis;re0uirin& - ,&Cd7, A!" %as found to develop tensin than "" a tivity is even &reater, leadin& to afferent arterio; in +.3H of *833 e,i A2' or nephroto6i A!". Superi,position of events A!". 2his risk in reased to ,ore than *0;fold a,on& patients onse patients.)3 2his lar onstri tion utively that redu treated es renal plas,a flo%, ($5 , and rate the %as hi&her than the su h%ith as anesthesia and sur&ery are than kno%n result in fur; baseline e($5 valuesthat of less )- to ,7C,inC).+3 ,3. *.4H rate the investi&ators had observed in a si,ilar study in filtration fra tion, and ,arkedly au&,ents pro6i,al tubular ther de reases in renal blood flo% and that %ould notthe nor,ally 9nderlyin& diabetes ,ellitus, hypertension, and presen e )4+4.)+ 2he ,ost fre0uent type %as A!" aused by de reased sodiu, reabsorption in an effort to restore plas,a volu,e.33 result in kidney in#ury ,ay pre ipitate is he,i A2' in the of proteinuria %ere also asso iated %ith in reased risk of hos; renal perfusion, observed in 34H of episodes of A!", follo%ed An&iotensin "" has also been sho%n to have dire t effe ts on .tiolo&ies of A ute !idney "n#ury settin& of prerenal a>ote,ia. Si,ilarly, prerenal a>ote,ia also pital;a 0uired A!". by in,edi ation;asso iatedreA!" transport the pro6i,al tubule throu&h eptors ?)8H@, lo ated in radio ontrast a&entI predisposes patients to radio ontrast a&ent;indu ed A!" and indu ed also A!" ?))H@, postoperative A!" ?4H@, and sepsis;asso; the tubule. "t has been postulated that the pro6i,al tubule Althou&h in the lini al settin& A!" is 0uite often ,ultifa to; to other for,s of nephroto6i A!". 2herefore it is i,perative iated A!" ?8.-H@. /verall %as )4.*H, %ith hi&her an lo ally produ e an&iotensin "". :en e, ,ortality under onditions Althou&h definition is less of an issue %ith re&ard to rates rial, it should al%ays be approa hed dia&nosti ally by keepin& to dia&nose prerenal a>ote,ia pro,ptly and initiate effe tive ,ortality rates asso iated %ith in reased seru, rates re; of volu,e depletion, an&iotensin "" a sti,ulates a si&nifi lar&erin frareases ; 5enal of A!" sy,patheti re0uirin& nerve renal repla tivity&reater e,ent is therapy, antly in reported in ,ind the three ,a#or fun tional ausesF na,ely, prerenal, treat,ent, be ause it is a potentially reversible ondition that atinine on entration. tion of the transport, %hereas volu,e e6pansion blunts this in prerenal a>ote,ia. Studies have sho%n that inthe the settin& vary onsiderably be ause of differen es in hara teristi intrinsi , and postrenal. anslead to is he,i A2' or nephroto6i A!" if therapy is
Co,pli ations
response.33;3+

Prerenal A ute !idney "n#ury

delayed or its severity is in reased.