Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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