Renal failure and its treatment

8 Pages·0.234 MB·English

by  Mishra M., Ng S., Hanison J.

NEPHROLOGY
Renal failure and its
Learning objectives
treatment
Afterreadingthisarticle,youshouldbeableto:
C classifyrenalfailure
MonalisaMishra
C understandthecausesofrenalfailure
SarahNg C understanditsprevalenceandoutcome
JamesHanison C classifythetreatment of renal failureincludingthedifferent
modalitiesofrenalreplacementtherapy
C understand the methods of anticoagulation used in renal
replacementtherapy
Abstract
Acutekidneyinjury(AKI)isacommoncomplicationofacuteillness.It
isassociatedwithsignicantmorbidityandmortalityaswellasahigh
cost to healthcare systems. There are a broad range of causes of Aetiology
AKI which should be considered in a systematic fashion to avoid ThereareabroadrangeofcausesofdevelopingAKI.Differential
missingmultiplepotentialcausativefactors.Theseincludepre-renal diagnosismustbeconsidered in asystematicfashion to avoid
causesfromhypovolaemia,intrinsicrenalcausessuchasglomerular missingmultiplefactorsthatmaybecontributingtothecondi-
diseases and post-renal obstructive causes. In the intensive care tion.Traditionally,AKIisdividedintopre-renal,renalandpost-
unit,two-thirdsofAKIcasesresultfromrenalhypoperfusion,sepsis, renal causes. Pre-renal causes include hypovolaemia or a
contrastandnephrotoxicagents;upto5%willrequirerenalreplace- decreasedeffectivearterialvolume.Intrinsicrenalcausescanbe
menttherapy.Modalitiesofrenalreplacementtherapyincludeinter- consideredunder differentanatomiccomponentsof thekidney
mittent haemodialysis, peritoneal dialysis and continuous (vascular supply; glomerular, tubular and interstitial disease).
haemoltration. Continuous haemoltration is usually favoured in the Post-renal obstructiverenal failureisusuallydiagnosedbyuri-
intensivecaresettingas ithas greaterhaemodynamic stabilityand nary tractdilation on renal ultrasound. In thehospital setting,
greatercapacitytoextractuidfrompatientswithfluidoverload.Anti- pre-renal andacutetubularnecrosis(ATN) accountforthema-
coagulationoptions canbeachieved withsystemic anticoagulation jorityof AKI cases. Thesearealsooftensuperimposedonpre-
suchasheparinorregionalanticoagulationwithcitrate. existing chronic kidney disease (CKD). In the intensive care
unit,two-thirdsofcasesofAKIarearesultofthecombinationof
Keywords Acuterenalfailure;haemoltration;haemodialysis;renal
impairedrenalperfusion,sepsisandnephrotoxicagents.
RoyalCollegeofAnaesthetistsCPDMatrix:1A01,2C04
Prevalenceandoutcome
UncomplicatedATNtypicallyrecoversin2e3weeks.Thiscould,
however, be complicated by superimposed renal insults. Epi-
Acutekidneyinjury
sodes of hypotension induced by haemodialysis may lead to
Currentdefinitionandclassification additionalischaemiclesionsanddelayrenalfunctionalrecovery,
Acutekidneyinjury(AKI)isaclinicalsyndromecharacterizedby especially in patients who have multiple comorbidities. It is
a sudden decline in glomerular fltration rate (GFR) causing becoming increasingly recognized that even lesser degrees of
decreasedeliminationof nitrogenouswasteproductsandurae- kidney injury have important implications for health as AKI
mic toxins. Kidney Disease: Improving Global Outcomes represents a heterogeneous clinical syndrome with multiple
(KDIGO)defnesAKI asanyofthefollowing:increaseinserum causesratherthanonedisease.
creatinineby(226.5mmol/lwithin48hours;increaseinserum TheincidenceofAKI inunselectedhospitalizedpatientshas
creatinineto1.5timesbaseline,whichisknownorpresumedto been estimated to be18%, and AKI accountsfor 1e4% of all
haveoccurredwithintheprior7days,orurinevolume<0.5ml/ hospitaladmissions.AKIhasthehighestincidenceamongthose
kg/h for 6 hours. AKI is staged for severity according to the aged65andolder.PatientswitheGFR<30ml/min/1.73m2have
criterialistedinTable1. a30-to40-foldhigherriskofdevelopingAKI.AKI isassociated
with high costs and adverse clinical outcomes, including
increasedmortality,lengthofstayanddevelopmentorprogres-
sionof CKD. Thecostof AKI totheNHSinEnglandwasesti-
MonalisaMishraMBBSMDFNBisaSeniorClinicalFellowinIntensive matedtobe£1.4billioneachyear.ThenumberofcasesofAKI
CareMedicineatManchesterUniversityNHSFoundationTrust, increasedfromover600,000in2001toover3millionin2011,
Manchester,UK.Conflictsofinterest:nonedeclared. although mortality has signifcantly decreased from 21.9% to
9.1%in2001.ThemortalityofAKIrangesfrom8.1%inpatients
SarahNgMBChBMRCP isaSpecialtyRegistrarinNephrologyand
IntensiveCareMedicineinHealthEducationNorthWest,UK. withAKI stage1e33% inpatientswithAKI stage3.
Conflictsofinterest:nonedeclared. Theincidences of CKD and end-stagerenal disease(ESRD)
afterAKI were25.6and8.6per100person-years, respectively.
JamesHanisonBScMBChBFRCAFFICMPGCertisaConsultantin
TheannualabsoluteriskfordevelopingESRDafteranepisodeof
AnaestheticsandIntensiveCareMedicineatManchesterUniversity
NHSFoundationTrust,Manchester,UK.Conflictsofinterest:none AKIrangesfrom0.6%to1.2%inthosewithmildAKIcompared
declared. to 9% in those with pre-existing CKD. Patients should be
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 398 Ó2021PublishedbyElsevierLtd.
NEPHROLOGY
StagingofAKI (KDIGOcompositestaging)
AcuteKidneyInjuryNetwork(AKIN)andRIFLEclassifcationsofAcuteKidneyInjury
AKINStaging Urineoutput RIFLE
SerumCreatinine Class SerumcreatinineorGFR
Stage1:Increaseofx1.5frombaseline <0.5ml/kg/hfor>6hr Risk Increaseinserumcreatininex1.5or
or 26.5mmol/l GFRdecrease>25%
Stage2:Increaseofx2frombaseline <0.5ml/kg/hfor>12hr Injury Serumcreatininex2orGFR
decreased>50%
Stage3:Increaseofx3frombaseline, <0.3ml/kg/hfor24hor Failure Serumcreatininex3,orserumcreatinine
or 354mmol/lwithanacuteincrease anuriafor12hr 354mmol/lwithanacuterise>44
ofatleast44mmol/loronRRT mmol/lorGFRdecreased>75%
Loss Persistentacuterenalfailure¼complete
lossofkidneyfunctionforlongerthan
4weeks
End-stagekidney ESRD>3months
disease
Table1
followedupat3monthsafterAKI forresolution, new-onsetor resuscitation in critically ill patients havebeen associated with
worseningofpre-existingCKD. worse renal outcomes and increased mortality. The Fluid and
Catheter Treatment Trial (FACTT) indicates that after initial
AKIintheintensivecareunit resuscitation, aconservativeapproach tofuidadministration is
AKIisanindependentriskfactorfordeathandupto40%ofICU associatedwithfaster weaningfrommechanical ventilationand
patients develop AKI. Up to 5% of ICU patients require renal decreasedICUlengthofstaywithoutanydeteriorationofkidney
replacementtherapy.Factorsthatexacerbateacutekidneyinjury functionorworseoutcomesinpatientswithacutelunginjury.The
includehypovolaemiaintheperioperativeperiod,repeatedexpo- VasopressinandSepticShockTrial(VASST)showedthatthebest
suretocontrastandnephrotoxicagentsandinfammatorystates. survival outcomesarewith apositivefuid balanceof approxi-
Mortality is attributed to infection, haemorrhage or persistent mately3litreswithin12hours.Therefore,aliberalfuidapproach
shockdespiteoptimalcare. appearstobebenefcial inthefrsthoursofshock,whileacon-
servativeapproachfollowingresolutionofshockispreferred.
AcutemanagementofAKI
KDIGO AKI guidelines recommend isotonic crystalloids
Primaryprevention andearlydiagnosisof AKI areessential in
insteadofcolloidsforintravascularexpansioninpatientsatrisk
improvingoutcomes and preventingresidual effects of kidney
ofAKI.Incriticallyillpatientsreceivingmechanicalventilation,
damage. All patientsshouldhavearisk assessmenttoidentify
respiratorychangesinleftventricularstrokevolumecanpredict
andreverseriskfactors.MajorriskfactorsforAKIincludethose
fuidresponsiveness.Inhypovolaemicpatients,positive-pressure
witholderage(>75years), diabetes, hypertension, sepsis, ma-
ventilation may induce a fall in venous return and lead to a
lignancy,surgicalpatientsandpre-existingcardiacdisease.
decreaseincardiacoutput.
AkeyfactorinpreventingAKIishaemodynamicstabilization
withoptimizationofcardiacoutputandbloodpressuretoensure Preventionofdrugandnephrotoxin-inducedacute
adequaterenal perfusion.Adequatevolumeexpansionisessen- kidneyinjury
tial indecreasingrisk of AKI intheperioperativeperiodinthe Riskfactorsfordevelopingnephrotoxicityincludeageolderthan60
initial phase,butthisneedstobebalancedwithpreventingthe years,pre-existingCKD,volumedepletion,diabetes,heartfailure,
undesirablesideeffects of fuid accumulation and overload. It andsepsis. Drugmonitoringof nephrotoxinsiscrucial in at-risk
canbeparticularlychallengingtomanagepatientswithsevere patients. Preventative measures include correctly estimating the
congestivecardiacfailureor diastolicdysfunction, whererenal GFRbeforeinitiationoftherapy,adjustingthedosageofpotential
perfusionisinadequatedespitenormalvolumestatus.Excessive nephrotoxins,andmonitoringrenalfunctionduringtherapy.
fuid replacement istolerated poorly in thispatient group and
mayprecipitatepulmonaryoedema. Contrast-inducednephropathy(CIN)
The International Guidelines for Sepsis Management by the AKI secondarytocontrastnephropathy(defnedasanincrease
SurvivingSepsiscampaignrecommendsinitialfuidresuscitation in creatinineof >44mmol/l) typically occursin patientswith
withcrystalloidsforaminimumof30ml/kgandaddingalbumin underlyingrenalimpairmentandisrarelyseeninpatientswith
in patients who continueto requiresubstantial amounts of cr- normalrenalfunction.Itmayoccurwithintravenousandintra-
ystalloid to maintain adequate mean arterial pressure (MAP). arterial contrast, but not with oral contrast. Theincidenceof
Fluidchallengeshouldbecontinuedfor aslongashaemodyna- CIN is 20% in patients with creatinine levels of more than
mic parameters continueto improve. Lateand aggressivefuid 176mmol/l and50% whenlevelsaremorethan440mmol/l.
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 399 Ó2021PublishedbyElsevierLtd.
NEPHROLOGY
Other risk factorsincludediabeticnephropathy, advancedage obstruction. Physical examination, especially assessment of
(older than 75years), congestiveheart failure, volumedeple- volumestatusisparticularlyhelpful.Trendsindailyintakeand
tion, andhighor repetitivedosesof radiocontrastagents. The outputvolumesassistindeterminingtheextracellularfuidvol-
KDIGOAKI guidelinesrecommend volumeexpansion with ei- ume of the critically ill patient. Abdominal examination can
therisotonicsodiumchlorideorsodiumbicarbonatesolutionsin reveal importantinformation, suchasadistendedbladder sug-
patientsatriskofCIN unlesstherearecontraindications.Mea- gesting lower urinary tract obstruction, or a tense distended
surestoreduceAKI risk shouldbeimplementedinthosewith abdomen which may point towards abdominal compartment
eGFR<45ml/min/1.73m2. syndrome.Intra-abdominalpressurecanbemeasuredintheICU
and a diagnosis of abdominal compartment syndrome made
TreatmentofAKI whenpressuresexceed20mmHg.
Inrecentyears,therehasbeenalotoffocusonimprovingtimely Fever,skinrashandarthralgiasmaypointtowardssingsofa
diagnosis and earlier recognition of AKI as it is becoming systemicdiseasesuchassystemiclupuserythematous,vasculitis,
increasinglyrecognizedthatserumcreatinineisarelativelylate endocarditis,oradrugallergywithacuteinterstitialnephritis.A
indicator of renal injury. Initial management of AKI includes leukocytoclasticrashonthelowerextremitiescouldbeHenoch-
thoroughassessmentof thecauseof renal dysfunctionandthe Schonleinpurpuraorcryoglobulinaemiainapatientwithhepa-
volaemic status. Nephrotoxic agents should be avoided and titisC.Inpatientswithrecentaorticcatheterization,itisimpor-
exposuretointravascularradiocontrastdyeneedstobecarefully tanttolookforlivedoreticularisoradiscolouredtoeastheycould
rationalized. Gadolinium-basedcontrastagentsshouldbeavoi- helpwithdiagnosingcholesteroloratheromatousemboli.
dedduetotheriskofdevelopingnephrogenicsystemicfbrosis.
Antimicrobialagentssuchasaminoglycosides,amphotericinand Diagnostic work-up
acyclovir should beavoided when possible, with doses calcu- Evaluation of urinevolume, urinary sediment and serum and
latedaccordingtorenalfunction. urinebasicmetabolicpanelisimportantforthediagnosisofAKI.
Careneedstobetakentorecognizeandmanagetreatmentof Urinalysisisoneof thekeyteststoevaluatekidneydisease
AKI complications.Whenfuidoverloadoccursinpatientswith although this is less helpful in the ICU setting as most urine
AKI, fuid intake should be restricted with a trial of diuretics specimensarecollectedfromaurinary catheter. Ultrasound is
beforedialysisinitiation.Inexperimentalstudiesontheisolated commonly used to ruleout obstructiverenal disease. Contrast
perfused kidney, furosemide has been shown to reduce renal CTs areoften needed to identify retroperitoneal fbrosis, renal
medullary injury during hypoxic conditions. Furosemide may veinthrombosis,renalinfarctionornephrocalcinosisascauseof
improvetheoxygensupplyanddemandbalancebyinhibitingNa- acute kidney injury. It is important to remember the risks of
K-Cl2 co-transporter activity and increasing prostaglandin pro- contrast-inducednephropathyinpatientswithrenalimpairment
duction andbloodfow. Morphineandnitratescan beusedto aswell astherisk of nephrogenicsystemicfbrosisin patients
alleviaterespiratorysymptoms. When fuidoverloadcannotbe exposedtogadolinium.
correctedinatimelymannerwithmedicalmanagement,positive- Arenalbiopsyshouldbeconsideredforpatientsinwhompre-
pressure ventilation may need to be initiated with or without renal andpost-renal AKI havebeenexcludedandif acauseof
endotrachealintubationanddialysis. intrinsicrenal diseaseissuspectedyetremainsunclear. Exam-
HyperkalaemiaisafrequentcomplicationofAKI andcanbe ples where it would be useful include rapidly proliferative
managed by administering parenteral glucose and insulin in- glomerulonephritis (RPGN), vasculitis, systemic lupus erythe-
fusionsandsodiumbicarbonateto promoteshift of potassium matosus,andacuteinterstitialnephritis.Askidneybiopsiespose
intotheintracellular space. Dialysisinterventionsfor thetreat- a signifcant risk it is crucial to consider if the pathological
mentofAKIshouldbeconsideredinthebroaderclinicalcontext, diagnosiswouldultimatelychangemanagement.
withtrendsoflaboratorytestsratherthanonesinglereadingand
withdueconsiderationofwhethertheconditioncanbemanaged AKIbiomarkersandearlydetectionofAKI
byinitiationofrenalreplacementtherapy(RRT). Increasingly, research efforts havebeen focussed on theearly
Nutritional supportisanimportantbutfrequentlyneglected detection of AKI as it has been known to improveoutcomes.
aspect in themanagement of AKI. Patients with AKI havean Novel serum and urine biomarkers, such as kidney injury
increased risk of protein-energy malnutrition because of poor molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin
nutritional intake and high catabolic rate. Patients with AKI (NGAL), cystatin C, interleukin (IL-18), urinary cystatin C and
shouldreceiveabasicintakeof0.8e1.0gofprotein/kg/dayand otherssuggestpotential atprognostication andidentifyingspe-
atotalenergyintakeof20e30kcal/kg/day.InpatientsonRRT, cifccausesofAKI.
1.0e1.5 g of protein per kg/day should be given up to a
maximumof1.7g/kg/dayinhypercatabolicpatients. Chronic kidneydisease
Diagnostic approachtoAKI Chronickidneydisease(CKD)isdefnedasabnormalitiesofkidney
Priorcreatinineconcentrationandevidenceofunderlyingkidney structureorfunction,presentfor>3months,withimplicationsfor
should beevaluated fromthemedical history and hospital re- health.ThecriteriafordiagnosisofCKDincludealbuminuria,urine
cords. Particular attention should be given to the medication sedimentabnormalities,electrolyteandotherabnormalitiesdueto
history especially any over-the-counter medications. Painless tubulardisorders,abnormalitiesdetectedbyhistology,structural
haematuriamay suggest glomerulonephritis or agenitourinary abnormalities detected by imaging, history of kidney trans-
malignancy, whilepainful haematuria is moreconsistent with plantation, or an estimated eGFR below 60 ml/min/1.73m2
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 400 Ó2021PublishedbyElsevierLtd.
NEPHROLOGY
persistingfor 3monthsor moreirrespectiveof thecause. CKD adequaterenal replacement for 48hoursor more. Thisensur-
shouldbeclassifedbasedonGFRcategory(G1toG5,withG3split es that the treatment is intermittent and the patient can be
into3aand3b)andalbuminuriacategory(A1,A2andA3basedon disconnectedformthecircuitforprolongedperiodsoftime.Itis
urinaryalbumin/creatinineratioinanearlymorningspoturine possible to run slower fows of dialysate through the device
sample).ClarifcationsshouldbemadetoincludethesuffxTfor (100ml/minfow),butthisreducestheeffciencyofthesolute
patientswithrenalallograftsandDtoidentifyCKDstage5patients clearance and necessitates more prolonged sessions; this low
ondialysis. effciencysetupiscalledSLED(sustainedloweffciencydialysis).
SLEDisahybridformof renal replacementtherapythatcom-
Renalreplacementtherapy binesthedesirablepropertiesofbothintermittenthaemodialysis
and continuous renal replacement therapy (CRRT). Haemody-
Inthefaceof untreatedacuterenal failure, thepatientwill die namically, itisbetter toleratedthanintermittenthaemodialysis
from accumulation of unexcreted solutes (urea, potassium,
as the rate of solute and fuid removal is slower and the
hydrogenions)orfuidoverload.Itisonlyinthelastcenturythat
metabolic control is equivalent to CRRT. It provides renal
wehavebeenabletofullyunderstandandtreatthis. The20th
replacementtherapyforextendedperiodsoftime(6e12hours)
century has seen therapid riseand subsequent refnement of
butisintermittent(threetimesaweek).Thisallowsforgreater
severalmodalitiesofrenalreplacementtherapy.Inthe1940s,Dr
mobilization and rehabilitation of the patients because of
Willem Kolff developed the frst drum dialysis machines for
scheduledtimeoffdialysis.
haemodialysis.Inthesamedecade,DrJacobFinedevelopedthe
Figure 1 gives a schematic of the process of dialysis. The
processofperitoneal dialysis.Inthe1960s,DrBerlandScribner
fgure is simplifed, instead of a single tube constructed of a
developedcontinuousarteriovenoushaemofltrationandDrBe- semipermeablemembrane,moderndialysersconsistofhundreds
rnardCanauddevelopedcontinuousvenovenoushaemofltration ofsmallhollowfbresencasedinalargercylinder.Thishasthe
in the1980s. Sincethesediscoveries, theprocesseshavebeen beneftofvastlyincreasingthesurfaceareaofmembrane(usu-
furtherrefnedtoimprovesafety,effciencyandreliability.Asa ally0.8e2.5m2)thatbloodisincontactwith,therebyincreasing
resultoftheseadvances,wenowhavearangeofoptionsforthe
therateofdiffusionandthereforesoluteclearance.Historically,
provisionofrenalreplacementinacuterenalfailure.
the membrane was composed of cellulose, although this has
largely been replaced with synthetic materials such as poly-
Intermittenthaemodialysis sulfoneandpolyacrylonitrile.
Oncetheprimemodalityofrenal replacementintheacuteand
chronicsetting,thishasbecomefarlesspopularincriticalcarein Peritonealdialysis
favourofcontinuousmodesofrenalreplacement.Itremainsfar Theperitoneumisavascularstructurecoveredwiththinmeso-
morepopularoutsideofcriticalillnessduetothecapacitytobe thelium.Thestructurecoversthegutandotherintra-abdominal
runintermittentlyratherthancontinuouslytherebyliberatingthe organsandthesurfaceoftheabdominalcavity.Ithasasurface
patientfromthemachineforlongperiodsoftime. area of 1e2 m2 which is enhanced by themicrovillaeon the
Theprincipleofhaemodialysisisthepassingofbloodovera surfaceofthemesothelium.Duetotheseproperties,itisanideal
semipermeable membrane. A dialysate is then passed on the membranefor thetransfer of water andlow molecular weight
other side of the semipermeable membrane. The dialysate is molecules.
passedintheoppositedirectiontothebloodfow (countercur- DrHenryTenchkoffdevelopedtheso-calledTenchkoffcath-
rent fow) to maximize the concentration gradient across the eterinthe1960s.Itremainslargelyunchangedtoday;asynthetic
membraneandenhancetheeffciencyofthesystem.Adialysate tubewitheitherafangeorDacroncuff(usually2Dacroncuffs)
is a solution of specially treated mains-supply water with an to ensure fxed placement is inserted through the anterior
addedconcentrateof sodium, calcium, potassium, magnesium, abdominal wall intotheperitoneal cavity. Thiscanbeinserted
chloride,acetate,citrate,bicarbonateandglucose.Mainssupply withaSeldinger(blind)technique,laparoscopicallyorviaopen
waterisrequiredduetohighvolumesofliquidinvolvedinthe surgicalapproach.
process (500e800 ml/min of dialysate fow countercurrent Adialysateisinstilledintotheperitoneal cavity.Itisusually
againstabloodfow of 250e400ml/min). Water andlow mo- comprised of sodium, calcium, magnesium, chloride, lactate,
lecularweightsubstances(roughly10kDaorlessbutdependent bicarbonateandglucose. Usual volumeis1.5e3L.Thefuidis
on thedevice) diffuseacross themembrane. This process re- usually instilled, permitted to dwell in the peritoneum while
quiresthepresenceofanosmoticgradientbetweenthetwosides soluteexchangeoccursandthenitisexpelled.Thisusuallyoc-
of the membrane (blood and dialysate). Brownian (random) cursviaautomateddevicewhilethepatientisasleepovernight.
particlemovementwillfavourabulkmovementofsolute(small Adoseofdialysatecanbelefttodwellinthepatientduringthe
particlessuchasurea) tothesideofhighconcentrationtolow day for ongoingcontinuous ambulatory dialysisor thepatient
concentrationandwateralongsideit.Therefore,waterwillpass canbeleft’dry’duringthedaywithnoindwellingfuid.
acrossthemembraneonlyifthedialysateissuitablyhypertonic Theperitoneumis asemipermeablemembrane; as such, it
compared to blood, and electrolytes (such as sodiumand po- actsakintothemembraneinadialysismachineandallowssmall
tassium) will only beremoved fromtheblood if thedialysate molecules such as urea to diffusefromtheblood to thefuid
containslowerconcentrationsoftheelectrolytesthantheblood. acrossalongtheconcentration gradient. Theosmolality of the
Thisprocessofsoluteremovalifreferredtoasdiffusion. dialysate(largely dueto high glucosecontent) also createsan
Soluteclearanceisgreater than normal renal clearanceand osmoticpressurethatdragswaterandsolutesintothefuidvia
itispossibleforasessionofdialysislasting2e4hourstoprovide ultrafltration.
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 401 Ó2021PublishedbyElsevierLtd.
NEPHROLOGY
Haemodialysis
Bubble detector
+ clamp
Fresh dialysate in
Pump Used dialysate out
Anticoagulant
infusion
Figure1
Severalfactorsmakethismethodofdialysislessfavourablein larger cylinder. Thedifferenceliesinthemechanismbywhich
criticallyill patients, includingthereducedcontrol offuidbal- thesolutesandwaterpassacrossthemembrane.Unlikedialysis,
ance,variablesoluteclearance,peritonealinfectionrisk,protein ahydrostaticpressureismaintainedwithinthefbresoftheflter.
lossandincreaseinabdominalpressures.Peritonealdialysishas This pressureacross themembrane(so called transmembrane
beendemonstratedtoconferahighermortalityriskascompared pressuree TMP)drivessolutesandwateracrossthemembrane
tocontinuoushaemofltrationincriticalcare. without therequirement of an osmoticgradient to promoteit.
The mechanism of driving the solutes across the membrane
Continuous haemofiltration usingpressureisreferredtoasconvection.
Thismethodofrenal replacementtherapyisthemostrecentto The rate of ultrafltrate production (Qf) depends upon the
bedevelopedascomparedtoother modalities, butithasrisen membranepermeabilitycoeffcient(Km)andtheTMP:
intopositionasthemostpreferredmethodofrenalreplacement
therapy in critical care, especially in high resource countries. Qf ¼Km TMP
Thereareseveralreasonsforthisincluding:
improvedhaemodynamicstability Figure2givesaschematicoftheequipmentarrangementfor
greatercontrolofpHandelectrolyteimbalances CVVHF.Bloodfowisusuallystaticatapproximately200ml/min.
greater capacity to extract fuid from the vascular ApumpcontrollingtheultrafltrateremovalmanipulatestheTMP
compartmentinfuidoverloadedpatients bycontrollingthepressureonthatsideofthecircuit.Thisensures
less rise in intracranial pressure as compared to other that theultrafltratefow can bemaintained at aconstant rate
methods evenasthemembranepermeabilityalters(ittendstoreduceover
lowinfectionrisk time). Another key differencebetween haemodialysis and hae-
norequirementforspecifctreatedwatersupply mofltration is theremoval of water and electrolytes from the
simpletouseandtrainstafftooperate patient. Thisistargetedby thecomposition of thedialysatein
Originally,thecontinuoushaemofltrationwasdesignedtobe dialysis;inhaemofltration,waterandallsubstancessmallerthan
connected to thepatient viaadesignated arterial cannulaand theporesizeofthesemipermeablemembranearefltered.This
venous cannula. Blood fowed through the circuit from the resultsinlargevolumesoffuidandelectrolytelosswhichmuch
arterial access to venous return under mean arterial pressure. bereplacedinthecircuit.Replacementfuidcanbeaddedbefore
This has subsequently been replaced by dual lumen venous the flter (predilution), after (postdilution), or a mix of both.
cathetersthatprovideaccessandreturnportsinthesamecan- Replacementfuidcontainswaterandmostelectrolytespresentin
nulaandtheadditionofpumpswithinthecircuittoensurethat plasma. It is usually buffered with lactate and bicarbonate.
thefowisindependentofpatientbloodpressureandavoidsthe Phosphateisoften absent fromreplacement fuid and it isnot
requirement for arterial vascular access. This is referred to as uncommonforpatientstorequirephosphatereplacementwhen
continuousvenovenoushaemofltration(CVVHF). receivinghaemofltration.Predilutionreducesthehaematocritof
Theprocess has similarities to dialysis, insofar as blood is theblood and potentially increases theuseablelifetimeof the
pumped out of the patient and passed over a semipermeable flterbeforeitclotsbutreducestheeffciencyoftheflter.Ultra-
membranewheresolutesandwater passthrough poresin the fltratedoseisprescribedaccordingtoweight(ml/kg/h). There
membrane. Theflter (likeadialyser) isalsoarrangedashun- has been virtually no demonstrated beneft from high volume
dredsof hollow fbresof themembranematerial encased in a haemofltration (35e40 ml/kg/h) as compared to low volume
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 402 Ó2021PublishedbyElsevierLtd.
NEPHROLOGY
Continuous venovenous haemofltration
Anticoagulant
reversal (if used)
Bubble detector
+ clamp
Replacement
fuid
Effuent out
Pump
Anticoagulant
infusion
Figure2
haemofltration(20e25ml/kg/h)inacutekidneyinjuryandlow pathways. This results in formation of blood clots within the
volumeprescriptionsareusuallyfavoured. circuit,specifcallyclottingandfailureofthedialyser/flter.Im-
ItispossibletomodifyaCVVHFcircuittopassadialysateover provementsinmaterialshavereducedthiseffectovertimeandit
thesemipermeablemembraneinacountercurrentfow(Figure3). is possible to run both dialysis and haemofltration circuits
Thisisreferredtoascontinuousvenovenoushaemodiafltration withoutanticoagulation,butitremainsrecommendedthatanti-
(CVVHDF) and it enhances soluteclearanceby permittingcon- coagulationisusedtoreducetheriskofcircuitfailure.
vectionanddiffusiontooccur. Forcontinuousrenal replacementtherapiesthereareseveral
options
Anticoagulation systemicanticoagulationwithunfractionatedheparin
Whenbloodispassedinanextracorporealcircuitandexposedto regionalanticoagulationwithunfractionatedheparin
synthetic materials it triggers activation of the coagulation regionalanticoagulationwithcitrate.
Continuous venovenous haemodiafiltration
Anticoagulant
reversal (if used)
Replacement
Bubble detector fuid
+ clamp
Fresh dialysate in
Pump Used dialysate out
Anticoagulant
infusion
Figure3
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 403 Ó2021PublishedbyElsevierLtd.
NEPHROLOGY
Chelation of calcium by sodium citrate
O O– O– O
Ca2+
Na+O– O– Na+
O O
OH
O O– +3[Ca2+] OH +6[Na+]
Na+
O–
O
+
Na+O– O Ca2+
O– O
OH
O O OH
O– O– Na+
Na+
Ca2+
O O– O– O
Figure4
Systemicanticoagulationinvolvesanticoagulatingthepatient normalizedpriortore-enteringthepatient.Thisisnowuncom-
andtheextracorporealcircuitbyaddingheparinviaabolusand monly used as patients with a bleeding risk are now usually
continuousinfusion. Theactivatedpartial thromboplastin time fltered without anticoagulation or with regional citrate anti-
(APTT)ischeckedandatargetAPTTratioof1.5e2.5isusual.In coagulationifavailable.
patientswithahighbleedingrisk,itispossibletoaddthehep- Regional citrateanticoagulation involvesaddingsodiumcit-
arin in theafferent limb of thecircuit, theeffect can then be ratetotheafferentlimbofthecircuit. Thischelatescalciumin
reversedintheefferentlimbofthecircuitwithacalculateddose thebloodandinhibitscoagulationinthecircuit(Figure4). An
ofprotamine.Thisisreferredtoasregionalanticoagulation,with infusion of calciumchlorideor gluconateisthen addedto the
anticoagulanteffectonlypresentinthebloodbetweenthehep- efferentlimbofthecircuittoovercometheeffectofthecitrate
arin and protamine infusions, the blood coagulation status is andnormalizecoagulationbeforeitre-entersthepatient.Serum
Citrate cycle
Glycolysis
Exogenous Citrate
Acetyl CoA Coenzyme A from anticoagulation
H O
2
Citrate
Oxaloacetate
H O
NADH 2
NAD+
cis-Aconitate
Malate
H O
H O 2
2
Fumarate Isocitrate
FADH NAD+
FAD NADH
CO
Succinate 2
α–Ketoglutarate
GTP NAD+
GDP+Pi Succinyl CoA NADH
CO
2
Figure5
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 404 Ó2021PublishedbyElsevierLtd.
NEPHROLOGY
ionized calciumlevels aremeasured fromthepatient and the Serumlactateismeasuredtohelpidentifythosewhoareatrisk
calciumreplacementistitratedaccordingly.Thecitrateismostly ofdevelopingcitratetoxicity.
removedviatheflter,anyremainingcalcium/citratecomplexes Prostacyclin can also be used to anticoagulated for renal
arethenmetabolizedintheliverwhereitentersthecitratecycle replacementtherapy.Itishaspotentvasodilator,anti-thrombotic
asanenergysubstrate(Figure5).Theexcesscitrateamountstoa andanti-plateletproperties.Theagenthasbeenusedasheparin
signifcant alkali load and specialized replacement fuids with sparingmoleculeduringrenalreplacementtherapy. A
reducedbicarbonateareneeded.
Regional citrateanticoagulationhasbeenshowntoincrease
the circuit life and decrease the rate of complications as Keylearningpoints
compared to systemic heparin anticoagulation. However,
implementation of regional citrate anticoagulation requires
C Acutekidneyinjuryhassignifcantmorbidityandmortality
established protocols and extensive staff training in order to
C Itcanbecausebepre-renal,renalorpost-renalcauses.IntheICU
avoidpotentialcomplications.
settingitisoftenmulti-factorial
Citrateaccumulation/toxicity: oneof thepotentiallyse-
C Optimizingfuidmanagementandpreventingnephrotoxinsiskey
verecomplications of regional citrateanticoagulation. It
inpreventionandmanagementofAKI
occurswhenbodyisunabletometabolizeallthecalcium
C Dialysisworksviadiffusion
citratecomplexes.Patientsathighriskarethosewithliver
C Filtrationworksviaconvection
failure, cardiogenic shock and elevated serum lactate.
C Peritoneal dialysisisinferiortohaemodialysisandhaemofltra-
Citrate accumulation is suggested by high anion gap
tioninacuterenalfailurebutmaybeappropriateinalow
metabolicacidosis, escalatingcalciumsubstitution needs
resourcesetting
andanelevatedtotaltoionizedcalciumratio(>2.5).
C Anticoagulationisrecommendedandsystemicheparin,regional
Citrate overload: morecommon and easily manageable
citrateorzeroanticoagulationaretheusualoptions
complications of regional citrate anticoagulation. Meta-
bolicconversionfromaccumulatedcitratecanresultinan
excessivealkaliloadandmetabolicalkalosis.
Systemicionizedcalciumrequiresmonitoring. Normal (1.15
e1.3 mmol/l) ionized calcium levels should be maintained FURTHERREADING
throughout therapy. Baseline measurement should be taken DaugirdasJT,BlakePG,IngTS.Handbookofdialysis.5thEdn.Phil-
beforestartingthetherapywhich isusedto setinitial calcium adelphia:WoltersKluwerHealth,2015.
infusionrate.Total/ionizedcalciumratioiscalculated;incaseof JohnsonRJ,FeehallyJ,FloegeJ.Comprehensiveclinicalnephrology.
citrateaccumulation,non-metabolizedcalciumcitratecomplexes 5thEdn.Philadelphia:ElsevierSaunders,2015.
continuetocirculateinthebloodeffectivelyincreasingthenon- Kidneydisease:improvingglobaloutcomes(KDIGO)acutekidney
ionized fraction of total calcium. A total/ionized calciumratio injuryworkgroupKDIGOclinicalpracticeguidelineforacutekidney
over 2.5ishighlysuggestiveof calciumaccumulation/toxicity. injury.KidneyIntSuppl2012;2:1e138.
ANAESTHESIAANDINTENSIVECAREMEDICINE22:7 405 Ó2021PublishedbyElsevierLtd.