KDIGO Clinical Practice Guideline Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease - Mineral and one

Disorder !CKD-M D"

Kidney Disease: Improving Global Outcomes

#n inde$endently incor$orated non$rofit foundation, governed %y an international %oard &ith the stated mission to' (Im$rove the care and outcomes of )idney disease $atients &orld&ide through $romoting coordination, colla%oration, and integration of initiatives to develo$ and im$lement clinical $ractice guidelines*+

KDIGO CKD-M D Guideline ,or) Grou$ Mem%ers

Sharon M. Moe, MD, FASN, FAHA, FACP (Co-chair) United States Geoffrey A. B oc!, MD United States "or#e B. Cannata-And$a, MD, PhD S%ain Graha&e ". ' der, MB, BS, PhD, F(ACP A)stra ia Masaf)&i F)!a#a*a, MD, PhD, FASN "a%an +anda "or#etti, MD, PhD Bra,i Mar!)s -ette er, MD Ger&any Crai# B. .an#&an, MD United States Adeera .e/in, MD, F(CPC Canada

0i &an B. Dr1e!e, MD, F(CP (Co-chair) France A ison M. Mac.eod, MBChB, MD, F(CP United -in#do& .inda McCann, (D, CS(, .D United States Peter A. McC) o)#h, MD, MPH, FACC, FACP, FCCP, FAHA United States S)san M. 2tt, MD United States An#e a 3ee-Moon 4an#, MD, PhD, F(CP Hon# -on# "os5 (. 4eisin#er, MD, FACP +ene,)e a 6 United States Da/id C. 4hee er, MD, F(CP United -in#do&

CKD-M D Guideline Evidence -evie& Team

0)fts Medica Center '(0

:nternationa Methods Cons) tant

-atrin Uh i#, MD, MS Pro7ect Director8 Director, G)ide ine De/e o%&ent (an7ani Moorthi, MD, MPH, MS Assistant Pro7ect Director A&y 'ar ey, BS Pro7ect Coordinator (e9ecca Persson, BA (esearch Assistant

A ison M. Mac.eod, MBChB, MD, F(CP United -in#do&

Guideline Outline
Cha%ter ;< :ntrod)ction and Definition of C-D-MBD and the De/e o%&ent of the G)ide ine State&ents Cha%ter =< Methodo o#ica A%%roach Cha%ter >.;< Dia#nosis of C-D-MBD< Bioche&ica A9nor&a ities Cha%ter >.=< Dia#nosis of C-D-MBD< Bone Cha%ter >.>< Dia#nosis of C-D-MBD< +asc) ar Ca cification

Guideline Outline
Cha%ter ?.;< 0reat&ent of C-D-MBD 0ar#eted at .o*erin# Hi#h Ser)& Phos%hor)s and Maintainin# Ser)& Ca ci)& Cha%ter ?.=< 0reat&ent of A9nor&a P0H .e/e s in C-D-MBD Cha%ter ?.>< 0reat&ent of Bone *ith Bis%hos%honates, other 2steo%orosis Medications, and Gro*th Hor&one Cha%ter @< '/a )ation and 0reat&ent of -idney 0rans% ant Bone Disease Cha%ter A< S)&&ary and (esearch

Cha$ter .
:ntrod)ction and Definition of C-D-MBD and the De/e o%&ent of the G)ide ine State&ents

Definition of CKD-Mineral and one Disorder

A syste&ic disorder of &inera and 9one &eta9o is& d)e to C-D &anifested 9y either one or a co&9ination of the fo o*in#<
#%normalities of calcium, $hos$horus, PT/, or vitamin D meta%olism #%normalities in %one turnover, minerali0ation, volume, linear gro&th, or strength 1ascular or other soft tissue calcification
Moe S, et al. Kidney Int 23' .345, 6772

Definition of -enal Osteodystro$hy

(ena osteodystro%hy is an a teration of 9one &or%ho o#y in %atients *ith C-D. :t is one &eas)re of the s!e eta co&%onent of the syste&ic disorder of C-D-MBD that is B)antifia9 e 9y histo&or%ho&etry of 9one 9io%sy.
Moe S, et al. Kidney Int 23' .345, 6772

Classification of -enal Osteodystro$hy

Turnover High Normal Low

Minerali0ation Normal Abnormal

1olume High Normal Low

Kindly provided by Dr. Susan M. O

Slide courtesy of Susan Ott

Moe! SM e al. A"KD# $%&'! '(()

8e9uential Process for Guideline Develo$ment :irst 8te$s' &# Develop *ues ions and de+ine ou ,omes Pre$aratory 8te$s' '# "ondu, sys ema i, review $# -repare eviden,e pro+ile +or impor an ou ,omes Grading' .# /rade *uali y o+ eviden,e +or ea,h ou ,ome 0# 1an2 rela ive impor an,e o+ ea,h ou ,ome 3# /rade overall *uali y o+ eviden,e a,ross all ou ,omes )# Assess balan,e o+ bene+i s and harms 4# Assess balan,e o+ ne bene+i and ,os s 5# 6ormula e re,ommenda ion and grade s reng h 8u%se9uent 8te$s' &(# 7mplemen and evalua e
/1AD8 9M: '((0

E;tensive Guideline -evie& Process

-D:G2 'Cec)ti/e Co&&ittee and Board (e%resentati/es of Fi/e :nternationa G)ide ine De/e o%&ent Gro)%s 2r#ani,ationa , Sta!eho der, and P)9 ic (e/ie* A co&&ents s)9&itted at each %hase of the re/ie* %rocess are caref) y re/ie*ed and considered 9y the 4or! Gro)% %rior to %)9 ication of the fina #)ide ine

Cha$ter 6

Methodo o#ica A%%roach

Evidence Model for CKD-M D

"KD

Abnormal levels and bioa, ivi y o+ labora ory parame ers#

<a%oratory 8urrogate Outcomes

-@H High Normal Low

"al,ium High Normal Low

-hosphorus High Normal Low

'0COHDD Normal Low

&!'0COHD'D Normal Low

one and C1D 8urrogate Outcomes

9one urnover# os eo,al,in! 9one spe,i+i, al2aline phospha ase! "% erminal ,ross lin2s 9one minerali<a ion >densi y# D?A! *"@ ! *AS 9one urnover! minerali<a ion B s ru, ure# his ology

9one disease# abnormal s ru, ure or +un, ion

=essel and valve disease# abnormal s ru, ure or +un, ion

=essel s i++ness# pulse wave velo,i y! pulse pressure =essel > valve ,al,i+i,a ion# ? %ray! AS! "@! 89"@! MS"@! 7M@ =essel pa en,y# ,oronary angiogram! Doppler dupleE AS

6ra, ures! pain! de,reases in mobili y! s reng h or grow h

"ardiovas,ular disease even s

Clinical Outcomes

Disabili y! de,reased ;OL! hospi ali<a ions! dea h

Inter$reting a surrogate outcome trial

Surroga e Ou ,ome "lini,al ou ,ome rial Observa ional in same drug ,lass @rial C-hospha e 9inder AD Asso,ia ion C-hospha e 9inder 9D "lini,al ou ,ome rial % di++eren drug ,lass C-hospha e 9inder "D

Intervention
Treatment with Phos Binder A

Intervention
Treatment with Phos Binder B

Intervention
Treatment with Phos Binder C

8urrogate Outcome
Slowing of Calcification

8urrogate Outcome
Less Calcification

8urrogate Outcome
Slowing of Calcification

8urrogate Outcome
Slowing of Calcification

Clinical Outcome
Less CVD is!

Clinical Outcome
Less CVD Events

Clinical Outcome
Less CVD Events

7llus ra ion o+ prin,iples ou lined in AsersF /uide +or a Surroga e 8nd -oin @rial 9u,her et al. :AMA &555! '4' C4D# ))&%))4

Step 1: Starting grade for quality of evidence based on study design

G-#DE system for grading 9uality of evidence for an outcome

Step 2: Reduce grade Study quality -1 level if serious limitations -2 levels if very serious limitations Consistency -1 level if important inconsistency Directness -1 level if some uncertainty -2 levels if ma or uncertainty Other: -1 level if sparse or imprecise data -1 level if high probability of reporting bias Step 3: Raise grade Strength of association !1 level is strong"a no plausible confounders" consistent and direct evidence !2 levels if very strong"b no ma or threats to validity and direct evidence Other !1 level if evidence of a dose response gradient !1 level if all residual plausible confounders would have reduced the observed effect

High for randomized trial Moderate for quasirandomized trial Low for observational study

Final grade for quality of evidence for an outcomec High Moderate Low Very low

Very Low for any other evidence

:inal grade for overall 9uality of evidence

Quality of Grade Evidence ! High eaning #e are confident that the true effect lies close to that of the estimate of the effect$

"

Moderate %he true effect is li&ely to be close to the estimate of the effect" but there is a possibility that it is substantially different$ Low Very low %he true effect may be substantially different from the estimate of the effect$ %he estimate of effect is very uncertain" and often will be far from the truth$
Guyatt G/, et al. M= >>2' .743, 677?

# $

@omenclature and Descri$tion for -ating Guideline -ecommendations

Grade %mplications &atients #linicians &olicy

'evel 1 '#e recommend(

Most people in your situation would want the recommended course of action and only a small proportion would not$

Most patients should receive the recommended course of action$

%he recommendation can be adopted as a policy in most situations$

'evel 2 '#e suggest(

%he ma ority of people in )ifferent choices will %he recommendation is your situation would be appropriate for li&ely to require debate want the recommended different patients$ *ach and involvement of course of action" but patient needs help to sta&eholders before many would not$ arrive at a policy can be management decision determined$ consistent with her or his values and preferences$

Determinants of the strength of a recommendation

Factor "alance bet(een desirable and undesirable effects #omment )*e larger t*e difference bet(een t*e desirable and undesirable effects+ t*e more li,ely a strong recommendation (arranted- )*e narro(er t*e gradient+ t*e more li,ely a (ea, recommendation (arranted-

Quality of t*e evidence .alues and preferences

)*e *ig*er t*e quality of evidence+ t*e more li,ely a strong recommendation (arranted)*e more variability in values and preferences+ or t*e more uncertainty in values and preferences+ t*e more li,ely a (ea, recommendation (arranted-

#osts /resource allocation0

)*e *ig*er t*e costs of an intervention1t*at is+ t*e more resources consumed1t*e less li,ely a strong recommendation (arrantedGuyatt G/, et al. M= >>2' .743, 677?

:inal KDIGO Grading of -ecommendations

Grade for Strengt* of Recommendation 'evel 1 Grade for Quality of Evidence ! " # $

Strengt* +trong

2ording '#e recommend, should( '#e suggest, might(

Quality of Evidence High Moderate Low Very low

'evel 2

#ea&

/rading Op ions# &A! &9! &"! &D! 'A! '9! '"! 'D! or Gno gradedH

Cha$ter >*.

Dia#nosis of C-D-MBD< Bioche&ica A9nor&a ities

-is) of all-cause mortality associated &ith com%inations of %aseline serum $hos$horus and calcium categories %y PT/ level !from DOPP8"

Tentori :, et al. #=KD 56' 5.3, 677?

Diagnosis of CKD-MBD: Biochemical Abnormalities

>.;.;. 4e reco&&end &onitorin# ser)& e/e s of ca ci)&, %hos%hor)s, P0H, and a !a ine %hos%hatase acti/ity 9e#innin# in C-D Sta#e > (;C). :n chi dren, *e s)##est s)ch &onitorin# 9e#innin# in C-D Sta#e = (=D). >.;.=. :n %atients *ith C-D Sta#es >-@D, it is reasona9 e to 9ase the freB)ency of &onitorin# ser)& ca ci)&, %hos%hor)s, and P0H on the %resence and &a#nit)de of a9nor&a ities, and the rate of %ro#ression of C-D (not #raded).

Diagnosis of CKD-MBD: Biochemical Abnormalities

>.;.=< (easona9 e &onitorin# inter/a s *o) d 9e<

D :n C-D sta#e >< for ser)& ca ci)& and

%hos%hor)s, e/ery A-;= &onths8 and for P0H, 9ased on 9ase ine e/e and C-D %ro#ression.

D :n C-D sta#e ?< for ser)& ca ci)& and %hos%hor)s, e/ery >-A &onths8 and for P0H, e/ery A-;= &onths. D :n C-D sta#es @, inc )din# @D< for ser)& ca ci)& and %hos%hor)s, e/ery ;-> &onths8 and for P0H, e/ery >-A &onths.

Diagnosis of CKD-MBD: Biochemical Abnormalities

>.;.=< (easona9 e &onitorin# inter/a s *o) d 9e<
D :n C-D sta#es ?-@D< for a !a ine %hos%hatase acti/ity, e/ery ;= &onths, or &ore freB)ent y in the %resence of e e/ated P0H (see Cha%ter >.=). :n C-D %atients recei/in# treat&ents for C-DMBD, or in *ho& 9ioche&ica a9nor&a ities are identified, it is reasona9 e to increase the freB)ency of &eas)re&ents to &onitor for trends and treat&ent efficacy and side-effects (not #raded).

Diagnosis of CKD-MBD: Biochemical Abnormalities

>.;.>. :n %atients *ith C-D sta#es >E@D, *e s)##est that =@(2H)D (ca cidio ) e/e s &i#ht 9e &eas)red, and re%eated testin# deter&ined 9y 9ase ine /a )es and thera%e)tic inter/entions (=C). 4e s)##est that /ita&in D deficiency and ins)fficiency 9e corrected )sin# treat&ent strate#ies reco&&ended for the #enera %o%) ation (=C). >.;.?. :n %atients *ith C-D sta#es >E@D, *e reco&&end that thera%e)tic decisions 9e 9ased on trends rather than on a sin# e a9oratory /a )e, ta!in# into acco)nt a a/ai a9 e C-DEMBD

assess&ents

(;C).

Diagnosis of CKD-MBD: Biochemical Abnormalities

>.;.@. :n %atients *ith C-D sta#es >E@D, *e s)##est that indi/id)a /a )es of ser)& ca ci)& and %hos%hor)s, e/a )ated to#ether, 9e )sed to #)ide c inica %ractice rather than the &athe&atica constr)ct of ca ci)&%hos%hor)s %rod)ct (Ca F P) (=D). >.;.A. :n re%orts of a9oratory tests for %atients *ith C-D sta#es >E@D, *e reco&&end that c inica a9oratories infor& c inicians of the act)a assay &ethod in )se and re%ort any chan#e in &ethods, sa&% e so)rce (% as&a or ser)&), and hand in# s%ecifications to faci itate the a%%ro%riate inter%retation of 9ioche&istry data (;B).

Cha$ter >*6

Dia#nosis of C-D-MBD< Bone

Prevalance of ty$es of %one disease as determined %y %one %io$sy in $atients &ith CKD-M D

#D, adynamic %oneA O:, osteitis fi%rosaA OM, osteomalacia.

Diagnosis of CKD-MBD: Bone

>.=.;. :n %atients *ith C-D sta#es >E@D, it is reasona9 e to %erfor& a 9one 9io%sy in /ario)s settin#s inc )din#, 9)t not i&ited to< )neC% ained fract)res, %ersistent 9one %ain, )neC% ained hy%erca ce&ia, )neC% ained hy%o%hos%hate&ia, %ossi9 e a )&in)& toCicity, and %rior to thera%y *ith 9is%hos%honates in %atients *ith C-DEMBD (not #raded). >.=.=. :n %atients *ith C-D sta#es >E@D *ith e/idence of C-DEMBD, *e s)##est that BMD testin# not 9e %erfor&ed ro)tine y, 9eca)se BMD does not %redict fract)re ris! as it does in the #enera %o%) ation, and BMD does not %redict the ty%e of rena osteodystro%hy (=B).

Diagnosis of CKD-MBD: Bone

>.=.>. :n %atients *ith C-D sta#es >E@D, *e s)##est that &eas)re&ents of ser)& P0H or 9one-s%ecific a !a ine %hos%hatase can 9e )sed to e/a )ate 9one disease 9eca)se &ar!ed y hi#h or o* /a )es %redict )nder yin# 9one t)rno/er (=B). >.=.?. :n %atients *ith C-D sta#es >E@D, *e s)##est not to ro)tine y &eas)re 9one-deri/ed t)rno/er &ar!ers of co a#en synthesis (s)ch as %roco a#en ty%e : C-ter&ina %ro%e%tide) and 9rea!do*n (s)ch as ty%e : co a#en cross- in!ed te o%e%tide, cross- a%s, %yridino ine, or deoCy%yridino ine) (=C).

Diagnosis of CKD-MBD: Bone

>.=.@. 4e reco&&end that infants *ith C-D sta#es =E@D sho) d ha/e their en#th &eas)red at east B)arter y, *hi e chi dren *ith C-D sta#es =E@D sho) d 9e assessed for inear #ro*th at east ann)a y (;B).

Cha$ter >*>

Dia#nosis of C-D-MBD< +asc) ar Ca cification

Diagnosis of CKD-MBD: Vascular Calcification

>.>.;. :n %atients *ith C-D sta#es >E@D, *e s)##est that a atera a9do&ina radio#ra%h can 9e )sed to detect the %resence or a9sence of /asc) ar ca cification, and an echocardio#ra& can 9e )sed to detect the %resence or a9sence of /a /) ar ca cification, as reasona9 e a ternati/es to co&%)ted to&o#ra%hy-9ased i&a#in# (=C). >.>.=. 4e s)##est that %atients *ith C-D sta#es >E @D *ith !no*n /asc) arG/a /) ar ca cification 9e considered at hi#hest cardio/asc) ar ris! (=A). :t is reasona9 e to )se this infor&ation to #)ide the &ana#e&ent of C-DEMBD (not #raded).

Cha$ter 4*.
0reat&ent of C-D-MBD 0ar#eted at .o*erin# Hi#h Ser)& Phos%hor)s and Maintainin# Ser)& Ca ci)&

Treatment of CKD-MBD: Phos horus an! Calcium

?.;.;. :n %atients *ith C-D sta#es >E@, *e s)##est &aintainin# ser)& %hos%hor)s in the nor&a ran#e (=C). :n %atients *ith C-D sta#e @D, *e s)##est o*erin# e e/ated %hos%hor)s e/e s to*ard the nor&a ran#e (=C). ?.;.=. :n %atients *ith C-D sta#es >E@D, *e s)##est &aintainin# ser)& ca ci)& in the nor&a ran#e (=D).

Treatment of CKD-MBD: Phos horus an! Calcium

?.;.>. :n %atients *ith C-D sta#e @D, *e s)##est )sin# a dia ysate ca ci)& concentration 9et*een ;.=@ and ;.@H &&o G (=.@ and >.H &'BG ) (=D). ?.;.?. :n %atients *ith C-D sta#es >E@ (=D) and @D (=B), *e s)##est )sin# %hos%hate-9indin# a#ents in the treat&ent of hy%er%hos%hate&ia. :t is reasona9 e that the choice of %hos%hate 9inder ta!es into acco)nt C-D sta#e, %resence of other co&%onents of C-DEMBD, conco&itant thera%ies, and side-effect %rofi e (not #raded).

Treatment of CKD-MBD: Phos horus an! Calcium

?.;.@. :n %atients *ith C-D sta#es >E@D and hy%er%hos%hate&ia, *e reco&&end restrictin# the dose of ca ci)&-9ased %hos%hate 9inders andGor the dose of ca citrio or /ita&in D ana o# in the %resence of %ersistent or rec)rrent hy%erca ce&ia (;B). :n %atients *ith C-D sta#es >E@D and hy%er%hos%hate&ia, *e s)##est restrictin# the dose of ca ci)& 9ased %hos%hate 9inders in the %resence of arteria ca cification (=C) andGor adyna&ic 9one disease (=C) andGor if ser)& P0H e/e s are %ersistent y o* (=C).

Treatment of CKD-MBD: Phos horus an! Calcium

?.;.A. :n %atients *ith C-D sta#es >E@D, *e reco&&end a/oidin# the on#-ter& )se of a )&in)&containin# %hos%hate 9inders and, in %atients *ith C-D sta#e @D, a/oidin# dia ysate a )&in)& conta&ination to %re/ent a )&in)& intoCication (;C). ?.;.I. :n %atients *ith C-D sta#es >E@D, *e s)##est i&itin# dietary %hos%hate inta!e in the treat&ent of hy%er%hos%hate&ia a one or in co&9ination *ith other treat&ents (=D). ?.;.J. :n %atients *ith C-D sta#e @D, *e s)##est increasin# dia ytic %hos%hate re&o/a in the treat&ent

of %ersistent hy%er%hos%hate&ia (=C).

Cha$ter 4*6
0reat&ent of A9nor&a P0H .e/e s in C-D-MBD

Com$arison of PT/ levels to underlying %one histology in chronic hemodialysis $atients

arreto :C, et al* Kidney Int B>'BB., 677?

Treatment of CKD-MBD: Abnormal PT" #e$els

?.=.;. :n %atients *ith C-D sta#es >E@ not on dia ysis, the o%ti&a P0H e/e is not !no*n. Ho*e/er, *e s)##est that %atients *ith e/e s of intact P0H (iP0H) a9o/e the )%%er nor&a i&it of the assay are first e/a )ated for hy%er%hos%hate&ia, hy%oca ce&ia, and /ita&in D deficiency (=C).

:t is reasona9 e to correct these a9nor&a ities *ith any or a of the fo o*in#< red)cin# dietary %hos%hate inta!e and ad&inisterin# %hos%hate 9inders, ca ci)& s)%% e&ents, andGor nati/e /ita&in D (not #raded).

Treatment of CKD-MBD: Abnormal PT" #e$els

?.=.=. :n %atients *ith C-D sta#es >E@ not on dia ysis, in *ho& ser)& P0H is %ro#ressi/e y risin# and re&ains %ersistent y a9o/e the )%%er i&it of nor&a for the assay des%ite correction of &odifia9 e factors, *e s)##est treat&ent *ith ca citrio or /ita&in D ana o#s (=C).

Treatment of CKD-MBD: Abnormal PT" #e$els

?.=.>. :n %atients *ith C-D sta#e @D, *e s)##est &aintainin# iP0H e/e s in the ran#e of a%%roCi&ate y t*o to nine ti&es the )%%er nor&a i&it for the assay (=C).

4e s)##est that &ar!ed chan#es in P0H e/e s in either direction *ithin this ran#e %ro&%t an initiation or chan#e in thera%y to a/oid %ro#ression to e/e s o)tside of this ran#e (=C).

Treatment of CKD-MBD: Abnormal PT" #e$els

?.=.?. :n %atients *ith C-D sta#e @D and e e/ated or risin# P0H, *e s)##est ca citrio , or /ita&in D ana o#s, or ca ci&i&etics, or a co&9ination of ca ci&i&etics and ca citrio or /ita&in D ana o#s 9e )sed to o*er P0H (=B). It is reasona%le that the initial drug selection for the treatment of elevated PT/ %e %ased on serum calcium and $hos$horus levels and other as$ects of CKDCM D %not gra!e!&* It is reasona%le that calcium or non-calcium-%ased $hos$hate %inder dosage %e adDusted so that treatments to control PT/ do not com$romise levels of $hos$horus and calcium %not gra!e!&*

Treatment of CKD-MBD: Abnormal PT" #e$els

?.=.?. (Contin)ed)
,e recommend that, in $atients &ith hy$ercalcemia, calcitriol or another vitamin D sterol %e reduced or sto$$ed %'B&* ,e suggest that, in $atients &ith hy$er$hos$hatemia, calcitriol or another vitamin D sterol %e reduced or sto$$ed %(D&* ,e suggest that, in $atients &ith hy$ocalcemia, calcimimetics %e reduced or sto$$ed de$ending on severity, concomitant medications, and clinical signs and sym$toms %(D&*

Treatment of CKD-MBD: Abnormal PT" #e$els

?.=.?. (Contin)ed)< ,e suggest that, if the intact PT/ levels fall %elo& t&o times the u$$er limit of normal for the assay, calcitriol, vitamin D analogs, andEor calcimimetics %e reduced or sto$$ed %(C&* ?.=.@. :n %atients *ith C-D sta#es >E@D *ith se/ere hy%er%arathyroidis& (HP0) *ho fai to res%ond to &edica G%har&aco o#ica thera%y, *e s)##est %arathyroidecto&y (=B).

Cha$ter 4*>
0reat&ent of Bone *ith Bis%hos%honates, other 2steo%orosis Medications, and Gro*th Hor&one

Treatment of Bone: )steo orosis Me!ications

?.>.;. :n %atients *ith C-D sta#es ;E= *ith osteo%orosis andGor hi#h ris! of fract)re, as identified 9y 4or d Hea th 2r#ani,ation criteria, *e reco&&end &ana#e&ent as for the #enera %o%) ation (;A). ?.>.=. :n %atients *ith C-D sta#e > *ith P0H in the nor&a ran#e and osteo%orosis andGor hi#h ris! of fract)re, as identified 9y 4or d Hea th 2r#ani,ation criteria, *e s)##est treat&ent as for the #enera %o%) ation (=B).

Treatment of Bone: )steo orosis Me!ications

?.>.>. :n %atients *ith C-D sta#e > *ith 9ioche&ica a9nor&a ities of C-DEMBD and o* BMD andGor fra#i ity fract)res, *e s)##est that treat&ent choices ta!e into acco)nt the &a#nit)de and re/ersi9i ity of the 9ioche&ica a9nor&a ities and the %ro#ression of C-D, *ith consideration of a 9one 9io%sy (=D). ?.>.?. :n %atients *ith C-D sta#es ?E@D ha/in# 9ioche&ica a9nor&a ities of C-DEMBD, and o* BMD andGor fra#i ity fract)res, *e s)##est additiona in/esti#ation *ith 9one 9io%sy %rior to thera%y *ith antiresor%ti/e a#ents (=C).

Treatment of Bone: *ro+th "ormone

?.>.@. :n chi dren and ado escents
*ith C-D sta#es =E@D and re ated hei#ht deficits, *e reco&&end treat&ent *ith reco&9inant h)&an #ro*th hor&one *hen additiona #ro*th is desired, after first addressin# &a n)trition and 9ioche&ica a9nor&a ities of C-DEMBD (;A).

Cha$ter 5
'/a )ation and 0reat&ent of -idney 0rans% ant Bone Disease

Ki!ne, Trans lant Bone Disease

@.;. :n %atients in the i&&ediate %ostE !idney-trans% ant %eriod, *e reco&&end &eas)rin# ser)& ca ci)& and %hos%hor)s at east *ee! y, )nti sta9 e (;B). @.=. :n %atients after the i&&ediate %ostE !idney trans% ant %eriod, it is reasona9 e to 9ase the freB)ency of &onitorin# ser)& ca ci)&, %hos%hor)s, and P0H on the %resence and &a#nit)de of a9nor&a ities, and the rate of %ro#ression of C-D (not #raded).

Ki!ne, Trans lant Bone Disease

@.=. (Contin)ed)<

(easona9 e &onitorin# inter/a s *o) d 9e<

In CKD stages .C>T, for serum calcium and $hos$horus, every 2C.6 monthsA and for PT/, once, &ith su%se9uent intervals de$ending on %aseline level and CKD $rogression* In CKD stage 4T, for serum calcium and $hos$horus, every >C2 monthsA and for PT/, every 2C.6 months*

Ki!ne, Trans lant Bone Disease

@.=. (Contin)ed)<

(easona9 e &onitorin# inter/a s *o) d 9e<

In CKD stage 5T, for serum calcium and $hos$horus, every .C> monthsA and for PT/, every >C2 months* In CKD stages >C5T, measurement of al)aline $hos$hatases annually, or more fre9uently in the $resence of elevated PT/ !see Cha$ter >*6"*

Ki!ne, Trans lant Bone Disease

@.=. (Contin)ed)

:n C-D %atients recei/in# treat&ents for C-DE MBD, or in *ho& 9ioche&ica a9nor&a ities are identified, it is reasona9 e to increase the freB)ency of &eas)re&ents to &onitor for efficacy and side-effects (not #raded). :t is reasona9 e to &ana#e these a9nor&a ities as for %atients *ith C-D sta#es >E@ (not #raded) (see Cha%ters ?.; and ?.=).

Ki!ne, Trans lant Bone Disease

@.> :n %atients *ith C-D sta#es ;E@0, *e s)##est that =@(2H)D (ca cidio ) e/e s &i#ht 9e &eas)red, and re%eated testin# deter&ined 9y 9ase ine /a )es and inter/entions (=C). @.?. :n %atients *ith C-D sta#es ;E@0, *e s)##est that /ita&in D deficiency and ins)fficiency 9e corrected )sin# treat&ent strate#ies reco&&ended for the #enera %o%) ation (=C). @.@. :n %atients *ith an esti&ated # o&er) ar fi tration rate #reater than a%%roCi&ate y >H & G&in %er ;.I>&=, *e s)##est &eas)rin# BMD in the first > &onths after !idney trans% ant if they recei/e corticosteroids, or ha/e ris! factors for osteo%orosis as in the #enera %o%) ation (=D).

Ki!ne, Trans lant Bone Disease

@.A :n %atients in the first ;= &onths after !idney trans% ant *ith an esti&ated # o&er) ar fi tration rate #reater than a%%roCi&ate y >H & G&in %er ;.I>& = and o* BMD, *e s)##est that treat&ent *ith /ita&in D, ca citrio G a faca cido , or 9is%hos%honates 9e considered (=D).
,e suggest that treatment choices %e influenced %y the $resence of CKDCM D, as indicated %y a%normal levels of calcium, $hos$horus, PT/, al)aline $hos$hatases, and 65!O/"D %(C&* It is reasona%le to consider a %one %io$sy to guide treatment, s$ecifically %efore the use of %is$hos$honates due to the high incidence of adynamic %one disease %not gra!e!&*

0here are ins)fficient data to #)ide treat&ent after

the first ;= &onths.

Ki!ne, Trans lant Bone Disease

@.I. :n %atients *ith C-D sta#es ?E@0, *e
s)##est that BMD testin# not 9e %erfor&ed ro)tine y, 9eca)se BMD does not %redict fract)re ris! as it does in the #enera %o%) ation and BMD does not %redict the ty%e of !idney trans% ant 9one disease (=B). !no*n o* BMD, *e s)##est &ana#e&ent as for %atients *ith C-D sta#es ?E@ not on dia ysis, as detai ed in Cha%ters ?.; and ?.= (=C).

@.J. :n %atients *ith C-D sta#es ?E@0 *ith

-esearch -ecommendations
De/e o% a ris!-stratification too 9ased on C-DMBD co&%onents and e/a )ate its %redicti/e acc)racy for c inica o)tco&es in %atients *ith C-D sta#es >-@, @D, and >-@0. Deter&ine if, in %atients *ith C-D-MBD, a sin# e &eas)re&ent of BMD (&eas)red 9y DFA or BC0) and seria chan#es in BMD %redict fract)res. Deter&ine if the %resence or a9sence of /asc) arG/a /) ar ca cification in %atients *ith C-DMBD is an a%%ro%riate stratification and se ection too to identify indi/id)a s *ho &ay 9enefit fro& s%ecific inter/entions.

-esearch -ecommendations
Deter&ine if the effect of an intensi/e C-D-MBD treat&ent a%%roach (e.#., %rotoco -dri/en co&9ination thera%y to achie/e s%ecific ser)& %hos%hor)s and P0H tar#ets) /s. a ess intensi/e treat&ent a%%roach (e.#., %rotoco -dri/en co&9ination thera%y a o*in# hi#her ser)& %hos%hor)s and P0H tar#ets) /s. standard care i&%ro/es c inica o)tco&es in %atients *ith C-D sta#es >@D. Deter&ine if treatin# do*n to nor&a ser)& %hos%hor)s e/e s (as co&%ared to %hos%hor)s e/e s of @.@-A.@ &#Gd.) *ith the )se of co&9inations of different %hos%hate 9inders and other a%%roaches i&%ro/es c inica o)tco&es in %atients *ith C-D sta#es ?-@D and ?-@0.

-esearch -ecommendations
Deter&ine if treat&ent to a o*er /s. a hi#her ser)& P0H tar#et i&%ro/es or *orsens c inica o)tco&es in %atients *ith C-D sta#es >-@, C-D sta#e @D, and C-D sta#es >-@0. Deter&ine if treat&ent *ith /ita&in D (er#oca cifero or cho eca cifero ) or ca cidio K=@(2H)DL, co&%ared to ca citrio or /ita&in D ana o#s, i&%ro/es c inica o)tco&es in %atients *ith C-D sta#es >-@, C-D sta#e @D, and C-D sta#es ;-@0. Deter&ine *hich %hos%hate 9inders and other ser)& %hos%hor)sE o*erin# treat&ents are a9 e to i&%ro/e s)r/i/a in %atients *ith C-D sta#es >-@D and C-D sta#es >-@0.

-esearch -ecommendations
Deter&ine if treat&ent *ith 9is%hos%honates, teri%aratide, or ra oCifene red)ces fract)res or /asc) ar ca cification in %atients *ith C-D sta#es >-@D and C-D sta#es ;-@0. Deter&ine if strate#ies to re/erse adyna&ic 9one disease 9y &eas)res s)ch as endo#eno)s sti&) ation of P0H secretion (e.#., )sin# o*ca ci)& dia ysate) or eCo#eno)s teri%aratide ad&inistration i&%act c inica o)tco&es in %atients *ith C-D sta#es ?-@D or C-D sta#es ;-@0, co&%ared to % ace9o.

M)estions