K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Children With Chronic ...

123 Pages·2005·5.19 MB·English

AJKD VOL46,NO4,SUPPL1,OCTOBER2005
CONTENTS
AmericanJournalof
KidneyDiseases
K/DOQI Clinical Practice Guidelines for Bone
Metabolism and Disease in Children
With Chronic Kidney Disease
Tables............................................................................................................................... S1
Figures............................................................................................................................. S1
AcronymsandAbbreviations........................................................................................ S2
Algorithms....................................................................................................................... S3
WorkGroupMembers..................................................................................................... S4
K/DOQIAdvisoryBoardMembers................................................................................. S5
Foreword.......................................................................................................................... S6
Introduction..................................................................................................................... S8
Guideline1.EvaluationofCalciumandPhosphorusMetabolism............................ S12
Guideline2.AssessmentofBoneDiseaseAssociatedwithCKD................................ S18
Guideline3.SurgicalManagementofOsteodystrophy............................................. S23
Guideline4.TargetSerumPhosphorusLevels.......................................................... S26
Guideline5.ManagementofDietaryPhosphorusIntakeinChildrenwithCKD...... S29
Guideline6.UseofPhosphateBindersinCKD......................................................... S32
Guideline7.SerumCalciumandCalcium-PhosphorusProduct.............................. S39
Guideline8.PreventionandTreatmentofVitaminDInsufficiencyandVitaminD
DeficiencyinCKDPatients................................................................................... S48
Guideline9.ActiveVitaminDTherapyinCKDPatients.......................................... S53
Guideline9A.ActiveVitaminDTherapyinPatientswithCKDStages2-4........... S53
Guideline9B.ActiveVitaminDTherapyinPatientsonDialysis(CKDStage5)... S57
Guideline10.DialysateCalciumConcentrations...................................................... S64
Guideline11.RecommendationsfortheUseofGrowthHormoneforChildren
withCKD.............................................................................................................. S68
Guideline12.AluminumOverloadandToxicityinCKD.......................................... S70
Guideline13.TreatmentofAluminumToxicity....................................................... S79
Guideline14.TreatmentofBoneDiseaseinCKD..................................................... S87
Guideline14A.Hyperparathyroid(High-Turnover)BoneDisease....................... S87
Guideline14B.Rickets/Osteomalacia.................................................................... S87
Guideline14C.AdynamicBoneDisease................................................................ S88
Guideline15.ParathyroidectomyinPatientswithCKD........................................... S91
Guideline16.MetabolicAcidosis.............................................................................. S94
Guideline17.BoneDiseaseinthePediatricKidneyTransplantRecipient................ S96
Afterword......................................................................................................................... S99
BiographicalSketchesofWorkGroupMembers........................................................ S101
References....................................................................................................................... S103
Tables
Table1. SignsandSymptomsofBoneDiseaseinChildrenwithCKD..........................................S9
Table2. FrequencyofMeasurementofPTH,Calcium,Phosphorus,TotalCO ,and
2
AlkalinePhosphatasebyStageofCKD...........................................................................S12
Table3. TargetRangeofSerumPTHbyStageofCKD................................................................S12
Table4. HistologicalFeaturesofHigh-TurnoverRenalOsteodystrophy......................................S19
Table5. HistologicalFeaturesofLow-TurnoverRenalOsteodystrophy......................................S19
Table6. RepresentativeNormalValuesforSerumPhosphorus,TotalCalcium,Blood
IonizedCalcium,andAlkalinePhosphataseConcentrations...........................................S26
Table7. DietaryReferenceIntakesofPhosphorusinChildren.....................................................S29
Table8. StepstoCalculatetheInitialBinderPrescription............................................................S33
Table9. Phosphorus-BindingCompounds....................................................................................S33
Table10. RecommendationsforCalciumIntake............................................................................S40
Table11. CalciumContentofCommonCalcium-BasedBinders...................................................S41
Table12. Low-Phosphorus,High-CalciumFoods..........................................................................S42
Table13. PartialListofCalcium-ContainingSupplements............................................................S43
Table14. DeterminingCalciumRequirementsinAdultsAged19-30Years..................................S45
Table15. RecommendedSupplementationforVitaminDDeficiency/Insufficiencyin
PatientswithCKDStages3-4.........................................................................................S48
Table16. SerumLevelsofPTH,Calcium,andPhosphateRequiredforInitiationofOral
VitaminDSterolTherapy,andRecommendedInitialDosesinPatientswith
CKDStages2-4...............................................................................................................S53
Table17. InitialCalcitriolDosingRecommendationsforChildrenonMaintenanceDialysis.......S57
Table18. Aluminum-RelatedDisorders:Features,Causes,andConsiderationsforTherapy........S71
Table19. FrequencyforMeasurementofSerumLevelsofTotalCO ...........................................S94
2
Table20. FrequencyofMeasurementofCalcium,Phosphorus,PTH,andTotalCO after
2
KidneyTransplantation....................................................................................................S96
Figures
Figure1. RelationshipbetweenSerumiPTHLevelsandCCR.........................................................S13
Figure2. SummaryROCAnalysisofErosionsonX-RayasDiagnosticforOsteitisFibrosa..........S14
Figure3. SummaryROCAnalysisofIntactPTHforDiagnosisofHigh-TurnoverBoneDisease...S15
Figure4. SummaryROCAnalysisofIntactPTHforDiagnosisofLow-TurnoverBoneDisease...S16
Figure5. Meta-AnalysisofSizeofEffectonSerumPhosphorusLevelsofCalcium
AcetateversusCalciumCarbonate....................................................................................S35
Figure6. Meta-AnalysisofSizeofHypercalcemicEffectofCalciumCarbonateversus
OtherPhosphateBinders....................................................................................................S35
Figure7. Meta-AnalysisofOralversusIntravenousCalcitriolonPTHSuppression.......................S62
Figure8. IndividualStudyandSummaryEffectsizesfortheEffectofDFOTherapy
onBoneFormationRate....................................................................................................S83
Figure9. IndividualStudyandSummaryEffectSizesfortheEffectofDFOTherapyon
BoneSurfaceAluminumStain...........................................................................................S83
AmericanJournalofKidneyDiseases,Vol46,No4,Suppl1(October),2005:pS1 S1
Acronyms andAbbreviations
1stPTH-IMA First-generationparathyroidhormoneimmunometricassay
2°HPT Secondaryhyperparathyroidism
AIs Adequateintakes
AVN Avascularnecrosis
BCG Bromocresolgreenmethod
BFR Boneformationrate
BMC Bonemineralcontent
BMD Bonemineraldensity
CaR Calcium-sensingreceptors
CAPD Continuousambulatoryperitonealdialysis
CaXP Calcium-phosphorusproduct
CCR Creatinineclearancerate
CKD Chronickidneydisease
CRF Chronicrenalfailure
DBP VitaminD-bindingprotein
DEXA DualenergyX-rayabsorptiometry
DFO Desferrioxamine
DOQI DialysisOutcomesQualityInitiative
DRI DietaryReferenceIntake
EBCT Electronbeamcomputedtomography
EEG Electroencephalogram
ESRD End-stagerenaldisease
GFR Glomerularfiltrationrate
GH,rhGH Growthhormone,recombinanthumangrowthhormone
ICMA Immunochemiluminometricassay
IGF Insulin-likegrowthfactor
IRMA Immunoradiometricassay
K/DOQI KidneyDiseaseOutcomesQualityInitiative
MCV Meancellvolume
MDRD ModificationofDietinRenalDisease
MRI Magneticresonanceimaging
NKF NationalKidneyFoundation
PBM Peakbonemass
PTH Parathyroidhormone
QCT Quantitativecomputedtomography
RDA Recommendeddietaryallowance
RDI Recommendeddailyintake
ROC Receiveroperatingcharacteristics
SCFE Symptomaticproximalfemoralslippedepiphyses
SD Standarddeviation
VDR VitaminDreceptor
VDRE VitaminDreceptorelement,vitaminD-responsiveelement
S2 AmericanJournalofKidneyDiseases,Vol46,No4,Suppl1(October),2005:pS2
Algorithms
Algorithm1. VitaminDSupplementationinCKD(Stages2-4)..................................................................................S49
Algorithm2. ManagementofCKDPatients(Stages2-4)withActiveVitaminDSterols...........................................S54
Algorithm3. ManagingVitaminDSterolsBasedonSerumCalciumLevels..............................................................S59
Algorithm4. ManagingVitaminDSterolsBasedonSerumPhosphorusLevels........................................................S60
Algorithm5. ManagingVitaminDSterolsBasedonPTHLevelsinChildrenNot
ReceivingGrowthHormones.................................................................................................................S61
Algorithm6. EvaluationofAluminumNeurotoxicity..................................................................................................S72
Algorithm7. EvaluationofAluminum-RelatedDisorders:ConsiderationsforDFOTest
andSubsequentDFOTreatment.............................................................................................................S73
Algorithm8. DFOTreatmentAfterP Risebetween50-300(cid:1)g/L............................................................................S80
Al
Algorithm9. SubsequentDFOTreatmentafterP Rise(cid:2)300(cid:1)g/L..........................................................................S81
Al
AmericanJournalofKidneyDiseases,Vol46,No4,Suppl1(October),2005:pS3 S3
K/DOQI Clinical Practice Guidelines for Bone Metabolism and
Disease in Children with Chronic Kidney Disease
Work Group Membership
WorkGroupCo-Chairs
CraigB.Langman,MD IsidroB.Salusky,MD
NorthwesternUniversityFeinbergSchoolofMedicine DavidGeffenSchoolofMedicineatUCLA
Children’sMemorialHospital LosAngeles,CA
Chicago,IL
WorkGroup
LarryGreenbaum,MD,PhD PaulineNelson,RD
MedicalCollegeofWisconsin UCLAMedicalCenter
Milwaukee,WI LosAngeles,CA
HaraldJueppner,MD AnthonyPortale,MD
MassachusettsGeneralHospital UniversityofCaliforniaSanFrancisco
HarvardMedicalSchool SanFrancisco,CA
Boston,MA
BradleyA.Warady,MD
MaryLeonard,MD
TheChildren’sMercyHospital
Children’sHospitalofPhiladelphia
KansasCity,MO
Philadelphia,PA
ConsultantstotheWorkGroup
RichardE.Bowen,MD WilliamL.Oppenheim,MD
AssistantClinicalProfessor DavidGeffenSchoolofMedicineatUCLA
DavidGeffenSchoolofMedicineatUCLA LosAngeles,CA
LosAngeles,CA
K/DOQIAdvisory Board Members
AdeeraLevin,MD,FACP
K/DOQIChair
MichaelRocco,MD,MS
K/DOQIVice-Chair
GarabedEknoyan,MD NathanLevin,MD,FACP
K/DOQICo-ChairEmeritus K/DOQICo-ChairEmeritus
GeorgeBailie,PharmD,PhD WilliamMitch,MD
BryanBecker,MD JosephV.Nally,MD
PeterG.Blake,MD,FRCPC,MBB.Ch GregorioObrador,MD,MPH
AllanCollins,MD,FACP RulanS.Parekh,MD,MS
PeterW.Crooks,MD ThakorG.Patel,MD,MACP
WilliamE.Haley,MD BrianJ.G.Pereira,MD,DM
AlanR.Hull,MD NeilR.Powe,MD
LawrenceHunsicker,MD
ClaudioRonco,MD
BertrandL.Jaber,MD
AntonC.Schoolwerth,MD
CyndaAnnJohnson,MD,MBA
RaymondVanholder,MD,PhD
GeorgeA.Kaysen,MD,PhD
NanetteKassWenger,MD
KarrenKing,MSW,ACSW,LCSW
DavidWheeler,MD,MRCP
MichaelKlag,MD,MPH
WinfredW.Williams,Jr.,MD
CraigB.Langman,MD
Shuin-LinYang,MD
DerrickLatos,MD
DonnaMapes,DNSc,MS Ex-Officio
LindaMcCann,RD,LD,CSR JosephineBriggs,MD
RavindraL.Mehta,MD,FACP
DavidWarnock,MD
MaureenMichael,BSN,MBA
K/DOQI Guideline Development NKF Staff
DonnaFingerhut LoriMormino
MargaretFiorarancio KerryWillis,PhD
AnthonyGucciardo
AJKD VOL46,NO4,SUPPL1,OCTOBER2005
AmericanJournalof
KidneyDiseases
Foreword
T
HE DISCIPLINE OF pediatric nephrol- disease associated with calcium in incorrect
ogy is unique and challenging because it places within the vasculature, similar to that
encompasses the widest developmental stages seen in adult patients who develop CKD de
of life, from in utero presentation of chronic novo. We recognize the pervasive nature of
kidney disease (CKD) through kidney failure CKD,andperhapsamoresubtlemanifestation
presenting in early adulthood. CKD in our of its osteodystrophy, in abnormal neurologi-
patients may arise from embryological distur- caldevelopmentofouryoungestpatients.
bances, genetic mutations, acquired glomeru- Although we were members of the commit-
lopathiesand/ortubulopathies,systemicmeta- tee for the preparation and publication of the
bolic diseases, immune-mediated diseases, or National Kidney Foundation K/DOQI Guide-
thosediseasesthatderive—inpart—fromlife- linesforbonemetabolismanddiseaseinCKD
style choices. The natural history of many of inadults,werecognizedthatthesubjectinthat
these diseases is being rewritten continually, population was filled with enough controversy
as longevity for patients increases beyond that that recommendations for children could not
seen by our mentors before us. We see the properly be placed within it. Therefore, the
influence of socio-demographic distributions leaders of the K/DOQI process acceded to our
on disease expression and severity, and the request for a meeting in Chicago, in October
insufficiencies of organ availability for trans- 2002, to begin the arduous process of sorting
plantationondiseasechronicity. through the literature to produce a pediatric-
In the pediatric population, body calcium specific set of K/DOQI guidelines for bone
balance remains markedly positive to support metabolism and disease in CKD with our col-
both somatic growth and bone mineral accre- leaguesandcommitteemembers.
tion.The sine qua non of pediatric CKD is the The task differed initially from the resultant
marked change in these two processes that
guidelines seen here; but with very limited
leadstothedevastatingclinicaldiseasethatwe
resources, and no external review of extant
term “osteodystrophy.” We have come to real-
literature by a third party, we decided late in
ize that the disorder encompasses marked dis-
2003 to follow the structure of the adult-based
turbancesinmineralhomeostasiswithchronic
bone metabolism and disease guidelines in-
metabolic acidosis, secondary hyperparathy-
stead. We owe great thanks to that group for
roidism (2° HPT), insufficiency of 1,25-dihy-
their wisdom in allowing us to use some of
droxyvitaminD,andfailureoflineargrowthin
theirwork,andadaptitwhereindicatedforthe
addition to extraskeletal disease. Thus, we
aspects unique to pediatric osteodystrophy. It
have seen children, adolescents, and young
became rather clear, quickly, that the area of
adults with an as yet undefined cardiovascular
osteodystrophy in pediatric CKD is highly
uninvestigated, and is a wonderful career-
buildingopportunityforthegenerationofpedi-
©2005bytheNationalKidneyFoundation,Inc.
atric nephrologists who will follow the mem-
0272-6386/05/4604-0101$30.00/0
doi:10.1053/j.ajkd.2005.07.024 bersofthiswritingcommittee.
S6 AmericanJournalofKidneyDiseases,Vol46,No4,Suppl1(October),2005:ppS6-S7
FOREWORD S7
AsCo-Chairs,weoweadeepgratitudetoour and Adeera Levin are to be commended for
committee members. Each worked long hours, their spiritual input to our project (and our-
acceded to our many requests on short notice selves)duringitslongcourse.
with a ‘can-do’attitude, and worked in a colle- As you, the Reader, use these guidelines, you
gial manner that allowed the project to succeed willbequicktoseeitsflawsandweaknesses,asall
inaloftymanner. such guidelines possess. We welcome your input
With the successful completion of our task, directlythroughtheNationalKidneyFoundationto
thoseareasthatneedimprovement,emendation,or
we need to thank many of our colleagues who
removal in subsequent iterations of the work. De-
didnotserveonthecommittee,butwhotaught
spitethiscaveat,webelievethatregularattentionto
us much from their science, and from their
our patients’ osteodystrophy in a manner pro-
empathetic care of patients. We hope we ac-
scribed within the guidelines will lead to an im-
knowledged, by attribution within our text,
provedoutcomeineveryfacetofthedisease.
their work and toil, and we take responsibility
foranymistakesofomissioninthisregard.We
thank the entire staff of the National Kidney
Foundation for their excellent support, and CraigB.Langman,MD
especially that of Mr.Anthony Gucciardo and WorkGroupCo-Chair
Ms. Donna Fingerhut, who were tireless in IsidroB.Salusky,MD
their pursuit of our goals. Drs. Gary Eknoyan WorkGroupCo-Chair
Introduction
GROWTH AND DEVELOPMENT andelaborationofmatrixresultinlineargrowth.
OF THE SKELETON Ossificationproceedstowardtheendofthebone
During childhood and adolescence, total and ultimately forms the growth plate (epiphy-
skeletalcalciumincreasesfromapproxi- seal plate or physis) that is the predominant site
mately25gatbirthto900gand1,200ginadult of longitudinal bone growth. With continued
females and males, respectively. Attainment of maturation,thegrowthplatethinsandeventually
optimal peak bone mass by young adulthood is disappears with fusion of the epiphyseal and
thoughttobethebestprotectionagainstosteopo- diaphysealossificationcenters.Epiphysealunion
rosis later in life.1 Therefore, childhood and occurs at an earlier age in females than males.
adolescence are particularly critical periods for Knowledgeabouttheappearanceofvariousossi-
theestablishmentoflife-longbonehealth.While fication centers in the carpal bones is used to
peakbonemassisstronglyinfluencedbygenetic determine a child’s maturational age, or “bone
factors, full genetic potential is attained only if age.”
nutrition, growth, physical activity, and meta-
bolicandendocrinefunctionareoptimalinchil- BONE MODELING
dren.The clinical features of renal bone disease
Theshapeandstructureofbonesarecontinu-
unique to childhood relate to distinctions be-
ously modified and renovated by two different
tweenthegrowingandthefully-grownskeleton.
processesduringgrowth:modelingandremodel-
The metabolic process of skeletal modeling
ing. Both processes result in the replacement of
throughout growth dictates that pediatric-spe-
old bone tissue with new bone. The remodeling
cific recommendations for the management of
cycle of bone resorption and formation takes
thebonediseaseofCKDbedeveloped.
place throughout life and is vital for microdam-
age repair and maintenance of skeletal integrity.
Incontrast,modelingpredominatesduringgrowth
BONE FORMATION
andpromotesformationofnewboneatlocations
Formation of the skeleton occurs by two pro-
different from the sites of bone resorption. This
cessesofossification—intramembranousanden-
results in increased bone mass and modification
dochondral. Intramembranous ossification is the
ofboneshape.Forexample,increasesincortical
direct mineralization of vascular connective tis-
bonediameterofthediaphysisareduetoconcur-
sue membrane in the plate-like bones of the
rent bone formation on the periosteal (outer)
skull, facial bones, mandible, and clavicle. The
surface and bone resorption on the endosteal
transformationofmesenchymalcellsintoosteo-
(inner)surface.Incontrast,asthebonegrowsin
blasts and production of osteoid matrix convert
length,thewidemetaphysealregionisconverted
theprimitivemesenchymeintobone.Incontrast,
to a narrow diaphysis through resorption of the
bones that involve joints and bear weight form
periosteal surface and bone formation on the
byendochondralossification.Endochondralbone
endosteal surface. Finally, long bones drift in a
formationistheresultofossificationofaninter-
lateral direction during growth due to relatively
mediate cartilage model that is derived from
greater resorption along the medial edge of the
mesenchyme and represents the position and
boneandformationalongthelateraledge.
shape of the bone to be formed at that site.This
In conclusion, bone growth during childhood
providesamechanismfortheformationofbone
andadolescenceinvolvesthecomplexcoordina-
duringgrowth.Inthelongbonesoftheextremi-
tion of varied cell activities on specific bone
ties, the primary center of ossification is located
surfaces.Cartilageproliferation,bonemodeling,
in the central portion of the cartilage model.
andepiphysealclosureareunderthedirectinflu-
Proliferation and hypertrophy of chondrocytes
ence of a variety of hormones and growth fac-
tors, such as growth hormone (GH), thyroid
hormone,estrogen,testosterone,parathyroidhor-
©2005bytheNationalKidneyFoundation,Inc.
mone(PTH),vitaminD,andinsulin-likegrowth
0272-6386/05/4604-0102$30.00/0
doi:10.1053/j.ajkd.2005.07.025 factors (IGF).2 Each of these factors may be
S8 AmericanJournalofKidneyDiseases,Vol46,No4,Suppl1(October),2005:ppS8-S11