HarvardMedicalSchoolandMassachusettsGeneralHospitalInternalMedicineComprehensiveReviewandUpdate

Course:2017

UpdateinManagementofChronicKidneyDisease,

includingESRDDavidSteeleMD

RenalUnitMassachusettsGeneralHospital

BostonMA.

Ihavenoconflictsofinteresttodeclare

Question

• ThemostcommonreasonforlatereferralofpatientswithchronickidneydiseasetoNephrology:a. PerceptionthatNephrologistsnegatively

perceivepriorcare:b. Lackofcommunicationfromnephrologists:c. Lackofspecificcriteriaforreferral:d. Latepresentationorreluctancebypatient:e. Fearoflosingpatienttonephrologist:

Answer

• ThemostcommonreasonforlatereferralofpatientswithchronickidneydiseasetoNephrology:a. PerceptionthatNephrologistsnegatively

perceivepriorcare:43%b. Lackofcommunicationfromnephrologists:37%c. Lackofspecificcriteriaforreferral:31%d. Latepresentationorreluctancebypatient:23%e. Fearoflosingpatienttonephrologist:19%

Campbell et al. Dialysis and Transplantation. 1989;18:660-86

Aims

• GatherasenseofthedemographicsandnaturalhistoryofChronicKidneyDisease(CKD)

• UnderstandtheimpactofCKDonthepatientandit’sassociatedco-morbidities

• ReviewESRDmanagementoptionsincludingmedicalmanagement

CKDandESRDDemographicsandClinicalOutcomes

• 678,383patientswithESRD(2014)– 63.1%receiving

hemodialysis,– 6.9%peritonealdialysis– 29.6%kidneytransplant

• ESRDincidencerateincreasing1-3%pa

• MortalityrateforESRDonDialysis~20%

• HospitalizationratesforESRDonDialysis– ~2.3hospstaysperyear– ~9-15hospdaysperyear

USRDS ADR 2017

DistributionofCostsGeneralMedicarePopulationCKDandESRD

USRDSADR2010

Combined costs to Medicare for CKD and ESRD are on par with the other two large chronic disease categories: Diabetes and CHF

DefiningChronicKidneyDisease(CKD)

DM40%

HTN25%

Glom Dz10%

Non Glom Dz5%

Tx Loss5%

Urological2%

Other13%

• Kidneydamageof>3months

• GFR<60ml/min/1.73m2• CKDresultsfrommanypathophysiologicallydistinctdiseaseswhichshareacommonnaturalhistory

• CKDshouldbestagedusingeGFR(egMDRD)

StagesofChronicKidneyDisease,RiskforProgression,andRecommendationsforMonitoringeGFR

AdaptedfromKDIGO.KidneyInt Suppl. 2013;3:63

• KDIGO(KidneyDiseaseImprovingGlobalOutcomes)guidelineemphasizesAlbuminuria asanadditionalriskfactorforCKDprogressionandcardiovasculardisease

• NephrologiststypicallymanageadvancedCKD;PrimaryCareCliniciansmayneedto:– educatepatientsabout

treatmentrecommendations– bethefirsttodetect

progressionoronsetofcomplications

– managepatientswhodeclinenephrologyreferral.

Question

• TheTromsøstudylookedatthenaturalhistoryofCKDinapopulationof58000patientsinScandinavia.3047patientswerefoundtohaveaGFRbetween30and60ml/min.Patientswerefollowedfor10yearsandtherateofprogressiontoESRDwas:

A. 4%B. 10%C. 12%D. 25%

Answer

• TheTromsø studylookedatthenaturalhistoryofCKDinapopulationof58000patientsinScandinavia.3047patientswerefoundtohaveaGFRbetween30and60ml/min.Patientswerefollowedfor10yearsandtherateofprogressiontoESRDwas:

A. 4%B. 10%C. 12%D. 25%

LongitudinalFollow-upandOutcomesAmongaPopulationWithChronicKidneyDiseaseinaLargeManagedCareOrganization

45.7

24.319.510.2

19.9

1.21

0

27.8

64.263.3

74.8

6.610.316.214.9

0%

20%

40%

60%

80%

100%

Stage 1 Stage 2 Stage 3 Stage 4

% P

ts

DisenrolledEvent FreeRRTDied

27998 patients identified with GFR < 90ml/min and followed for 5 years

Arch Intern Med. 2004;164:659-663

StrategiesforCaringwithPatientswithCKD4

• DelayProgression– ACEInhibition– Manage

metabolicabnormalities

– MinimizeAKIrisk

– Reviewdietaryoptions

• ManageComorbids– Cardiovascular

risk– Anemia

management– MetabolicBone

DiseaseManagement

• PrepareforESRD– Isolatehighrisk

populations– Patient

education– Referto

Nephrology– Preparefor

angioaccess– ReviewMedical

Managementoptions

ProgressionofCKD- Angiotensin IIeffects

• AngiotensinII– Hemodynamiceffects

• SinglenephronincreasedGFR

• Increasedintraglomerularpressure

– NonHemodynamiceffects

• Inflammationandoxidativestress

• Cellularhypertrophyandproliferation

SecondaryFocalSegmentalGlomerulosclerosis

HyperfiltrationofremaininghealthyNephrons

PrimaryInjurywithlossofNephron mass

DeclineinGFR:ACEIandARBuseinType1andType2DiabeticsLewisetalNEJM329(20),1993

BrenneretalNEJM345(12),2001

0

2

4

6

8

10

GF

R d

eclin

e m

l/min

/yr

Placebo Losartan

The Renaal Study

0510152025303540

GFR

dec

ent p

er

year

%

Group Creat>1.5

Captopril Study Group

PlaceboCaptopril

Reduction in risk of doubling serum creatinine•Captopril Study (Lewis) - 48%•Renaal Study (Brenner) - 25%

ACEI/ARB’sinCKD

• ACEIorARBareindicatedfordiabeticpatientswithuAlb/Creat ratio>0.03(microalbuminuria)

• ACEIorARBareindicatedforCKDpatientswithuAlb/Creat ratio>0.5(overtproteinuria)

1. Tolerateasmall(+/- 25%)riseinserumcreatinine

2. AttempttomanageHyperkalemia withoutwithdrawalofACEI/ARB:– DietaryKrestriction– Kayexalate prn– Loopdiuretics;Fludrocortisone

3. UseARBinpatientsintoleranttoACEI(cough)

DietandLifestyleDiet

• CKDpatientsshouldreceiveexpertdietaryadviceifavailable

• Lowerproteinintaketo0.8g/kg/dayinpatientswithGFR<30ml/min

• Avoidhighproteinintake(>1.3g/kg/day)inadultswithCKDatriskofprogression.

• TargetHbA1cof<7.0%(extendedabove7.0%inindividualswithcomorbidities orlimitedlifeexpectancyandriskofhypoglycemia)

• Lowersaltintaketo<2gperdayofsodium

Lifestyle

• Undertakephysicalactivity– 30minutes5timesperweek

• Achieveahealthyweight– BMI20to25

• Stopsmoking• AvoidNSAID’s

Vaccinations• AnnualInfluenza• Pneumococcalvaccineq5

years• Hep Bforstage5CKDand

likelyprogressiontoHDKidney International Supplements (2013) 3, 5–14

CKDpredisposeshospitalizedpatientstoAcuteRenalFailure

USRDS ADR 2009

• CKDincreasestheriskofAKIsevenfoldinhospitalizedpatients.

• InAKIpatientswithCKD,thehazardsfor:– ESRD85.0– Death3.1

(inAKIpatientswithnoCKD,hazardsare11.7and2.5,respectively)

These are the patients who “crash” onto dialysis

NephroPharmacologyRenally doseallmedicationsandmonitoreGFR anddruglevelsasindicated.– ReconsiderdosewithanysignificantchangeineGFR andreviewmedicationsregularlyforcontinuedappropriateness.

– ProlongedNSAIDuseshouldbeavoidedinearlystageCKD.– Counselpatientstoconsultaphysicianorpharmacistbeforeusingover-the-countermedicationsorsupplements.

ConsidermonitoringeGFR morefrequentlyandholdingrenally clearedandpotentiallynephrotoxicmedicationsduringacuteillnessorintheperioperativeperiod.

ImagingStudiesIodinatedContrastStudies:• Avoidhighosmolar agents• Uselowestpossiblecontrastdosecompatiblewithcompletestudy• Withdrawpotentiallynephrotoxic agentsbeforeandafterthe

procedure• Giveadequatehydrationwithsalinebefore,during,andafterthe

procedure• MeasureGFR48–96hoursaftertheprocedureGadolinium-basedcontraststudies:• DonotusegadoliniuminPtswithGFR<15ml/min/1.73m2(unless

thereisnoalternativeappropriatetest)• ForptswithaGFR<30ml/minuseamacrocyclic chelate

preparationBowelpreparation:• Avoidoralphosphate-containingbowelpreparationsinptswith

GFR<60ml/minduetoriskofphosphatenephropathyKidney International Supplements (2013) 3, v

CardiovascularDiseaseinPatientswithChronicKidneyDisease

AbboudHandHenrichW.NEnglJMed2010;362:56-65.

LipidManagement• Statins decreaseriskforCVD

eventsanddeathby20%inptsnotondialysis.

• PtswithtraditionalCVrisks(diabetes,coronarydisease,priorstroke,orincreased10-yearrisk)shouldreceivestatin therapyaccordingtocurrentguidelines

• Intheabsenceoftraditionalriskfactors,stronglyconsiderstatintherapyif:– Age>50years– Historyoftransplantation

(cyclosporineincreasesserumlevelsofsomestatins)

Adapted from Tonelli, et al Ann Int Med. 2014; 160:184

MGH POCI Management of Advanced CKD and It’s Complications. Authors: Mary H. Hohenhaus, MD; Shana Birnbum MD. Specialty Reviewer: David J.R. Steele, MD

ManagementofHTNJNC8:• Inthegeneralpopulation

aged≥60years– TreatBP>150/90

• Inthegeneralpopulation<60years– TreatBP>140/90

• Inthepopulationaged≥18yearswithCKD– TreatBP>140/90anduseACEI

orARB

KDIGOGuidelines:• Indiabeticandnon-

diabeticadultswithCKDandwithurinealbuminexcretionof>30mg/24hours– TreatBP>130/80anduse

ACEI/ARB(2Dlevelofevidence)

BenefitsofTreatingHypertensionandCKD

BakrisGLet.al.AmJKidneyDis,Sept.2000

AnemiaManagement

• CheckhemoglobininpatientswitheGFR <45ml/min

• ExcludeothercausesofanemiabeforeattributingtoCKD

• Ifthepatientislikelytobenefitintermsofqualityoflife,considerreferralforESAcandidacyifHb <9g/dl

StudiesofAnemiaManagementandtheuseofErythropoetininCKD

NormalHct StudyBesarab Aetal.NEngl JMed1998;339:584-590

183deathsand19 nonfatalMI’sinnl-Hct groupand150deathsand14nonfatalMI’sinlow-Hctgroup(RR1.3;95%CI,0.9to1.9).Studyhalted.

Ptsinnl-Hct grouphadadeclineintheadequacyofdialysisandreceivedmoreIVirondextran.

CHOIRStudyAjaySinghetal.NEngl JMed2006;355:2085-98.

125events(Death,MI,CHF,Stroke)inthehigh-Hb groupvs97eventsinthelow-Hb group(HR,1.34;95%CI,1.03to1.74;P=0.03).

Improvementsinthequalityoflifeweresimilarinthetwogroups.

CREATEStudyDrueke etalNEngl JMed2006;355:2071-84

Noeffectonfirstcardiovascularevent

Generalhealthandphysicalfunctionimprovedsignificantly(P=0.003andP<0.001)inhigh Hb group.

TREATStudyMarcPfeffer etalNEngl JMed2009;361:2019-32

Deathoracardiovasculareventin632ptsinRxgroupvs 602ptsinplacebogroup(P=0.41)

Fatalornonfatalstroke in101ptsinRxgrp vs 53inplacebogroup(P<0.001).

VascularBiologyisabnormalinCKD.Coronary-ArteryCalcificationinYoungAdultswithEnd-StageRenalDisease

UndergoingDialysis(NEnglJMed2000;342:1478-83.AIN May1998Vol128:10;839-847)

1. Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis.

2. The mean serum phosphorus, the mean calcium-phosphorus ion product, and the daily intake of calcium were higher among the patients with coronary-artery calcification

Sample electron-beam computed tomographic scan showing calcification of the left anterior descending coronary artery (thick arrow) and the aortic root (thin

arrow).

MineralMetabolisminCKDMeasureserumcalciumandphosphateifeGFR <45ml/min

Offerbisphosphonates forthepreventionandtreatmentofosteoporosisinpatientswitheGFR >30ml/minonthesameindicationsasforallotherpatients

AvoidHyperphosphatemia

CorrectNutritional25OH Vit DDeficiency

TreatSecondaryHyperparathyroidism

Restrictdietaryphosphateintake

Usephosphatebinderswhenindicated

-Calciumbased:CaCO3;CaAcetate

-NonCalciumBasedSevelamer;(AlOH3)

Supplementwith25OHVit Diflevel<30ng/LEg:Ergocalciferol50000u/weekfor12weeks

Supplement1,25VitaminD(Calcitriol)accordingtoPTH level

TreatwithCalcitriol orequivalentif:

- PTH>70ng/LinCKD3- PTH>120ng/LinCKD4

PreparingforESRD:PatientandPhysicianAwareness

PatientawarenessPhysicianAwareness

7.9% 12.5% 9.9% 11.4%

0%

20%

40%

60%

80%

100%

Proteinuria Abn sCrDMHTN

0

10

20

30

40

50

60

eGFR of 30-59 eGFR of 15-29

Per

cen

t R

epor

t B

ein

g A

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H

avin

g W

eak

or F

ailin

g K

idn

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Men

Women

Coresh, et al., 2007

McClellan,AJKD1997,29:368-75

%Patients under Nephrology CarePrior To Dialysis Start

Peer Kidney Initiative

PreparingforESRD:TheTimingofSpecialistEvaluationinChronicKidneyDisease;

effectonMorbidityandMortality

1.81.5

1

0

0.5

1

1.5

2

Haza

rd R

atio

for

Deat

hLate Early<4 4-12 >12

Months before initiation Dialysis

Rateofdeathmeasuredfrominitiationofdialysistoaverageof

2.2yearsfollowup

KinchenetalAnnInternMed.2002;137:479-486.

4.8

29.7

0

5

10

15

20

25

30

> 6 M onth s < 15 D ay s

e g th of stay (d ay s)

Jungersetal,JAmNephrol1997;8:140A

Effectoftimingofreferralonlengthofstayattheinitiationofdialysis

PrincipleofHemodialysis

Advantages of Timely Referral inPatients with Progressive CKD1. Improves patient preparation for RRT.2. Greater use of permanent vascular access.3. Avoidance of emergent hemodialysis initiation.4. Greater utilization of transplantation and self-

care dialysis (i.e., peritoneal dialysis or home hemodialysis).

5. Management of medications which may help to delay the need for RRT.

6. Gives the nephrologist adequate time to counsel patients through this challenging transition in their lives.

Relative Risk P valueof death

Diabetics:AVF 1.00PTFE 1.39 0.0004Catheter 1.49 0.0004

Non-Diabetics:AVF 1.00PTFE 1.09 0.26Catheter 1.72 0.0001

Benefits of a Fistula

ThrombosisfollowingPICCplacement

Figure1.A38-year-oldasymptomaticwoman1dayafterPICCplacementwithinadvertentremoval.Venographydemonstratesnon-occlusivethrombusinabrachialvein

Allenetal,JIVR,2000

• Identify CKD stages 3,4 or 5, including current hemodialysis, peritoneal dialysis or transplant patients as a special population when planning central venous access

• Plan appropriate venous access in these cases– dorsal hand veins for

phlebotomy– internal jugular veins are

preferred for central venous access

– external jugular veins are acceptable alternative

– Avoid any catheters in subclavian veins

PeritonealDialysis• Lessthan8%ofprevalentESRD

patientsintheUSareonPD;significantlylessthaninotherdevelopedcountries

– subtledifferencesinpracticepatterns– unintendedfinancialconsiderations

• MedicaloutcomedatewouldseemtofavormoreutilizationofPD

– Improvedmortality

• Mosthomedialysisunitsaresmall– somehaveminimalclinicalexperience– consolidationofPDprogramsmay

needed.

Burkhart J, CJASN 2009 Dec;4 Suppl 1:S125-31

Multidisciplinary pre-dialysis programs increase the proportion of patients initiating dialysis with PD.

Ribitisch et al Peritonal Dial Int 2013 Jul-Aug;33(4):367-71

KidneyTransplantationKeyConcepts•Kidneytransplantationisthemostcost-

effectivemodalityofrenalreplacement.•Transplantedpatientshavealongerlifeand

betterqualityoflife.•Earlytransplantation(before[pre-emptive]or

within1yearofdialysisinitiation)yieldsthebestresults.

•Livingdonorkidneyoutcomesaresuperiortodeceaseddonorkidneyoutcomes.

•Earlytransplantationismorelikelytooccurinpatientsthatarereferredearlytonephrologists.

•ReferfortransplantevaluationwheneGFR <20mL/min/1.73m2.

Timingoftheinitiationofdialysis:EarlyversusLateStart.

• 828patients• EarlyStart:GFR10-14ml/min;LateStart:

GFR5-7ml/min• 76%oflatestartpatientsinitiatedHDwith

GFR>7.0ml/min• Considerdialysisinitiationbefore/when

oneormoreoffollowingispresent– symptomsorsignsattributabletokidney

failure(serositis,acid-baseorelectrolyteabnormalities,pruritus);

– inabilitytocontrolvolumestatusorbloodpressure;

– progressivedeteriorationinnutritionalstatusrefractorytodietaryintervention;

– cognitiveimpairment.• OftenoccursintheGFRrangebetween7

and10ml/min

Question• A78yearoldmanwithapriorhistoryofmyocardial

infarctionandCHFandwithstage5CKDisseenintheoffice.Hiswifeandsonaccompanyhimandadiscussionregardingdialysisoptionsensues.Whichstatement(s)iscorrect?

a. Patientsoverage75representthemostrapidlyincreasinggroupenteringtheUSESRDprogram

b. Agehasbeenshowntobeariskfactorforpooroutcomesindialysispatients

c. Patientsoverage75withcardiovascularcomorbidity benefitfromtheearlyinitiationofdialysis

d. LivingdonorrenaltransplantwouldhisbestoptionforESRDtreatmentandshouldbepursued.

Answer• A78yearoldmanwithapriorhistoryofmyocardial

infarctionandCHFandwithstage5CKDisseenintheoffice.Hiswifeandsonaccompanyhimandadiscussionregardingdialysisoptionsensues.Whichstatement(s)iscorrect?

a. Patientsoverage75representthemostrapidlyincreasinggroupenteringtheUSESRDprogram

b. Agehasbeenshowntobeariskfactorforpooroutcomesindialysispatients

c. Patientsoverage75withcardiovascularcomorbiditybenefitfromtheearlyinitiationofdialysis

d. LivingdonorrenaltransplantwouldhisbestoptionforESRDtreatmentandshouldbepursued.

IncidenceofESRD:ByAge- theageingofthedialysispopulation

Incident CasesIncidence Rates

USRDS ADR 2014

FunctionalStatusofElderlyAdultsbeforeandafterInitiationofDialysis

•3702nursinghomeresidentsintheUnitedStates•InitiateddialysisdialysisbetweenJune1998andOctober2000.•Atleastonemeasurementoffunctionalstatuswasavailablebeforedialysis.•FunctionalstatuswasmeasuredbyassessingthedegreeofdependenceinsevenADL’s(ontheMinimumDataSet–ActivitiesofDailyLiving[MDS–ADL]scaleof0to28points,withhigherscoresindicatinggreaterfunctionaldifficulty).

TamuraetalNEnglJMed2009;361:1539-47.

Acomparativesurvivalstudyofpatientsover75yearswithchronickidneydiseasestage5

Kaplan–Meiersurvivalcurvescomparingthedialysisandconservativegroups(P<0.001).

Kaplan–Meiersurvivalcurvesforthosewithhighcomorbidity(score>2),comparingdialysisandconservativegroups

MurtaghetalNephrolDialTransplant(2007)

ConservativeManagementofStageVCKD

• Conservativemanagementshouldbeanoption

• Itshouldbesupportedbyacomprehensivemanagementprogram.

• Itshouldbeavailabletopeopleandfamiliesthrougheitherprimarycareorspecialistcareaslocalcircumstancesdictate.

• Thecomprehensiveconservativemanagementprogramshouldinclude:– protocolsforsymptomand

painmanagement,– psychologicalcare,spiritual

care– culturallysensitivecarefor

thedyingpatientandtheirfamily(whetherathome,inahospiceorahospitalsetting)

– provisionofculturallyappropriatebereavementsupport.

Kidney International Supplements (2013) 3, 5–14

Conclusions• KidneyDiseaseiscommonandmanagementiscomplicated• ThemajorityofpatientswithCKDhavenonprogressive

disease• Cardiovasculardiseaseisamajorco-morbidity• ForpatientswithprogressiveCKDcarestrategiesshouldbe

initiatedearlytoimprovelongtermmorbidityandmortality• Ateamapproachisrequired• Pre-planningforrenalreplacementtherapiesisnecessaryin

thosewithprogressivedisease