iron supplement in ckd paents in china - kdigo.org · consensus on iron supplement in ckd paents in...

IronSupplementinCKDPa3entsinChinaChuan-MingHao

FudanUniversityNephrologyIns3tuteDivisionofNephrology,HuashanHospitalFudanUniversity

Contents

•  ConsensusonanemiamanagementinCKDpa0entsinChina

•  AnemiacontrolinCKDpa0entsinChina•  HepcidinandironhomeostasisinCKD

Recommenda3onsforUseofIronSupplementa3oninPa3entswithCKD

Recommenda3onsforUseofIronSupplementa3oninPa3entswithCKD

*Basedonpa0entsymptomsandoverallclinicalgoals,includingavoidanceoftransfusion,improvementinanemia-relatedsymptoms,anda?erexclusionofac0veinfec0on.

***Basedonpa0entsymptomsandoverallclinicalgoalsincludingavoidanceoftransfusionandimprovementinanemia-relatedsymptoms,anda?erexclusionofac0veinfec0onandothercausesofESAhyporesponsiveness.

•  Limita3onincurrentironstatusassessment

•  Longtermsafetyconcernsoni.v.iron

•  …

ConsensusonIronsupplementinCKDPa3entsinChina

•  CriteriaforironsupplementinCKD–  CKDanemicpa0entsnotonESAoriron

•  TSAT<30%;Ferri0n<500ug/L:atrialofIViron(ND-CKD,trial1-3monthsoforaliron,switchtoIVironifnoeffect)

–  CKDanemicpa0entsareonESAbutnotiron•  AnincreaseinHborreduc0onofESAsaredesiredandTSAT<30%;Ferri0n<500ug/L:trialofIViron(ND-CKD,trial1-3monthsoforaliron,switchtoIVironifnoeffect)

–  Ifferri0n>500ug/L,werecommendnoIViron.However,ifincreaseofESAsdoesnotimproveanemiaandacuteinfec0onexcluded,youmaytryIViron.

中华肾脏病杂志2014年9月第30卷第9期中国医师协会肾内科医师分会肾性贫血诊断和治疗共识专家组

ConsensusonIronsupplementinCKDPa0entsinChina

•  Ironsupplementanddosages–  ND-CKDorPD:oralironfirst,orifneededIVIron.–  HD: preferablyIViron–  OralIron:200mg/day,reevaluatein1-3months.Ifnotreachedthegoalornottolerant,switchtoIViron

–  IViron:(1)HDpa0ents,IViron;Ini0a0on:1000mg,ifferri0n≤500ug/L andTSAT≤30%,repeat;(2)Maintenance: 100mg/1-2weeks, dependsonresponse,ironstatus,Hb,ESAetc.

–  IfTSAT ≥50% and/or≥800ug/L,stopivironfor3months.IfTSATandferri0n≤50% and≤800ug/Lrespec0vely,resumeIVironatreduceddoesby1/3-1/2.

中华肾脏病杂志2014年9月第30卷第9期中国医师协会肾内科医师分会肾性贫血诊断和治疗共识专家组

BeijingChaoyangHospital•  maintenancehemodialysis,•  Hbconcentra0on60–90g/l•  ferri0n(SF)<500ng/ml•  TSAT<30%

HanLi&Shi-XiangWangBloodPurif2008;26:151–156

0 4 8 1260

80

100

120

140

i.v. Iron p.o. iron

Weeks

Hb

0 4 8 122000

4000

6000

8000

Weeks

EPO

, IU

/Wee

k

0 4 8 12100

200

300

400

500

Weeks

Ferr

itin

ug/L

0 4 8 1220

25

30

35

40

TSAT %

HanLi&Shi-XiangWangBloodPurif2008;26:151–156

Contents



ChinaDialysisPa3entsHb≥100g/L

2012 2013 2014 2015 mean % mean % mean % mean %

Hb (g/L) 97 47.92% 99 50.25% 101 55.41% 102 57.31%

ChinaDialysisRegistryprovidedbyDr.CaiG

2012 China Maintenance Dialysis Patients TSAT

ChinaDialysisRegistry

2012 China Maintenance Dialysis Patients Serum Ferritin

ChinaDialysisRegistry

AnemiaManagementintheChinaDialysisOutcomesandPrac3cePaNernsStudy(DOPPS）

(Beijing,ShanghaiandGuangzhou)

ZuoetalBloodPurif2016;42:33–43

CausesofESRDAnemiaManagementintheChinaDOPPS


HbandIronStatus(AnemiaManagementintheChinaDOPPS)


Distribu3onofFacilityPercentageofPa3entswithHgb<9g/dlbyRegion


IronandESAUse(AnemiaManagementintheChinaDOPPS)


< 100100 ~ 110110 ~ 120120 ~ 130> 130

Hb (g/L)8.25%

17.53%

34.02%

30.93%

9.28%

腹膜透析患者血红蛋白水平

AnemiaControlinPDPa3entsinHuashanHospital

97Pa0entsfromShanghaicityDataof2015.6–2016.6

Unpublisheddata

AnemiaControlinPDPa3entsinHuashanHospital

Hb (g/L) < 100 100 ~110 110 ~ 120 120 ~ 130 >130

Ferritin (ng/mL) 188 (154,454) 250 (170,298) 239 (157,347) 211 (107,305) 143 (129,184)

TSAT (%) 25.0 ± 4.1 28.7 ± 8.1 30.8 ±7.3 31.2 ± 7.6 33.7 ± 8.0

EPO (1000xU/mo) 40.0 (32.5,55) 30.0 (30,40) 25 (20,35) 20 (15,20) 10 (10,20)

Iv iron (mg/year) 400 (125,1275) 200 (0,750) 200 (0,400) 0 (0,225) 0 (0,300)

IvIronuse:47.4%Oraliron:2.1%EPO:97% ZhuTetalUnpublisheddata

HeterogeneityinAnemiaManagementinCKDPa3entinChina

•  Insurancecoverageorreimbursementcap•  Prac0cepapernofphysician(two-0mesweeklyhemodialysisismorecommonlyprac0cedinChina)

•  DifferentESAs


AnemiainPa3entswithNon-dialysisChronicKidneyDiseaseinShanghaiArea

LietalMedicine(2016)95:24(e3872)

UnderlyingDiseasesofCKD


AnemiainPre-dialysisCKD

ModifiedfromLietalMedicine(2016)95:24(e3872)

AnemiadefinedasaHbof13.0g/dLinmenand12.0g/dLinwomen

CKD1 CKD2 CKD3 CKD4 CKD50

20

40

60

80

100 DNHTGN

%

IronStatusinPa0entswithNon-dialysisChronicKidneyDiseaseinShanghaiArea


Contents



ThekidneyisthephysiologicsourceofEPOintheadult

FarsijanietalJClinInvest.doi:10.11722016

IronAbsorp3onandStorage

Fe3+ Fe2+ Fe2+ DMT1 FPN Fe3+ FPN

HIF

DcytB

铁调素 Hepcidin

Erythropoesis

Intestine epithelium Macrophages Liver, spleen

炎症

absorption storage

RoxadustatReducesHepcidin

DecreasedHepcidinImprovesIronAvailabilityandReducesESAResistanceCKD-DDPa3entsPreviouslyTreatedwithEPOandRandomized(Study040a)(Conversion,previouslyonESA)

CKD-DD Newly Initiated Dialysis (Study 053, ESA naive)

Mean (±SE) Hepcidin (ng/mL)

n=52

n=52

Baseline Week 7 Baseline Week 7

Roxadustat 2 mg/kg

EPO Control

¹ p-value: change in hepcidin level at Week 7 from baseline in roxadustat vs EPO

n=9 n=9


Roxadustat

Source: Provenzano et al. 2016, Clin J Am Soc Nephrol (in press) doi: 10.2215 Source:Besarabetal(2016)JAmSocNephrol.27:1225-1233

•  EPOdoserequirementvsCRP •  RoxadoserequirementvsbaselineCRP

HigherESAbutNOTRoxadustatDosesRequiredinPresenceofInflamma0on

Study 040B: Epoetin Alfa Arm Study 040B: Roxadustat Arm

Source: Provenzano et al. 2016, Clin J Am Soc Nephrol (in press) doi: 10.2215

0

100

200

300

400

500

600

0.1 1 10 100

Pre-

Enro

llmen

t Ave

rage

Wee

kly E

poet

in A

lfa D

ose (

IU/kg

)

Baseline CRP (mg/L)

LR

R2=0.106 P=0.023

N=49*

0

1

2

3

4

5

6

7

8

9

0.1 1 10 100

Aver

age W

eekly

Rox

adus

tat D

ose L

ast 7

of 1

9 Wee

ks (

mg/

kg)

Average CRP (mg/L) Last 7 of 19 Weeks

LR

R2=0.004 p=0.66

N=49*

PHICorrectsAnemiainNewlyIni0atedDialysisPa0entswithoutIVIron

Source:Besarabetal(2016)JAmSocNephrol.27:1225-1233

* p<0.05 compared to IV iron and oral iron

* *

Weeks on Treatment

Hemoglobin (g/dL)

1Cmaxdataforroxadustates0matedforasubsetof243pa0entswhoachievedHbresponseandweredosedatexpectedtherapeu0cdoses.2Milledge&Cotes(1985)JApplPhysiol59:360.3Goldbergetal.(1993),ClinBiochem26:183,Maedaetal.(1992)IntJHematol55:111.4Katoetal.(1994)RenFail16:645.5BasedonFlahertyetal.(1990)ClinPharmacolTher47:557.

0

1,000

2,000

3,000

4,000

5,000

6,000

EPOCmax(mIU/mL)

Al0tude2 BloodLoss3 PulmEdema4

0.99 1.20 1.60 20 44 930.16 3.86

DoseDistribu3onbyPercen3le

mg/kg/dose

Min 25% 50% 75% Max

DoseDistribu3onbyPercen3le(DOPPSQ4,2011)

U/kg/doseTIW

25% 50% 75% 95%

197

PHIAchievesTargetHbwithinornearPhysiologicEPOCmaxLevels

ROXADUSTAT1(TargetHb11to13g/dL)

PHYSIOLOGICALADAPTATION

(U.S.ESALabel:Hb10to11g/dL)

ESA5

PHIReducesHepcidin

DecreasedHepcidinImprovesIronAvailabilityandReducesESAResistanceCKD-DDPa3entsPreviouslyTreatedwithEPOandRandomized(Study040a)(Conversion,previouslyonESA)

CKD-DD Newly Initiated Dialysis (Study 053, ESA naive)


n=52

n=52

Baseline Week 7 Baseline Week 7

Roxadustat 2 mg/kg

EPO Control

¹ p-value: change in hepcidin level at Week 7 from baseline in roxadustat vs EPO

n=9 n=9


Roxadustat

Source: Provenzano et al. 2016, Clin J Am Soc Nephrol (in press) doi: 10.2215 Source:Besarabetal(2016)JAmSocNephrol.27:1225-1233

•  EPOdoserequirementvsCRP •  RoxadoserequirementvsbaselineCRP

HigherESAbutNOTPHIDosesRequiredinPresenceofInflamma0on

Study 040B: Epoetin Alfa Arm Study 040B: Roxadustat Arm

Source: Provenzano et al. 2016, Clin J Am Soc Nephrol (in press) doi: 10.2215

0

100

200

300

400

500

600

0.1 1 10 100

Pre-

Enro

llmen

t Ave

rage

Wee

kly E

poet

in A

lfa D

ose (

IU/kg

)

Baseline CRP (mg/L)

LR

R2=0.106 P=0.023

N=49*

0

1

2

3

4

5

6

7

8

9

0.1 1 10 100

Aver

age W

eekly

Rox

adus

tat D

ose L

ast 7

of 1

9 Wee

ks (

mg/

kg)

Average CRP (mg/L) Last 7 of 19 Weeks

LR

R2=0.004 p=0.66

N=49*

Contents



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