Download TIME PASSAGES: CHRONIC KIDNEY DISEASE 1 AND 2 Joe

TIMEPASSAGES:CHRONICKIDNEYDISEASE1AND2
JoeBartges,DVM,PhD,DACVIM,DACVN
ProfessorofMedicineandNutrition
TheUniversityofGeorgia
[email protected]
GeneralKeyPoints:
• CKDimpliesirreversiblerenalfailurethatremainsstableforaperiodoftime,butultimatelyprogresses
• Incidenceincreaseswithincreasingageindogsandcats
* Althoughmanythingscancausechronickidneydisease,bythetimechronickidneydiseaseisdiagnosedthe
cause(s)is/arenotpresentandnottreatable.Itcanoccurasaresultof:
* Congenitalrenaldisease
* Acquireddiseases–hypotension,drugs,toxins,hypotension,infections,cancer
* Periodontaldiseasehasbeenlinkedtorenalhistologicchangesindogs
* Felineimmunodeficiencyvirusinfectionhasbeenlinkedtorenaldiseaseincats
* Kidneysareinvolvedwithwholebodyhomeostasis;therefore,CKDaffectsgeneralwell-being
* Clinicalsignsinvolveprimarily
* Changeinwaterbalance:polyuria/polydipsia(PU/PD)
* Gastrointestinalsigns(vomiting,hyporexia/anorexia,halitosis)
* Signsofchronicdisease(weightloss,lossofbodycondition,unkemptappearance)
* Laboratoryevaluationreveals
* Azotemia
* Inappropriatelydiluteurine
* Hyperphosphatemia
* Metabolicacidosis
* ±Hypokalemia
* ±Non-regenerativeanemia
* ±BacterialUTI
* Kidneysareoftensmallandirregularonpalpation,abdominalradiographyandabdominal
ultrasonography;however,somecausesofchronickidneydiseaseareassociatedwithrenomegaly(ie
neoplasia)
* ±Systemicarterialhypertensionoccursin65-80%ofpatients
* ±Proteinuria(microalbuminuria,macroalbuminuria)
* ProgressionofCKD
* Thecause(s)ofprogressionofCKDisnotcompletelyknown
* Itislikelythatintypicalsituation,CKDresultsfromrepeatedinsultsovertimethatresultin
sequentiallossofnephrons
* ThecompensatoryresponseisanincreaseinsinglenephronGFRinthesurvivingnephrons
* ThisresultsinmaintenanceoftotalGFRdespitelossoffunctionalrenaltissue(renalreserve)
* Thereisdilationoftheafferentarteriole
* Increaseinintraglomerularpressure
* TheresultisincreaseinGFRandrenalbloodflow
* Therearetrade-offs,however:
* IncreaseinGFRduetoincreaseinrenalbloodflowandintraglomerularpressureincreases
likelihoodofincreasedproteinloss
* Increasedintraglomerularpressureistransmitteddistally
* Thereisactivationandreleaseofgrowthfactorsthatpromotetubulointerstitialfibrosisand
glomerulosclerosis
* Eventually,theseadaptationsresultinlossoffurthernephronsandthecyclecontinues
* Overtime,renalreserveislostasthethresholdofnephronmasslossissurpassedresultingin
progressionofCKDtoendstage
InternationalRenalInsufficiencySociety(IRIS)Staging
* TheInternationalRenalInsufficiencySociety(http://www.IRIS-kidney.com)hasdevelopedstagingsystem
foranimalswithCKDandtreatmentbasedonstaging.
• ThestagingsystemisdesignedforusewithdogsandcatswithCKD.AdiagnosisofCKDismadefirstand
stagingisaccomplishedbyevaluating
o (1)2serumcreatininevalueswhenpatientiswellhydrated,
o (2)2to3urineUPCand
o (3)2to3indirectarterialbloodpressuredeterminations.
§ Indirectarterialbloodpressureisdeterminedby1of2methods
• Doppler:thisutilizesultrasonographicwavesthataretransmittedbya
piezoelectriccrystalandisreflectedbacktothecrystalandthenconvertedto
audiblesound
o ItutilizestheDopplershifteffect–youknowthesoundanambulance
orracecarmakesasitapproachesandthendrivesbyyou(?)
o Bloodinanarteryismovingwhilesurroundingtissueisnot
o Itisverygoodforsystolicbloodpressure,butisnotveryaccuratefor
measuringdiastolicandmeanarterialpressure
o Acuffisplacedoverthearteryproximaltoplacementofthe
piezoelectriccrystal
o Thecrystalisplacedonashavedareaovertheartery
o Thecuffisinflatedabovesystolicbloodpressuresonoflowofblood
occursintheartery
o Thecuffisslowlyreleaseduntilbloodflowisre-established,whichis
thesystolicbloodpressure
o Asphygmomanometer(gauge)isusedtogiveanumericvaluetothe
systolicpressure
• Oscillometric:thisutilizestheprincipleofmovement(oscillations)andthe
intensityofvascularwallvibration(movement)fromthepressure
o Itcandeterminesystolic,diastolic,andmeanarterialpressure
o Althoughuseful,itislessaccuratethenDoppler
o Acuffattachedtotheoscillometricbloodpressureinstrumentis
placedoveranartery.Noclippingisnecessary
o Pressureinthecuffisincreaseduntilitexceedssystolicbloodpressure
andnoflowofbloodoccursintheartery
o Theinstrumentslowlyreleasespressurefromthecuffanddetects
vascularwallvibrationsasbloodflowisre-established.
§ Thefirstvibration=systolic
§ Themostintensevibration=mean
§ Thepointwherevibrationsleveloff=diastolic
• Indirectarterialbloodpressureisdeterminedoverthepalmarmetacarpal,
cranialtibial,orcoccygealarteries
• Itisimportanttoperformwhenpatientisnotstressed;therefore,havingthe
ownerhold,useminimalrestraint,performawayfrompeopleandother
patients,andperformpriortosamplecollectionandphysicalexamination
• Systemicarterialhypertensionmayoccurin65-75%ofdogsandcatswithCKD
o CKDisstagedbymagnitudeofrenaldysfunctionandfurthermodified(sub-staged)bypresence
orabsenceofproteinuriaand/orhypertension.ProteinuriaONLYreferstorenalproteinuriaand
notpre-renal(e.g.hyperglobulinemia)orpost-renal(e.g.urinarytractinfection,hematuria,etc),
andisbasedonUPC.Bloodpressuredeterminationshouldbeperformedseveraltimesinorder
toaccountfora“whitecoat”effectusingastandardprotocol.
Stage
Plasmacreatinine
mg/dl
Dogs
Cats
1
<1.4
2
1.4-2.0
3
4
2.1-5.0
>5.0
Comments
Non-azotemicSomeotherrenalabnormalitypresente.g.inadequate
concentratingabilitywithoutidentifiablenon-renalcause;abnormalrenal
<1.6
palpationand/orabnormalrenalimagingfindings;proteinuriaofrenalorigin;
abnormalrenalbiopsyresults
Mildrenalazotemia[lowerendoftherangelieswithinthereferencerangefor
manylabsbuttheinsensitivityofcreatinineasascreeningtestmeansthat
1.6-2.8
animalswithcreatininevaluesclosetotheupperlimitofnormalityoftenhave
excretoryfailure]Clinicalsignsusuallymildorabsent
2.9–5.0 ModeraterenalazotaemiaManysystemicclinicalsignsmaybepresent
>5.0
SevererenalazotaemiaManyextra-renalclinicalsignspresent
UPCvalue
Dogs
<0.2
0.2to0.5
>0.5
Cats
<0.2
0.2to0.4
>0.4
Substage
Non-proteinuric(NP)
Borderlineproteinuric(BP)
Proteinuric(P)
SystolicBPmmHg
DiastolicBPmmHg
<150
150–159
160–179
=180
<95
95-99
100-119
=120
Adaptationwhenbreed-specific
referencerangeisavailable*
<10mmHgabovereferencerange
10–20mmHgabovereferencerange
20–40mmHgabovereferencerange
=40mmHgabovereferencerange
Substage
AP0:MinimalRisk(N)
AP1:LowRisk(L)
AP2:ModerateRisk(M)
AP3:HighRisk(H)
Noevidenceofendorgandamage/complications
Nocomplications(nc)
Evidenceofendorgandamage/complications
Complications(c)
Bloodpressurenotmeasured
Risknotdetermined(RND)
TestsofRenalFunction
• GFRcanbeestimatedusingbothclearancemethodsand“spot”orsingletimepointtests.
o Renalorplasmaclearanceofaninjectedsubstance(e.g.,iohexol,creatinine)ismostaccurate
estimateofGFR
o MoresensitivemeansfordetectingearlyCKDthanspotmethodsofGFRestimation.
o Determiningplasmaclearancecanbearelativelyexpensiveandtime-consumingprocedure.
o Mostoftenperformed:
§ ToestablishadecreaseinGFRwhenclinicalparameters(e.g.,poorlyconcentratedurine)
createsuspicionforCKDbutcannotconfirmitspresence,
§ Todeterminedosageregimensfortherapeuticagentswhoseexcretionisprimarilyrenalin
patientswithCKD.
• Plasmaclearancetesting
o Measuringreductionofaninjectedsubstanceinthebloodovertime)canbeusedtoestimaterenal
clearanceandthereforeGFR.
§ MostcommonexogenoussubstancesusedinveterinarymedicineforestimationofGFRare
iohexolandcreatinine.
§ Othersubstancesandtechniquescanbeused,suchasinulin,radiolabeledmarkers,and
contrast-enhancedcomputedtomography(CT)
§ Anovelfluorescenttracerhasbeenevaluatedasarapid,non-invasivebedsidetestindogs.
Ultimately,choiceinmethoduseddependsonavailabilityofteinjectedsubstanceand
methodofmeasurementaswellastheexperience
§ Insomecases,estimationofindividualkidneyGFR(vs.globalGFR)isnecessary,asispossible
withscintigraphyorCT.
o IohexolclearanceandexogenouscreatinineclearancegiveameasureoftotalGFR;DTPA(a
radiolabelledmarker)givesestimateoftotalaswellasindividualkidneyGFR.
o Oneofthemainlimitationswithclearancemethodsisneedforserial,preciselytimedblooddraws.
§ Anaccurateclearancecalculationrequiresasmanyas8post-injectionbloodsamplesover6
hoursorlonger,althoughreasonableestimatescanbeobtainedwithlimitedsampling(i.e.,2
or3post-injectionsamples)
§ Timingoftheselimitedsamplecollectionsvariesdependingonthesubstanceused
§ Somestudieshavefoundthatcalculationofplasmaclearancebasedonasinglepostinjectionsampleisstronglycorrelatedwith3-sampletechniques,aslongasanestimated
volumeofdistributioncanbedetermined
§ Thisisespeciallyimportantincats,wheremultiplecollectionscanprovedifficult.
o Anotherlimitationwithplasmaclearanceisthelargeamountofvariabilityinwhatisconsideredtobe
“normal”indogsandcats.
§ Inonestudyof118healthydogs,iohexolclearancerangedfrom0.95-4.25mL/min/kg
§ Inpreviouslypublishedstudiesinhealthydogsandcats,therangeforvariousclearance
estimateswasaswideas2.45-6.64mL/min/kg(dogs)and2.19-3.49mL/min/kg(cats),
althoughmostweightedreferenceintervalswerearound3-4mL/min/kg(dogs)and2.5-3.5
mL/min/kg(cats)
§ Therefore,itisdifficulttodefineanormalGFRinaparticularanimalwithoutabaselinefor
thatpatient,anditlimitsabilityofplasmaclearancetodetectearlyreductionsinGFR.
o Week-to-weekandmonth-to-monthbiologicalvariabilitymustalsobeconsideredwhenmonitoring
plasmaclearanceinaparticularpatient
§ Basedontheweek-to-weekvariabilityofiohexolclearanceinacohortofdogswithmildbut
stablerenaldisease,asubsequentmeasurementmustincreaseordecreasebyupto20%in
ordertobe95%confidentthatatruechangeinclearancehasoccurred
§ Interestingly,despiteusingmoremeasurements,eachwithitsowninherentvariability,
iohexolclearancevariabilitywassimilartothatforserumcreatinine(sCr)inthesedogs
o Inadditiontobiologicalconsiderations,analyticalconsiderationsinplasmaclearancecalculationsare
important.
§ Whenusingalimitedsamplingtechnique,acorrectionformulamustbeappliedtocorrect
fortheinitialdistributionphaseinordertoavoidoverestimationoftheGFR
§ Correctionformulasforbothdogsandcatsareavailablewhenusingiohexol
§ Normalizationtobodyweight,surfacearea,orextracellularvolumehasbeenrecommended,
butitisnotclearwhichnormalizationtechniqueshouldbeusedindogsandcats.
Spottests
o Urinespecificgravity(USG)
§ USGvariesfromminute-to-minuteandisinfluencedbyhydrationandvolumestatus
§ AdiluteUSGonaspotsamplemaybenormalinpatientsthathaveingestedwaterrecently
inexcessofwhatisrequiredforhydration
§ Additionally,manynon-renaldisordersinfluenceUSGbyalteringvolumestatusand/orby
inhibitinganti-diuretichormonefunctioninthedistalrenaltubuleandcollectingduct
§ PatientswithpersistentPU/PDmaynothaverenaldiseaseandotherdisordersshouldbe
ruledoutifnotazotemic(e.g.hyperadrenocorticism,hypothyroidism,hyperthyroidism,
diabetesmellitus,hypercalcemia,hepaticdisease,consumptionofhighersodiumchloride
diets,administrationofdiuretics,supplements,orherbswithdiureticactivity,etc).
o Bloodureanitrogen(BUN
§ Usedasbiomarkerforassessmentofrenalfunction
§ Moreinfluencedbynon-renalfactorsthanserumcreatinine–e.g.pre-renalandpost-renal
§
•
Ureanitrogenisasmallmoleculethatdiffuseseasilyacrosscellmembranesandintoandout
oftissues
• Withdehydration,ureanitrogenisreabsorbedintubulesandlessisfiltereddueto
decreasedrenalbloodflow;therefore,itincreasesmorequicklyandoftentoa
greaterdegreethancreatinine
• Ureaisproducedfrommetabolismofammoniabyhepaticureacycle;therefore,
increasedintestinalproteinloadwillresultingenerationofmoreammoniaand
ureanitrogen
• Itshouldnotbeusedasasolebiomarkerforrenalfunctionandinterpretationofan
elevationisnotpossiblewithouthistoricalandphysicalexaminationfindingsanda
urinespecificgravity
Serumcreatinine(sCr)
§ MainendogenousmarkercurrentlyusedforestimatingGFR
• WhilethismoleculemeetsmostofthecriteriaforanidealmarkerofGFR,ithas
severalmajorlimitations,ofwhichthemostimportantinveterinarymedicine
includebreedvariationsindogsanddecreasedproductionwithmusclewasting,as
isoftenthecaseinanimalswithCKD.
• Itmayoverestimaterenalfunctionincachectic,geriatric,andveryyoungpatients.
• TubularsecretioncanincreaseassCrincreases,althoughthisisthoughttobe
minimalinveterinaryspeciesascomparedwithhumans.
• ThesefactorscanmakemonitoringofsCrovertimealessreliableindicatorof
decliningGFR.
§ Earlyindisease,limitationsofsCrinanindividualpatientareminimal.
• Musclemassisusuallystableindogsandcatswithearlyrenaldisease,andtubular
secretionduetoanincreasedbloodconcentrationisnotafactor.
• Carefulmonitoringandtrendingoffastedserumcreatinineconcentrationscan
allowforearlydetectionofrenaldiseasemanifestedbyadecliningGFR.
• TrendingsCrmeansthatserialdeterminationsofsCrareassessedtolookfor
significantincreasesinaparticularpatientthatarelikelytoreflectworseningrenal
function.
• Serumcreatinineconcentrationlendsitselftotrendingquitenicelybecauseit
demonstratesverylittleintra-individualvariationinhealthy,adultanimals,even
overseveralyears
• SmallincreaseswithinthereferenceintervalcanreflectsignificantdecreasesinGFR
inanindividualpatient,andareferenceintervalwillnotbehelpfulwhenusingsCr
toidentifytheearliestdeclinesinGFRduetokidneydiseaseinmostpatients.
• WhencomparingserialmeasurementsofsCrwithrenalclearanceofanexogenous
substance,theycorrelatestronglyandsubtleincreasesinsCrcanidentifya
decreaseinGFRatasimilarpointindiseaseprogression(unpublished
observations).
• WhiletrendingofsCrcanbeusefulintheearlydetectionofrenaldisease,many
patientspresenttoaclinicwithnopriorbloodwork.
o Inthiscase,thevariousfactorsthatcaninfluencesCrneedtobe
considered(e.g.,breed,age,musclemass,diet/fastingstatus,hydration
status)whenevaluatingasinglevalue.
o Anyconcerningvalues,evenwithinthereferenceinterval,shouldprompt
furtherevaluation.
WhentrendingsCr,beawareofbothitsbiologicalandanalyticalvariability.
§ Biologicalvariabilityinanindividualpatientisbestdeterminedbybloodworkperformed
duringroutinehealthchecks.
§ Aslongasatleast3measurementshavebeenobtained,onecancalculatethereference
changevalue(RCV)forapatient
§
o
o
Thisvaluerepresentsthatatwhichonecanbe95%confidentthatanincreaseor
decreaseintheanalytehasoccurred.
• Somereferencelaboratoriesareincorporatingsimilarstatisticalanalysesintotheir
reportstoalloweasytrendingofvariousbloodanalytes.
• Ifenoughpreviousbloodworkresultsarenotavailableforaparticularpatient,
anotherguidethatcanbeusedistheRCVdeterminedinapopulationofdogswith
mild(sCr<2mg/dl)butstablerenaldisease.
• Total(biological+analytical)variabilityofsCrdeterminedovera3-weekperiodin
thesedogs,andtheRCVwas0.2mg/dl,meaningthatanincreaseinsCrof0.2
mg/dlwouldindicateastatisticallysignificantincreaseinthismarkerwhensCr<2
mg/dl
o Inadditiontobiologicalvariability,analyticalvariabilityisafactorintheassessmentofsCr
§ MostreferencelaboratoryinstrumentshaveexcellentprecisionintheirsCrmeasurement,
havingacoefficientofvariation<5%.
§ ThedifferencebetweensCrmeasurementsinthesamesamplecanbeasmuchas0.2mg/dl
inmildlyazotemicsamplesusingthesameinstrumentandmuchhigherinmoderatelyto
markedlyazotemicsamplesorifdifferentinstrumentsareused
§ Manyin-clinicinstrumentshaveminimal,ifany,qualityassuranceprogramsinplaceto
ensureoptimalperformance.
§ Basedonboththebiasandimprecisionfoundininstrumentscommonlyusedinveterinary
laboratories,theASCVPQualityAssuranceandLaboratoryStandardsCommitteehasset
theirtotalallowableerror(TEa)guidelineforsCrat20%
• Thismeansthatanalyticallyvariabilityalonecouldpotentiallyaccountforan
increaseordecreaseinsCrof≥0.2mg/dl.
• ItisparticularlyimportantthatserialdeterminationsofsCraremeasuredonthe
sameinstrument,ideallyonethatissubjectedtoastrictqualityassuranceprogram.
CystatinC
o CystatinCisacysteineproteaseinhibitorthatisproducedataconstantlevelinallnucleatedcells.
§ ItsharesmanyofthesamepropertiesofanidealmarkerofGFRassCr.
§ Non-renalinfluencesappearminimal,althoughadministrationoflargedosesof
glucocorticoids,thyroiddysfunction,andsomemalignanciescanincreaseitsproduction
§ Indogs,cystatinCmightbeinfluencedbyage,weight,anddietaryintake,althoughseveral
conflictingstudiesexist
§ ThebiologicalvariationofcystatinC(inter-andintra-individualvariation)issimilarto
creatinineinhealthydog
§ Itsavailabilityinveterinarymedicineisstilllimited,andtherehasbeennoverificationthat
thecystatinbeingmeasuredistrulycaninecystatinC(vs.othercystatins).
o Inhumans,themajorityofstudiessupportthatcystatinCisamoresensitiveandaccuratemarker
thansCrfordetectingearlydeclinesinGFR,particularlyinthosesubpopulationsinwhichthe
limitationsofsCrareovertlyrecognized
§ Indogs,studieshaveshowncystatinCtobeeithercomparabletoormoresensitivethansCr
todeclinesinGFR
§ ItmightthereforebeareasonablealternativetosCrindetectingdecreasedGFRduetorenal
disease.
§ ItsvalueoversCrandtheinfluenceofnonrenalfactorsonitslevelarestillunknownin
veterinarymedicine.
o Incats,measurementofcystatinChasrecentlybeendeterminedusingbothahuman-basedassay
andafeline-specificassay
§ BothofthesestudiesdemonstratedhighserumandurinecystatinCconcentrationsincats
withCKDcomparedwithhealthycats.
Symmetricdimethylarginine(SDMA)
o SDMAisasmallmoleculethatoriginatesfromhydrolysisofmethylatedproteins.
•
•
•
ThismoleculehasshowngreatpromiseasanendogenousmarkerofGFRasitappearstobe
exclusivelyeliminatedbyglomerularfiltration,andsignificantextra-renalinfluencesonits
productionandeliminationhavenotyetbeenidentified
o
§ Itisstableinwholeblood,serum,andplasmaat4 Candroomtemperatureforupto7days,
anditisnotalteredwithfreezinginserumorplasma
§ Thismoleculehasbeenevaluatedinseveralcaninestudies.
• IndogswithrapidlyprogressingCKD,SDMAcorrelatedstronglywithGFRestimated
usingiohexolclearance
• Notably,whenusingreferenceintervals,SDMAidentifiedadecreaseinGFRearlier
thansCr,however,whenbothweretrendedovertime,nomajordifferencesin
identificationofdecliningGFRwerenoted
o SDMAchangedapproximately9monthsearlierthansCr
• TheseresultssupportthattrendingofsCrisnecessaryforsensitivedetectionof
decreasingGFRandthatSDMAmightbeausefuladjuncttosCrinidentificationof
renaldisease,particularlygiventhetendencytoclassifyadogasazotemicornot
basedonareferenceinterval.
• SDMAisnotinfluencedbymusclemass,butanynon-renalchangeinGFRwill
impactit.Forexample,withdehydrationthereisadecreaseinGFRandtherefore
SDMAwillalsobeinfluenced.
• ItmightproveespeciallyusefulintheinitialdiagnosisofCKDinthosepatientsfor
whichsCrwillnotprovideareliableestimateofGFR.
IncatswithCKD,SDMAcorrelateswithsCr
§ WhilepreliminarydatasuggestthatSDMAmightincreasebeyonditsreferenceinterval
beforesCrincatsandthatahigherSDMA:creatinineratiomightindicateaworseprognosis
• Similartodogs,itisnotinfluencedbyleanbodymass;however,non-renalfactors
affectingGFRwillimpactSDMA
• SDMAchangedapproximately17monthsearlierthansCr
§
o
MANAGEMENTOFCKD
* GoalofmanagementistominimizeexcessesanddeficitsinducedbyCKDinordertoimprovequalityand
quantityofpatient’slife
* SummarizedusingtheacronymNEPHRONS
N
Nephrons
E
Electrolytes
P
pHofblood(acid-basestatus),proteinuria
H
Hydrationstatus
R
Retentionofwastes
O
Otherrenalinsults–avoid
N
Neuroendocrinechanges
S
Serialmonitoring
* NUTRITION
* Maintainadequatetooptimumbodyconditionandadequatemusclecondition(leanbodymass)
* Bodyconditionscoring(youwilllearninnutrition)
* Wantabodyconditionscoreof3/5or5/9
* Thereareformulaetoestimatedailycaloricrequirements(youwilllearninnutrition)
* Anorexiaandnauseaoccurcommonlywithchronickidneydisease.Treatmentincludes:
* Minimizingexcessesanddeficiencies
* Feedingahighlypalatabledietorincreasingpalatabilityofdiet–addwatertodogfood,use
flavoringagents,warmfoodtonearbodytemperature
* Modifyingfeedingpatterns–feedfrequentsmallmeals,offerrewards,preventfoodaversion
* Treaturemicgastroenteritis
*
*
*
*
*
*
DietaryproteininducesgastricHClsecretion;therefore,dietaryproteinrestrictionis
associatedwithdecreasinggastricacid
* GastrinlevelsareincreasedwithCKD
* GastrinstimulatesHClproductionandsecretionbygastricparietalcells
* Resultsingastrichyperacidity
* H2blockers:decreaseHClsecretionbyblockingthehistamine-2receptoronparietalcellsof
stomach.ItisreasonabletoputallpatientswithCKDonthese(e.g.Ranitidine,Famotidine)
* ProtonpumpinhibitorsinterferewithproductionofHClbythegastricparietalcellsandare
morepotentantacidsthanH2blockers.Thereisasmallstudythatdidnotdemonstratea
benefitindogswithCKD.
* Sucralfate:amucosalprotectantthatformsa“physiologicband-aid”onactiveulcersby
bindingtoexposedsubmucosalcollageninanacidicenvironment.Mayalsohave
cytoprotectanteffectsviaPGE2.Additionally,itisaweakantacidandphosphatebinderasit
containsaluminumhydroxide.
* Antacid:arenottypicallyusedwithCKDalthoughmanyareavailable.Usuallytheseare
usedasphosphatebinders.
* Mirtazapine(Remeron):anoradrenergicandserotonergicantidepressant.Itstimulates
appetiteandisananti-emetic.IthasbeenshowneffectiveincatswithCKD
* Maropitant(Cerenia):aneurokinin-1(NK-1)antagonistthatisusedformotionsicknessand
isananti-emetic.IthasbeenshowneffectiveindogswithCKD
* Misoprostol(Cytotec):aprostaglandinE2analogthatincreasesbloodflowtogastricmucosa
andincreasesstirlayeronmucosalsurface.Notusedroutinely,butgoodforpreventionof
NSAID-inducedgastriculcers
* Gastrostomyfeedingtubesmaybeusedtofacilitatenutritionalmanagementaswellasusedfor
medicationadministrationandfluidsupport.
OnetheoryofprogressionofCKDinvolvesintraglomerularhypertensionintheremainingnephrons.This
isbeneficialinthatitkeepsGFRup;however,theintraglomerularhypertensionmayultimatelyresultin
lossofsurvivingnephronsandprogression.
* Feedingdietscontainingomega-3fattyacidsmaybebeneficialindogs
* Omega-3fattyacidsdecreaseintraglomerularhypertension,maintainGFR,andprolongsurvival
* Anomega-6toomega-3fattyacidratioof3:1to5:1appearstobeareasonableintakeandispresent
inmanyrenalfailurediets
Rubenal
* Anextractofmedicinalrhubarb(Rheumofficinale)
* Proposedtodecreaserenalfibrosis
* InonestudyofcatsofCKD,nobenefitwasfound
RenAvast
* Proprietarymixtureofaminoacidsandpeptides
* Unproveninacontrolled,publishedstudy
ELECTROLYTES
Potassium
* Hypokalemiamayoccurespeciallyincatsdueto
* Anorexia
* Excessiverenalandfecallosses
* Chronicmetabolicacidosis(transcellularshift)
* Activationofrenin-angiotensin-aldosteronesystem(RAAS)
* Clinicalsignsofhypokalemiainclude
* Polymyopathy–classicsignisananimalthatcannotliftitsheadwhilesittingsternally;however,
generalizedweaknessmayoccurmorecommonly
* Worseningrenalfailure
* Anorexia
* Treatment
*
*
*
* Potassium(aspotassiumchloride)maybeaddedtoIVorSQfluids
* Potassiumisoftenpresentinrenalfailuredietsaspotassiumcitrate
* Potassiummaybesupplementedorallyusingpotassiumgluconateorpotassiumcitrate
* Potassiumcitrateprovidesalkalinizationaswellaspotassium
* MaycauseGIupset–relatedtoformulationnottodrug
* E.G.Ifproblemswithliquid–trypowder,granules,ortablets
* Serumpotassiumconcentrationsshouldbemaintainedinmiddletoupperhalfofnormalrange
Sodium
* Changesinserumsodiumconcentrationoccurrarely
* Sodiumretentionoccurswithchronickidneydiseaseresultinginexpansionofextracellularfluid
volumeandhypertension
* Moderatesodiumrestrictionbeneficial
* Decreasefluidretention
* Synergisticwithanti-hypertensivemedications
* ExcessiverestrictionmayactivateRAASpromotingurinarypotassiumexcretion
* Inonestudy,highsaltintake(1.2%)wasassociatedwithincreasingazotemiaincatswithCKD
PHOFBLOOD(ACID-BASESTATUS)
Metabolicacidosisoccurscommonly
* Occursbecauseofretentionoforganicacids,decreasedrenalabilitytoregenerateandreclaim
bicarbonate,decreasedammoniagenesis(ammoniaisabufferandisrenallyexcretedwithacid),
generationofacidsfromcatabolism,
* Highaniongapmetabolicacidosis
* Thereisactuallynoaniongap
* “thebodyisnotabattery”–negativechargedions(anions)mustequalthepositivechargedions
(cations)
* Aniongap=(Na++K+)–(HCO3-+Cl-)
* 0=(unmeasuredcations(UC)+Na++K+)–(unmeasuredanions(UA)+HCO3-+Cl-)
* UA–UC=(Na++K+)–(HCO3-+Cl-)
* UAareacids;bodycannottoleratemuchofachangeinUC
* Withanincreaseinunmeasuredanions->decreaseinbicarbonatewithasubsequentincreasein
aniongap(highaniongapacidosis)
* Withlossofbicarbonate(base)frombody->decreaseinbicarbonatebutanincreaseinchloride
tocompensatewithsubsequentnormalaniongap(hyperchloremicnormalaniongapacidosis)
* Metabolicacidosismaycauseanorexia,hypokalemia,muscleweakness;however,itdoesnot
appeartodirectlyinfluenceprogression
* Serumbicarbonateortotalcarbondioxideconcentrationcanbeusedtoestimateblood
bicarbonatelevels
* Trytomaintainanormalconcentration
* Treatment
* Manyrenalfailuredietscontainpotassiumcitrate,analkalinizingagent
* Becausemetabolismofdietaryproteinresultsinproductionoforganicacids,dietaryprotein
restrictiondecreasesamountoforganicacidthatmustbeexcretedbykidneys
* Alkalinizingagents(potassiumcitrateorsodiumbicarbonate):
* Potassiumcitratemaybepreferredbecauseitprovidespotassiuminadditiontoits
alkalinizingproperties
• Sodiumbicarbonateadministrationresultsinalargesodiumloadthatmayworsenhypertension
andfluidretention,buthasbeenused
§ Proteinuria
• Proteinuriaisnotjustamarkerofglomerulardisease
• Proteinuriaappearstobenephrotoxic
o Stimulatesrenalfibrosisandactivatesinflammation
•
•
*
*
*
*
*
*
*
*
Indicatedwhen:
o CKDIRISstage1:UPC>2.0
o CKDIRISstage2-4:UPC>0.4(cats),>0.5(dogs)
Treatment
o Lowproteindiet(renalfailurediet)
o ACE-I:decreasesintraglomerularpressure
o Omega-3fattyacids
HYDRATION
Polyuriaduetochronickidneydiseaseisoffsetbyacompensatorypolydipsia
Dehydrationoccursifwaterintakedoesnotequalwaterloss
Treatment
* Oral
* Cleanfreshwatershouldbeavailableatalltimes
* Watermaybeaddedtofoodoracanneddietmaybefed
* Flavoringagents,suchasbroth,maybeaddedtofood
* Intravenous
* Inadehydratedanimal,address3partsoffluidtherapy
* Amountneededforrehydration:%dehydratedxBWkg=litersneededforrehydration
* Maintenance:forhealthyanimals:50-70ml/kg/day
* Amountnecessarytoreplacefluidlostasvomitus,diarrhea,orthird-spacedfluid
* Animalswithchronickidneydisease,especiallycats,mayrequiresubcutaneouslyadministered
fluidstomaintainhydrationandpreventdehydration
* Usually75-150mlareadministeredq12-72hr
* Useanon-glucosecontainingelectrolytesolutionsuchaslactatedRinger’ssolution,Ringer’s
solution,etc
* Animplantabledeviceisavailableforlongtermsubcutaneousfluidadministration(GIF-Tube);
however,manycomplications
RETENTIONOFWASTES Eliminationofwastesparticularlynitrogen-containingcompoundsisanimportantfunctionofthekidneys
Reductionofdietaryproteinseemslogical
* Studiesarecontradictorywhetherproteinreductionslowsprogression
* Dietaryproteinrestrictionmaybeassociatedwith
* Decreaseddegreeofazotemia
* Decreasedserumphosphorousconcentration(meat-basedproteinisalsohighinphosphorous)
* Decreasedmetabolicacids
* Decreasedgastricacidity(proteindigestionoccursinstomachandgastricacidsecretionis
stimulated,inpart,bydietaryprotein)
* Twostudies,oneincatsandoneindogs,ofspontaneouslyoccurringrenalfailure,demonstrated
abeneficialeffectfromfeedingarenalfailuredietwhencomparedwithfeedingamaintenance
diet
* Animalslivedlonger
* Episodesofuremiawerelessfrequentandtimetoonsetoffirstepisodewaslonger
* Ownersperceivedqualityoflifewasbetter
* Renalfailuredietsdifferfrommaintenanceinotherways
* But,levelofdietaryproteinfoundinrenalfailuredietsisadequateformaintenanceofadultanimals
isnotlikelytobeassociatedwithproteinmalnutrition
Prebiotics:Feedingdietsthatcontainsolublefibermayredistributeasmallamountofnitrogenintothe
gutforeliminationthusdecreasingtheamountrequiredbythekidneystoeliminate(“nitrogentrapping”)
* Solublefiberpromotesbacterialproliferationinthecolon
* Thisproliferationrequiresnitrogen
*
*
*
*
*
*
*
* Themajorsourceofnitrogenisbloodureanitrogen
* Thus,promotingcolonicbacterialproliferationmaydecreasebloodureanitrogenconcentration
* Theeffectissmallandstudiesarelackingtodemonstrateaneffectonsurvivalorqualityoflife
Probiotics:involveadministeringlivebacteria.Oneformulation,Azodyl,ismarketedas“entericdialysis”.
InonestudyofcatswithCKD,therewasnobenefitandadministrationofAzodylwasnotassociatedwith
decreasingthedegreeofazotemia.
OTHERRENALINSULTS–AVOID
Dehydrationmayprecipitateanacuterenalfailureepisodemakingthechronickidneydiseaseworse
Certaindrugsmaybedirectlynephrotoxicormayworsenrenalfailure
* Gentamicin
* Amphotericin
* Urinaryacidifiers
* Catabolicdrugs–glucocorticoids,immunosuppressivedrugs
* Non-steroidalanti-inflammatorydrugs
* Maybenephrotoxicifgiveninhighenoughdose
* Arenotnephrotoxicwhengivenatrecommendeddosages,butareariskfactorforrenalfailure
* Bydecreasingproductionofprostaglandins,vasodilatoryprostaglandinsmayalsobedecreased
* Ifhypotensionorhypovolemiaoccurs,bloodflowtorenalmedullaiscompromiseddueto
decreasedactivityofvasodilatoryprostaglandinsresultinginischemiaandrenaltubularnecrosis
Riskofbacterialurinarytractinfectionisincreased
* Concentratedurineisadefenseagainstbacterialurinarytractinfection
* Diluteurineoccurswithchronickidneydisease
* Prematureapoptosisofwhitebloodcells
* Clinicalsignsmaybeabsentbecauseofpolyuria
* Mayworsenchronickidneydisease
* Ascendinginfectionfromurinarybladdertokidneys
* Maybepartofcauseofchronickidneydisease
* Prophylacticantibioticsshouldbeavoided
* Mayselectforresistantorganism
* Someantibioticsarenephrotoxic
* Mostantibioticsarerenallyexcretedandsotheirkineticsarealteredbychronickidneydisease
* Administrationmayhavesideeffects–anorexia,vomiting,diarrhea
* Onlyuseantibioticsifabacterialinfectionisdocumented
* Becauseofdiluteurine,bacteriuria,pyuria,andhematuriamaynotbeobvious
* Urinecultureofasampleobtainedbycystocentesisisbest
NEUROENDOCRINEFUNCTION
Renalhyperparathyroidism
* Occurs,inpart,becauseofphosphorousretentionanddecreasedcalcitriol(vitaminD3)metabolism
bythefailingkidneys
* Hyperphosphatemiamayresultinrenalmineralizationandlossofnephrons
* Fibrousosteodystrophy(rubberjaw)
* Hyperphosphatemiaisassociatedwithprogressionofchronickidneydiseaseandofshortened
survival
* Treatment
* Goalistodecreaseserumphosphorousconcentrationto
* <4.5mg/dlwithstage2
* <5.0mg/dlwithstage3
* <6.0mg/dlwithstage3
* Lowerisbetter.
* Serumphosphorousconcentrationmaybedecreasedby:
* Feedingalowphosphorousdiet(renalfailurediets)
* Administeringphosphatebinders
*
•
Administerwithfood–theideaistobindphosphorouswithinthegastrointestinaltract.
Side-effectsareanorexiaandconstipation
* Aluminumhydroxide
* Phosphorousbinderaswellasantacid
* Conventionaldrugofchoice
* Aluminumtoxicityextremelyrareandoccurswithveryhighdosing
* Calciumacetate(PhosLo)
* Phosphatebinderandantacid
* Mayinducehypercalcemia
* Nostudiesindogsandcats
* Sevelamerhydrochloride(Renalgel)
* Non-calciumcontainingphosphatebinder
* Minimalsideeffectsindogsandcats
* Doseisextrapolatedbutbasedontoxicitystudies
• Lanthanumcarbonate(Fosrenol)
• Non-calciumcontainingphosphatebinder
• Appearstobewelltolerated
• Doseisextrapolated
§ Chitosan+calciumcarbonate(Ipakitine)
• Veterinaryspecificphosphatebinder
• Mayinducehypercalcemia
• Onestudyincatsshoweddecreasedphosphorous
• VitaminD
§ HypovitaminosisDhasaroleinrenalhyperparathyroidism
o Kidneysmetabolize25-hydroxyvitaminDtotheactiveform1,25-dihydroxyvitaminD
(calcitriol)byenzyme,1-alpha-hydroxylase
o Calcitrioldecreasesparathyroidhormoneconcentration
o AlthoughrecentstudyindogsdocumenteddecreasedvitaminD3receptorsin
parathyroidglands
o Parathyroidhormonemayhavearoleinclinicalsignsandofprogressionofchronic
kidneydisease,butitiscontroversial
§ Dietaryphosphorousrestrictiondecreasesparathyroidhormonelevels
§ Oraladministrationoflowdosesofcalcitriolmaydecreaseparathyroidhormone
§ Serumphosphorousshouldbenormalizedbeforeadministeringcalcitriolbecauseofrisk
ofhypercalcemiaandincreasingcalciumxphosphoroussolubilityproduct
§ Todate,onlydogsinstageIIIorIVIRISbenefitfromcalcitrioltherapy
o Notbeenshowntobebeneficialincatsatanystage
Hypoproliferativeanemia
• Normocytic,normochromicnon-regenerativeanemiaoccursinmanyanimalswithchronic
kidneydisease.Mayinduceprogressionofdiseaseduetodecreasedbloodflow,stagnationof
blood,oxidativestress,decreasedoxygendiffusion,andinductionoffibrosis
• Causesoftheanemiainclude
• Decreasedproductionoferythropoietin
• Nutritionalimbalancesbecauseofanorexia
• Bloodlossduetouremicgastroenteritis
• Treatmentincludes
• Maintaininggoodnutritionalstatus
• Minimizinggastrointestinalbloodloss
• Stimulatingredbloodcellproductionbybonemarrow
• Anabolicsteroidshaveaminimaleffectinpromotingredbloodcellproduction
• Theymayalsostimulateappetite
• Theymaybeassociatedwithhepatopathy
Erythropoietinanddarbepoetin
• Recombinanthumanerythropoietin(rHuEPO)anditssyntheticanalogdarbepoetin
havebeenusedsuccessfullyindogsandcatswithchronickidneydiseasethatare
severelyanemic
• ManyanimalsreceivingrHuEPOfeelbettereveniftheiranemiadoesnot
improve
• Darbepoetinmaybeassociatedwithfewerincidenceofantibody
productionandisadministeredweeklyandisthehormonereplacementof
choice
• Itisindicatedwhen:
• Packedcellvolumeislessthan15-20%
ThisisbasedonusingrHuEPOwhereantibodyproductionoccurscommonly
Becauseantibodyproductiondoesnotappeartooccurwithdarbepoetin,considerusewhenanemia
beginstodevelop
• Animaldoesnotfeelwellbecauseoftheanemia
• Becauseuremicgastroenteritisiscommon,ironshouldbesupplementedtooffset
theirondeficiencyassociatedwithbloodloss
• Infectionsshouldalsobetreatedtominimizeironsequestration
• TargetoftreatmentistoachieveaPCVof35-45%
• Oncetargetisreached,thefrequencyandamountofdosagecanbeslowly
decreasedtofindlowestamountnecessarytocontrolanemia
• Complicationsinclude
• Irritationatinjectionsite
• Systemicarterialhypertension
• Polycythemia
• Worseningofanemiaafterinitialresponse
• UsuallyassociatedwithantibodyproductionagainstrHuEPO
• Occursin20-40%ofdogsandcats
• Anti-rHuEPOantibodiesmaycross-reactwithnativeerythropoietin
resultinginmoresevereanemiathaninitial
• DiscontinuingrHuEPOusuallyresultsinimprovementofpackedcell
volumetovalueatstartofrHuEPOtreatment
• Thishasnotbeendocumentedwithdarbopoietin
• IfananimalinitiallyrespondstorHuEPOordarbopoietin,butthepackedcell
volumebeginstodecline
• Cross-reactingantibodiesmayhavedeveloped
• Irondeficiencymaybeoccurring
• Treatforuremicgastroenteritis
• Treatanyinfections
• Giveironsupplementationifnotalreadyreceiving
Systemicarterialhypertension
• Occursin65-75%ofdogsandcatswithchronickidneydisease
• PathogenesisincludesactivationofRAAS,activationofsympatheticnervoussystem,increased
ADHduetohypovolemia
• Risks
o AP0(sBP<150mmHg):minimalrisk
o AP1(sBP=150-159mmHg):lowrisk
o AP2(sBP=160-179mmHg):moderaterisk
o AP3(sBP>180mmHg):highrisk
• Resultsindiseasesassociatedwithorganswithsmallvessels
• Eyes–retinalvesseltortuosity,hemorrhage,hyphema,blindness
•
§
§
•
•
•
• Kidneys–proteinuria,progressionofrenalfailure
• Heart–leftventricularhypertrophy,possiblecongestiveheartfailure(leftsided)
• Brain–ischemicencephalopathy,seizures,death
Diagnosisismadebymeasuringarterialbloodpressure
Treatmentincludes
• GoalissBP<150mmHg
• Restrictingdietarysodium–renalfailuredietscontainlesssodiumthanmaintenancediets
• Anti-hypertensivedrugs
• Calciumchannelblockers
• Decreasesbloodpressurebyarteriolarvasodilation
o Moreeffectivefirstlinetreatmentforsystemicarterialhypertensionindogsand
catswithoutproteinuria
o Decreasessystolicbloodpressureby@50mmHg
• Dilatesglomerularafferentarteriole
• AppearstohavefewercomplicationsthanwithACEinhibitors
§ Hypotension
§ GIsigns
• Angiotensinconvertingenzyme(ACE)inhibitors
• DecreasesmetabolismofangiotensinItoangiotensinIIresultinginvasodilationand
decreasedaldosteroneproduction
• Systemicarteriolardilation(viadecreaseinangiotensinII)andpreferentiallydilates
glomerularefferentarteriole
• Complications
§ Mayworsenazotemia–monitor
§ Hyperkalemia
• Benazeprilhasbeenreportedtoslowprogressionofchronickidneydiseaseincats
• 1studyofinducedchronickidneydiseasehasbeenreported
• GFRvalueswerenotdifferentbetweenbenazeprilandplacebogroups
• Thestudylastedonly6months
• Alongtermclinicaltrialfailedtoshowbenefitoverplaceboexceptincatswith
overtproteinuria
o Decreasessystolicbloodpressureby@10mmHg
• Angiotensinreceptorblockers(ARBs)
o InhibitinteractionofangiotensinIIwithreceptor
o SimilareffectsasACE-I
§ Decreasessystolicbloodpressureby@10mmHg
§ Preferentialdilationofglomerularefferentarteriole
§ Complicationsinclude
§ Worseningofazotemia
§ Hyperkalemia
• Aldosteronereceptorantagonists
o Spironolactone
o Promotessodiumexcretionandverymilddiuresis
o Decreasesvascularvolume
o Decreasesbloodpressure–minimaleffect
o Complications
o Dehydration
o Hyperkalemia
o MayworksynergisticallywithACE-IandARBstodecreaseRAASactivation
• Otherdrugsarenotaseffectiveandareonlyusedifmultipledrugsarerequiredtolower
systemicarterialbloodpressure
o Beta-blockers(propranolol,atenolol)
o
•
•
•
•
•
o Alpha-blockers(prazosin)
o Directarteriolarvasodilators(hydralazine)
o Diuretics(furosemide,thiazides,spironolactone)
Renaltransplantation
§ Renaltransplantationcanbedone
§ Moreeffectiveandhighersuccessincatsvsdogs
§ Lessthan20%one-yearsurvivalinonestudy;however,inanotherstudy,a50%survivalatover500days
§ Costis>$10,000andmustadoptdonorpatient
Intermittenthemodialysis
• IntermittenthemodialysismaybeperformedinpatientswithIRISCKDstage4disease
• Requiresperiodictreatmentathemodialysisfacilities
• Interdialytictimeisvariableanddependentonthepatient
• Requiresplacementofalongtermlargeborecentralcatheterthatispronetothrombosisandocclusion
Stemcelltherapy
Mesenchymalstemcells(MSCs)havebeenproposedasanoveltreatmentoptionforthemanagementofCKD.
o MSCsexertpotentanti-inflammatoryandantifibroticeffectsandmaythereforeindirectlyimproverenal
functionbyreducingdisease-associatedinflammationandfibrosisthroughparacrineeffects
o DemonstratedimmunomodulatoryeffectsofMSCsincludeinhibitionoflymphocyteproliferationand
cytokineproduction,suppressionofdendriticcellfunctionandsuppressionofIF-γproductionbynatural
killercells
o InvitrostudieshavedemonstratedthatMSCscanproducegrowthfactors,cytokinesandantiinflammatorymediators,allofwhichcouldhelpmaintainorimproverenalfunctionandsuppressintrarenalinflammation
o TheabilityofMSCstosuppressinflammationappearstobemediatedbothbysecretedfactorsandby
directcontactwithinflammatorycells
o InthemajorityofstudieswithexperimentallyinducedCKDinrodents,administrationofbothadiposederivedandbonemarrow-derivedMSCshasdemonstratedsignificantrenoprotectiveeffects,including
reductionofintrarenalinflammatoryinfiltrate,decreasedfibrosisandglomerulosclerosis.
o Parametersofrenalfunctionandclinicalhealth,includingweight,creatinine,bloodureanitrogen(BUN),
proteinuria,bloodpressureandhematocrithavealsobeendemonstratedtoimproveasaresultofMSC
therapy
o Severalroutesofadministration–intraparenchymal,subcapsular,intraperitoneal,intravenous(IV)–have
beenexplored,andallseemtobeeffective.
o Efficacyisthoughttooriginatefromparacrineeffectsratherthancellengraftmentintothekidney
o MultiplerepeatedinjectionsofMSCsappeartobeevenmoreeffectivethansingleinjections
o AsinflammationappearstobepresentatallstagesofCKDincats,theimmunomodulatoryactionsofMSC
areappealingasapotentialmeansofsuppressingintrarenalinflammationandsubsequentfibrosis.
o MSCtherapymaybeaneffectivenewapproachtoslowtheprogressionofCKDandimproverenal
function.
Inonerandomizedclinicaltrialofcats
o SixcatsreceivedthreedosesofallogeneicMSCculturewithoutadverseeffects.
o Nosignificantchangeinserumcreatinine,bloodureanitrogen,potassium,phosphorus,GFRby
nuclearscintigraphy,UPCorpackedcellvolumewasseenincatstreatedwithMSCs.
o IndividualchangesinGFRwere12%,8%,8%,2%,–13%and–67%intreatedcatscomparedwith16%,
36%and0%inplacebo-treatedcats.
InanabstractpresentationaACVIMin2014
o 19cats(41TX)&15dogs(51TX)
§ 92totalTX
§ 49IA(13cats,36dogs),43IV(28cats,15dogs)
o DX:PLN(5),dysplasia(5),K9CKD(2),FelCKD(19)withobstruction(12/19),AKI(1)
§ MST
• Dogs
o CKD:>245days(2/2stillalive)
o PLN:>227days(3/5stillalive)
o Renaldysplasia:>198days(5/5stillalive)
• Cats
o CKD:>179days(12/19stillalive)
o Obstructivenephropathy:>179days(7/12stillalive)
o ThosewithIRISCKDstage3alone:>213days(6/7stillalive)
SERIALMONITORING
§ Chronickidneydiseaseisprogressiveandthusadynamicdisease
§ Serialmonitoringofbodycondition,bodyweight,thoracicauscultation,bloodpressure,CBCand
serumbiochemicalprofile,urinalysis,andurineculturearenecessarytoadjusttreatment
§ Howoftenananimalshouldbeexamineddependson
§ Howrapidlythechronickidneydiseaseisprogressing
§ Anynon-renalinfluencesthataffectrenalfunction
§ Ownersatisfactionandfinances
• Howcanmedicaltreatmentofchronickidneydiseasebeimproved?
§ Earlydetectionandintervention
§ Chronickidneydiseaseismorecommoninolderanimals;therefore,geriatricscreeningbloodwork
mayidentifyanimalsinearlychronickidneydisease
§ Minimizeoreliminatenon-renalinfluencesonrenalfunction
§ Individualizetreatment
§ Avoidover-treatment
§ Serialmonitoring
• StrategiesfordiagnosisofCKDusingcreatinine
§ Normalrangescanbemisleading
§ UseIRISrecommendations(cats=1.6mg/dl;dogs=1.4mg/dl)
§ Changeof0.2mg/dlinahydratedpatientissignificant
§ Markedreductionsinkidneyfunctioncanbeassociatedwith“normal”serumcreatinine
concentrations
§ Serialmonitoring
• Observations
§ Atsomepoint,thediseaseprogresses
§ Earlymodificationofrateofprogressionhasmarkedimplication
§ EarlydiagnosisofCKDhasprofoundimplications
§ Educateownersearly
• Changesinwaterintake,urinevolume,foodintake,bodyweight,activity,behavior
• Decreasedbodyweightandbodycondition,smallordissymmetricalkidneys,largeurinary
bladder(polyuria?),hypertension
• Urinalysis–anextremelyimportanttool
• Whenshoulddietbechangedinananimalwithchronickidneydisease?
§ Dietarymodificationcanoffsetmanydeficienciesandexcessesthatoccurwithchronickidneydisease
§ Dietarymodificationincludesmorethanjustdietaryproteinrestrictionasrenalfailuredietsaremore
caloricallydense,maycontainomega-3fattyacids,maycontainsolublefiber,lowphosphorous,low
sodium,potassiumreplete,alkalinizing,andwatersolublevitaminreplete
§ Ibelievedietshouldbechangedwhenananimalisdiagnosedwithchronickidneydisease
§ Renalfailuredietsareusuallyindicatedatsomepointinmanagementofdogsandcatswithchronic
kidneydisease
§ Renalfailuredietsarenotassociatedwithdeficiencies
§ Renalfailuredietsmaybetoleratedbetterifintroducedwhiletheanimalfeelsgoodandiswillingto
acceptadietarychange
§ Renalfailuredietsmaydeceaseuremicepisodesandprolongsurvival
DRUGSANDDOSAGESMENTIONEDINTHESEPROCEEDINGS
Class
Drug
Dosagefordogs(D)orcats(C)
H2blocker
Famotidine
D,C:1-2mg/kgPOq12h
Ranitidine
D,C:1-2mg/kgPOq12h
Gastroprotectant
Sucralfate
D:0.5-1gmPOq8-12h;C:0.25-0.5gmPOq8-12h
Protonpump
Omeprazole
D,C:0.7-2mg/kgPOq12-24hr
inhibitor
Esomeprazole
D,C:0.7mg/kgPOq12-24hr
Serotonin
Mirtazapine
D:15-30mgPOq24h;
antagonist
C:1.875-3.75mgPOq72h-cangiveq48hwithCKD
Ondansetron
D,C:
1)0.5mg/kgIV;then0.5mg/kg/hrconstantrateinfusion
2)0.1-0.2mg/kgIVslowlyq6-12hprn
3)0.5-1mg/kgPOq12-24h
Dolasetron
D,C:0.6-1mg/kgPO,IVq12-24h
NK-1inhibitor
Maropitant
D,C:2-4mg/kgPOq24h
PGE2analogue
Misoprostol
D:2-7.5mcg/kgPOq8-12hr;C:5mcg/kgPOq8hr
Medicinerhubarb
Rubenal
D:<3kg:37.5mg;3-6kg:150mg:6-12kg:150mg;13-25kg:
300mg;26-45kg:600mg;>45kg:900mgPOq12h
C:<2kg:37.5mg;>3kg:75mgPOq12h
Aminoacids/
RenAvast
C:1capsulewithfood
peptides
Potassium
Potassiumcitrate
D,C:initial:75mg/kgPOq12h
Probiotics
Azodyl
D,C:<2.5kg:1capsulePOq24h;2.5-4.5kg:1capsulePOq12h;>
4.5kg:2capsulesPOinAMand1capsulePOinPMwithfood
Visbiome
D,C:1/10packetper4.5kgPOq24hwithfood
Phosphatebinder
Aluminumhydroxide
D,C:15-45mg/kgPOq12hwithfood
Calciumacetate
D,C:60-90mg/kgPOq12hwithfood
Sevelamer
D,C:400-1600mgPOq12hwithfood
hydrochloride
Lanthanumcarbonate
D:5-20mg/kgPOq12h
C:1ml(1pump)POq12h(Renalzin)
Chitosan+calcium
D,C:1g/kgPOq12h
carbonate
3-5kg:1scoop;10kg:2scoops;15kg:3scoops;20kg:4scoopsPO
q12h(Ipakitine)
VitaminD
D,C:initial:2-2.5ng/kgPOq24h;maximum:5ng/kgPOq24h
Erythropoietin
Erythropoietin
D,C:100ug/kgSQ3X/weekinitially
Darbepoetin
D,C:1.5-1.0ug/kgSQ1X/weekinitially
Calciumchannel
Amlodipine
D:0.1-0.4mg/kgPOq24h;C:0.625-1.25mgPOq24h
blocker
ACE-I
Enalapril
D,C:0.25mg/kgPOq12hinitially
Benazepril
D,C:0.25mg/kgPOq12hinitially
Angiotensin
Losartan
D,C:1mg/kgPOq12h($8//mofor25lbdog)
receptorblocker
Azilsartan
D:0.1-1.0mg/kgPOq12h($140/mofor25lbdog)
Irbesartan
D:5mg/kgq12-24h($115/mofor25lbdog)
Telmisartan
D,C:5-10mg/kgPOq24h($40/mofor25lbdog)
Valsartan
D:80-160mgPOq24h($60-100/mofor25lbdog
Aldosterone
Spironolactone
D,C:1-4mg/kgPOq12h-24h
receptorblocker