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TUBERCULOSIS AND CHRONIC RENAL FAILURE unior Resident Pulmonary Medicine

Tuberculosis And Chronic Renal failure

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TUBERCULOSIS

ANDCHRONIC RENAL

FAILURE

unior Resident Pulmonary Medicine

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Magnitude Of The Problem:

Patientswithrenaldiseaseareatincreasedriskoftuberculosis(TB).Thisis

trueforallpatientswithchronickidneydisease(CKD),30timeshigher

prevalenceofTBinpatientswithCRF.YuanFH,GuanLX,ZhaoSJRenalFal2005;27:149-53

Ithasbeenestimatedpatientsundergoingdialysishave10to12foldhigher

riskofdevelopingTBcomparedtogeneralpopulationRutskyEA,RostandSGArchInternMed1980;140;57-61

TheincidenceofTBinIndianpatientsreceivingMaintenanceHemodialysis

hasbeenreportedtobe3.7to13.3percent.NarulaASetalIndianJNephrol1991;1;67

IncidenceofTBinrenaltransplantrecepientshasrangedfrom1to4%in

NorthernEurope,0.5-1%inNorthAmericaandnearly5to10%inIndia.McWhinneyN,KhanO,WilliamsGBrSurg1981;68:408-11

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Why increased incidence of TB in CKD patients

:Pathogenesis 

UREMIA :

 Acquiredimmunodeficiencystateleadingtoexcessivemorbidityand

mortalityrelatedtoinfections.

Granulocytefunctionslikechemotaxis,adherenceandphagocytosisare

defective.

DecreasedInterleukin2(IL2)productionbyactivatedTHelperCells

 Adefectinthecostimulatoryfunctionofantigen-presentingcells,anda

persistentinflammatorystateofmonocytes,whichiscausedbythe

uremiaperse,aswellasbythedialysistreatment

ChatenoudL,Descamps-LatschaB:Immunologicaldisturbancesinuremia.In:MassrySG,

GlassockRJ(eds).TextbookofNephrology,4thed.Philadelphia:LippincottWilliams&

Wilkins,2001:1433 – 1438

Thehostresponseagainstintracellularpathogens,includingMycobacterium

tuberculosis,isdeterminedbythetype1helperT-cellresponsewiththeinvolvementof

interleukin(IL)-12,resultinginincreasedproductionofinterferon(IFN)-c

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HEMODIALYSIS :

Leucocytechemotaxishasbeenshowntomarkedlydiminished

Conventionalcellulosemembranecausesalternatecomplementpathway

leadingtochangesingranulocytecelladhesionmoleculesCD11b,CD18

andLselectin,thiscorrelatewithleucopenia

Impairmentofphagocytosisisoftenencounteredwithcuprophane

membrane

WoeltjeKF,MathewA,RothsteinM,SeilerS,FraserVJ:Tuberculosis

infectionandanergyinhemodialysispatients.AmJKidneyDis31:848 – 852,1998

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IMMUNOSUPPRESSIVE THERAPY :

Immunosuppressionwithtacrolimusormycophenylatemofetil

is,however,associatedwiththedevelopmentofTBearlierinthepost-transplantperiodandinyoungerpatients.

PredisposingtoinfectionasCellmediatedandhumoral

immunitygotaffected

Other factors which might contribute to the decreased

immunity are

Malnutrition,

Vitamin D deficiency , andHyperparathyroidism

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Clinical Features

 Aninsidiousonsetofsymptoms,withfever,anorexia,andlossofweight

beingthemaincomplaints,mimickinguremicsymptoms.

Pienetal.foundfeveroccurringinameanof72%ofthecases(range29 – 

100%),malaiseinameanof69%(range29 – 100%),andweightlossinameanof54%(range10 – 100%).

However,coughandhemoptysis,classicsymptomsofTBinthegeneral

population,arelessfrequentlyreportedindialysispatients(mean22%of

cases;range5 – 71%)

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Clinical Presentation of Tuberculosis

during Maintenance Hemodialysis

•Malesnearlyaffectedtwiceascommonlyascomparedtofemales

•MajoritydevelopTBpriortoinitiationorwithinshortperiodfromthe

beiginingofMHD,atimewheneffectofuraemiaonimmunestatusisstill

pronounced

•ConstitutionalsymptomsattributabletoTBhavebeenreportedin30to92

percentpatientsinvariousseries

•Headache,chillsandshortnessofbreathwerelesscommon(lessthan

30%)

• Almost15%presentedwithPyrexiaofUnknownOrigin

•Malhotraetal(1981)pleuraleffusioninalmost50%ofcasesinonestudy.

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•LungisthemostcommonsiteofinvolvementinpatientsonMHD,Pulmonary

TBrangedfrom40to92%

•LymphNodeinvolvementhasbeenfoundtobemostcommonextrapulmonary

siteofTBonMHD15to30%

Otherextrapulmonaryinvolvementinclude Abdomen

Meninges

BoneandJoints

•Disseminated/MiliaryTBrangedbetween10to15%

•TuberculosisPeritonitishasbeendescribedinpatientsonContinuous

 AmbulatoryPeritonealDialysis

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Clinical Presentation of Tuberculosis

following Renal Transplantation

Tuberculosisin

RenalTransplant

Patients

TBinPretransplant

phase..Havingpost

RTphasetoo

TBfirsttime

followingRT

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PatientwhodevelopTBfollowingRTareusuallyyounger.Malearemore

oftenaffected.

PasthistoryofTBhasbeenreportedin5.6to8.9%patientsinstudies

reportedinIndia.

ConstitutionalSymptomsaremoreoftenencounteredinRTpatientsthan

inpatientsonMHD

LungismostcommonsiteRTpatientswhodevelopfollowedbyabdomen,pericardium,thalamus,boneandjoints

MiliaryTBhasalsobeenreportedin7to36%ofRTpatients

PUOpresentationisassociatedmorecommonlywithRTpatients

 AbdominalTBmorecommonlyduringdialysis

NeurologicalTBmorecommonaftertransplantation

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Diagnosis

ThediagnosisofTBisbasedonthefindingofan acidfast bacilli-positive smear,

positive culture of M. tuberculosis, and typical histopathologic findings.Eff ortsshouldbemadetoobtainappropriatematerialsforculture,whichshould

includesensitivitytesting

ThediagnosisofTBishamperedbythecommonoccurrenceofanegative

purifiedproteinderivative(PPD)(Mantoux)skintest,whichwasfoundin40 – 100%ofthecases.

Routinebloodinvestigationsincludingrenalfunctiontestandsugarmonitoring

tokeepcheckonrenalfunctionanddiagnoseandkeepunderlyingpathology

underscanner.

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Paradoxically,anddespitethehighrateofanergytointracutaneously

administeredantigensinuremicpatients,highratesofpositiveMantouxtests(6.1 – 19%)havebeenfoundinroutinescreeningofdialysispatients

withoutahistoryoforactiveTB.

Thus,duetothefrequentextrapulmonarypresentationandnonspecific

symptomatology,a high index of suspicion is required, coupled with a

need for invasive procedures, including liver, bone, lymph node, andperitoneal biopsies

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Recommendations

1.Allpatientswithchronickidneydisease(CKD)consideredatriskfor

tuberculosis(TB)shouldhaveahistoryofpriorTBorTBcontactsought,anyhistoryofpriorTBtreatmentchecked(includingdrugstakenand

treatmentduration),anappropriateclinicalexamination,achestx-ray

2.AnypatientwithCKDwithanabnormalchestx-rayconsistentwith

pastTB,orprevioushistoryofextrapulmonaryTBbutwhohaspreviouslyreceivedadequatetreatmentshouldbemonitored

regularlyandconsideredforreferraltoandassessmentbya

specialistwithaninterestinTB,eitherathoracicorinfectious

diseasesphysician.

3.Thedecisiononchemoprophylaxisregimenshouldbemadebythe

thoracicorinfectiousdiseasephysicianafterdiscussionwithboththe

patientandrenalteam

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DIAGNOSIS OF LATENT TB INFECTION

ThediagnosisofLTBIisbasedoninformationgatheredfromthemedical

history,TSTorIGRAresult,chestradiograph,physicalexamination,andincertaincircumstances,sputumexaminations.

TimingofscreeningForpatientswithCKD,thereisnoevidenceonwhenorhowtoscreenfor

LTBI.ScreeningallpatientswithadvancedCKDorevenonlythoseonhaemodialysisorperitonealdialysiswouldbetime-consuming,expensiveand

unlikelytobecost-effective

Thecurrentpracticeinmostrenalunitsistogiveprophylaxistoallat-risktransplantpatientswithoutassessment.

 Asignificantproportionofpatientswillbereceivingprophylaxiswithout

evidenceofLTBI.ChemoprophylaxiscouldbeofferedtothosewithLTBIbefore

transplantation,precludingtheneedforpost-transplantprophylaxis.

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Method of screening

 AllpatientswithCKD,onhaemodialysisorCAPDandpriortorenal

transplantationshouldhaveachestx-rayandabnormalitiesinvestigated.

Mostpatientswillhavenormalx-raysandtheresponsetotuberculinor

TB-specificantigenswillbeneededforscreeningforLTBIinappropriate

patients.

TheTSTisunreliableinpatientswithadvancedCKDandinthoseon

immunosuppressiveagents.Apositivetestmaybeusefulbutanegative

resultcannotbeassumedtobeatruenegative.

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CHEMOPROPHYLAXIS

Therearethreepotentialchemoprophylaxisregimens:

Isoniazid for 6 months (6H),

Rifampicin plus isoniazid for 3 months (3RH)

Rifampicin alone for 4-6 months (4-6R).

Rifampicinandpyrazinamidefor2months(2RZ)wasaregimenusedin

theUSAbutitwasassociatedwithaveryhighrateofhepatitis,witha

numberoffatalitiesreported

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Thechoiceofregimen

6H [ Isoniazid for 6 months] ,whichhasalowerhepatitisrate.

3RHwhichmayhaveadvantagesintermsofshorterdurationandthus

possiblybetteradherenceandalsolessriskofdrugresistancedevelopingif

activediseaseispresent.

4-6R whichalsohasthedisadvantageofasingleagentbutwasbetter

toleratedthan9monthsofisoniazidaloneandcanbeusedfollowingcontact

withisoniazid-resistantdisease.

Nochemoprophylaxisregimeniswhollyeffective;protectiveefficaciesof60-65%havebeenreportedfor6Handof50%for3RH.

Thereisstrongevidencethatregimenslongerthan6Hhaveonlyvery

minimaladditionaladvantageatthecostofanincreaseintheriskof

hepatitis

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ANTITUBERCULOSIS DRUGS IN CHRONIC KIDNEY

DISEASE

Thepharmacologicalpropertiesofantituberculosisdrugsdeterminehowtheirlevelsarelikelytobeinfluencedbyrenalfailure,clearanceduring

dialysisandalsotheirinteractionwithimmunosuppressivedrugsusedin

patientsundergoingrenaltransplantation.

Theexacttimingofadministrationinrelationtodialysisandconcomitant

useofimmunosuppressivedrugsfollowingrenaltransplantation.

Treatmentdurationshould,however,followguidelines,6monthsformost

casesoffullysensitivedisease,withtheexceptionofTBinvolvingtheCNSwhentreatmentshouldbefor1year.

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Isoniazid (H)

Isoniazidismetabolisedbytheliverintolessactivecompoundswhicharethen

excretedbythekidneys.Themostrecentevidenceavailablesuggeststhatisoniazidisdialysableinonlyverysmallamountsandmostclearanceoccurs

fromhepaticmetabolism.

Pharmacokineticstudiesofisoniazidinrenalfailure,however,suggestthat

eventhoughthehalf-lifeofisoniazidisincreasedbyabout45%inslow

acetylators,thisdoesnotleadtosignificantadverseeventsnecessitating

dosagereduction,andtherapeuticdrugmonitoringisnotthoughttobe

necessary.Furthermore,thereisevidencetosuggestthatadministering

isoniazidinreduceddosesmayleadtoreducedpotencyandriskthe

developmentofresistance.

Stage1-3ofCKDIsoniazid300mg

Stage4-5ofCKDIsoniazid300mg

RenalTransplantRecipients15mg/kgmax900mg3X/week

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Side Effects of ISONIAZID

1.Neurotoxicity:grandmalseizures(withnopriorhistory),depressive

psychosis,confusion,nightmares,hallucinations,peripheralneuropathy,

twitchinganddizziness.Encephalopathywasalsoreportedin3of48

dialysispatientswithTB

2.Afewofthosereceivingdialysisalsoexperiencedsignificant

gastrointestinaladverseeffects(jaundice,nauseaandvomiting).

3.Ototoxicityhasbeendescribedovera10-yearperiodinsevenpatientswithCKDreceivingisoniazidtogetherwithotherdrugsbutnot

aminoglycosides.

4.RenalFailure

SiskindMS,ThienemannD,KirlinL.Isoniazid-inducedneurotoxicityinchronicdialysis

patients:reportofthreecasesandareviewoftheliterature.Nephron1993;64:303e6 .

WangHY,ChienCC,ChenYM,etal.Encephalopathycausedbyisoniazidinapatient

withendstagerenaldiseasewithextrapulmonarytuberculosis.RenFail2003;25:135e8.

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Rifampicin (R)

Rifampicinisalsometabolisedbytheliver.Itsinactivemetabolite,

formylrifampicin,isexcretedintheurineanditsmajormetabolite,desacetyl-

rifampicin,isexcretedinbile.

Urinaryexcretionaccountsforverylittleofitseliminationfromthebody,with

onlyabout10%ofagivendosebeingfoundunchangedintheurine.Rifampicin

doesnotappearinsignificantamountsindialysate.

Reportedsideeffectsforrifampicindonotappeartooccurwithsignificantly

increasedfrequencyinpatientswithCKDorondialysis,althoughrifampicinhas

beencitedasararecauseofacuterenalfailure.Assuch,thereiswidespread

agreementthatthedoseofrifampicinneednotbealteredinrenalimpairment

andthatdruglevelsneednotbemonitored

RekhaVV,SanthaT,JawaharMS.Rifampicin-inducedrenaltoxicityduring

retreatmentofpatientswithpulmonarytuberculosis.JAssocPhysiciansIndia

2005;53:811-13

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Pyrazinamide (Z)

Pyrazinamideismetabolisedintheliver.Only3-4%isrenallyexcretedin

unaltered.Althoughthepharmacokineticsofthedrugareunalteredinitiallyin

patientswithrenalfailure,onestudyofitseliminationfoundmuchhigherlevelsdetectableforupto48hafteradministration.Owingtoitseffectonuricacid

retention,thismayleadtohyperuricaemiaandgout.

Pyrazinamideanditsmetabolitesaresignificantlyeliminatedfromthebodyby

haemodialysis,45%appearinginthedialysate.

Nodataareavailableforperitonealdialysis.Duetopossibledelayed

eliminationofthedruganditsmetabolite,thedosageintervalshouldbealtered

instages4and5CKDandinpatientsonhaemodialysis.Therearenocleardataforperitonealdialysis

20 -35 mg/kg per dose three timer per week

EllardGA.Chemotherapyoftuberculosisforpatientswithrenalimpairment.

Nephron1993;64:169e81.(2++)

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Ethambutol (E)

 Around80%ofethambutolisexcretedunchangedbythekidneys.

Inpatientswithrenalfailure,excretionofethambutolwassignificantlyreduced

followingtheusualdoseof15mg/kg.

Itisrenallyexcretedandoculartoxicityislargelydose-dependent.Ethambutol

hasbeendetectedindialysate.

Ithasimprovedefficacywhenadministeredinhighdoseslessoftenthaninadailylowerdose.Serummonitoringshouldbedoneandtroughlevelsshouldbe

lessthan1.0mg/mlat24hpost-dosewithoutdialysis

Recommendation : 15-25 mg/kg per dose three times per week

VarugheseA,BraterDC,BenetLZ,etal.Ethambutolkineticsinpatientswith

impairedrenalfunction.AmRevRespirDis1986;134:34e8.(2+).

CitronK.Ethambutol:areviewwithspecialreferencetooculartoxicity.

Tubercle1969;50(Suppl):32e6.(2++).

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Aminoglycosides

 Around80%ofstreptomycin,kanamycin,amikacinandcapreomycinare

excretedunchangedintheurinewithouthavingundergonesignificant

metabolism.

Streptomycincausessignificantvestibulartoxicitybutlessnephrotoxicity

comparedwiththeotheraminoglycosides.

Thereisanincreaseineliminationtimewithincreasingageanddecliningrenalfunction.Approximately40%ofstreptomycin,amikacin,capreomycinand

kanamycinareremovedbyhaemodialysiswhenthesedrugsaregivenjust

beforehaemodialysis.

TheAmericanThoracicSociety(ATS)recommends12-15

mg/kg/dose2or3times/weekforallofthesedrugs.

Druglevelsshouldbemonitored.

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 Aswithethambutolandpyrazinamide,thedosingintervalshouldbe

increasedratherthanthedosedecreasedasthedrugsexhibitconcentration

dependentbactericidalaction,andlowerdosesmayreducedrugefficacy.Itispreferabletogivestreptomycintwiceorthriceweeklywithoutdecreasingthe

usualdose.

15mg/kg(max1gdaily).Doseisreducedin<50kgand>40yearstomax500to750mgdailyor12-15mg/kg2-3times/week.

Peakplasmaconcentrationsofstreptomycinshouldbebetween15and40

mg/mlandtroughconcentrations<3-5mg/mlor<1mg/mlinCKDorthose

>50years.

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HOW TO CALCULATE CREATININE

CLEARANCE

Cockcroft and Gault equation:

CrCl = [(140 - age) x TBW] / (Scr x 72) (x 0.85 for females)

Where

CrClisCreatinineclearance

TBWisTotalBodyWeight

ScrisSerumCreatininine

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Stage1CKD:Normalcreatinineclearanceandfunctionbuturinary

tractabnormality,forexample,polycystickidney,structuralabnormality.

Stage2CKD:Creatinineclearance60to90ml/min

Stage3CKD:Creatinineclearance30to60ml/min

Stage4CKD:Creatinineclearance15to30ml/min

Stage5CKD:Creatinineclearance<15ml/minwithorwithoutdialysis.

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SECOND-LINE DRUGS USED IN THE MANAGEMENT OF

RESISTANT DISEASE

FLUOROQUINOLONES

•Bothofloxacinandciprofloxacinarealsodependentonrenal

clearanceanddosesshouldbereducedaccordingly.Other

fluoroquinolonesundergosomedegreeofrenalclearancewhichvaries

fromdrugtodrug.

•Levofloxacinundergoesgreaterrenalclearancethanmoxifloxacin.

•FluoroquinolonesdecreasethemetabolismofciclosporinAand

displaceitfromtheboundform,thusincreasingitstoxicity

FishDN,ChowAT.Theclinicalpharmacokineticsof

levofloxacin.ClinPharmacokinet1997;32:101-19.(l+).

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CYCLOSERINE

Upto70%ofcycloserineisexcretedbythekidneyand56%removedby

haemodialysis.

Giventhatdose-relatedneurologicalandpsychiatricsideeffectsofcycloserine

havebeenreportedinupto50%ofpatients,doseadjustmentinthesettingof

renalfailureisrecommended.

TheATSrecommendsincreasingthedoseintervalandsuggests250mgonce

daily

orpreferably500mg3times/week.

Again,itshouldbegivenafterhaemodialysistoavoidunder-dosingand

monitoredforneurotoxicity.

MaloneRS,FishDN,SpiegelDM,etal.Theeffectofhemodialysison

cycloserine,ethionamide,para-aminosalicylate,andclofazimine.

Chest1999;116:984-90.(2+).

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Para-amino salicylic acid (PAS)

 AmodestamountofPAS(6.3%)isclearedbyhaemodialysisbutitsmetabolite,

acetyl-PAS,issubstantiallyremoved.

8-12g/dayintwoorthreedivideddosestwiceshouldbeadequate..

Ethionamide/prothionamide

Ethionamideandprothionamidearenotclearedbythekidneysnorarethey

removedbyhaemodialysis,sonoadjustmenttodosingisneeded.

15to20mg/kg/day(maximum1g;usually500to750mg)insingledailydose

ortwodivideddose

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Clofazimine

Clofazimineisavailableonanamedpatientbasis.ItcanaccumulateinCKD

andcausesskinandhairdiscolouration,photosensitivityandocular

problems.Pharmaceuticaladviceshouldbesought.

Thenormaldoseis100-300mgdailyandthisshouldbereducedtothree

timesweeklyinpatientswithCKDandthoseondialysis.

Linezolid

 Ahigherincidenceofblooddisordersandopticneuropathyhasbeen

reportediflinezolidisusedforlongerthan28days,makingitsuseinthe

managementofTBdifficult.Linezolidisareversiblenon-selectivemonoamineoxidaseinhibitorand

patientsshouldavoideatingtyramine-richfoodssuchascheeseand

productscontainingyeast.Thenormaldoseis600mgevery12h.

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Patients with CKD not on dialysis

Forpatientswithstages4and5CKD,dosingintervalsshouldbeincreasedto

threetimesweeklyforethambutol,pyrazinamideandtheaminoglycosides.

Isoniazid(H),rifampicin(R)andpyrazinamide(Z)canbeusedinnormal

dosesinrenalimpairment.Controlledclinicaltrialshaveshownthatthree

timesweeklytreatmentwithpyrazinamideistherapeuticallymoreeffective

thandailyadministration.

Pyridoxinesupplementationshouldbegivenwithisoniazidtopreventthe

developmentofperipheralneuropathy.

Ethambutolandtheaminoglycosideshavethedisadvantageofrenal

clearance,theneedforincreaseddoseintervalsorreduceddosageand

drugmonitoring.

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HAEMODIALYSIS

Treatmentcanbegivenimmediatelyafterhaemodialysistoavoidpremature

drugremoval.Withthisstrategythereisapossibleriskofraiseddruglevelsof

ethambutolandpyrazinamidebetweendialysissessions.

1.BothrifampicinandisoniazidmaybegivenintheirusualdailyDoses

2.Haemodialysisremovesasignificantamountofpyrazinamideandthe

primarymetaboliteofpyrazinamide,pyrazinoicacid,accumulatesinpatientswithrenalfailure.Advicevariesoverwhetherreductionorspacingofthedose

ofpryazinamideisbestforpatientsonhaemodialysis.Variabledosesof25-30

mg/kgthreetimesweeklyor40mg/kgthreetimesweeklyhavebeen

Recommended.

3.Pyrazinamideshouldbeadministeredimmediatelyafterhaemodialysisor4-6

hbeforehand.

Ethambutolcanbegivenatadoseof15-25mg/kgthreetimesweeklyfor

patientsonregularhaemodialysis.

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PERITONEAL DIALYSIS

Mechanismsfordrugremovaldifferbetweenhaemodialysisandperitoneal

dialysissoitcannotbeassumedthatrecommendationsforhaemodialysisalso

applytoperitonealdialysis.

Onestudyhasshownthatnodoseadjustmentisneededforisoniazid,

rifampicinorpyrazinmideforthetreatmentofsystemicorpulmonaryTBin

patientsonCAPD.

Rifampicinhasahighmolecularweight,lipidsolubilityandproteinbindingcapacityandthesepropertiesmakeitlessdialysablethroughtheperitoneal

membranesothatonlyminimalamountsarerecoveredinthedialysate,

implyingthatoraltherapywithrifampicinmaynotbeadequatefortreatmentof

peritonealTB.Ahnandcolleaguessuggestintraperitonealadministrationof

rifampicinshouldbeconsideredwhentreatingperitonealTB

 AhnC,OhK-H,KimK,etal.Effectofperitonealdialysisonplasmaand

peritonealfluidconcentrationsofisoniazid,pyrazinamideandrifampicin.Perit

DialInt2003;23:362e7  .

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RENAL TRANSPLANTATION

Rifampicininparticularcaninteractwithimmunosuppressiveregimens,

increasingthechanceofgraftrejection,anddosesofmycophenolatemofetil,

tacrolimusandciclosporinmayneedadjustment.Corticosteroiddosesshould

bedoubledinpatientsreceiving

rifampicin.

Rifampicinisthedrugmostlikelytointerferewithimmunosuppressivetreatment

byinductionofanumberofliverenzymesincludinguridinediphosphate-

glucuronosyltransferases,monoamineoxidases,glutathioneS-transferasesandcytochromeP450.

Thedailycorticosteroiddoseshouldbeincreasedtotwicethebaselinedosage

inpatientstakingrifampicin.

Oncerifampicinhasbeenstopped,liverenzymeinductionusuallytakes

2weekstoreturntonormal.

 Azathioprinesometimescauseshepatotoxicity,whichhastobe

differentiatedfromthehepatotoxicityduetoantituberculosisdrugs.

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SUMMARY1. Closecooperationbetweenrenalphysiciansandspecialistsinthe

managementofTBisstronglyrecommended.

2. ActiveTBshouldbeexcludedinpatientswithCKDbyappropriate

investigationsinpatientswhohaveanabnormalchestx-rayorahistoryof

priorpulmonaryorextrapulmonaryTBthathasbeeneitherinadequatelyor

notpreviouslytreated.Chemoprophylaxisshouldbegiven

3. Forpatientswithstages4and5CKD,dosingintervalsshouldbeincreased

tothreetimesweeklyforethambutol,pyrazinamideandthe

aminoglycosides.

4. Treatmentcanbegivenimmediatelyafterhaemodialysistoavoidpremature

drugremoval.

5. Rifampicininparticularcaninteractwithimmunosuppressiveregimens,

increasingthechanceofgraftrejection,anddosesofmycophenolatemofetil,

tacrolimusandciclosporinmayneedadjustment.Corticosteroiddoses

shouldbedoubledinpatientsreceivingrifampicin.

Dosing Recommendaations for adult patients

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DosingRecommendaationsforadultpatientswithreducedrenalfunctionandreceiving

hemodialysis

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