AnemiaAnemia of Chronic Kidney Disease y

BehzadBehzad PoopakPoopak, DCLS PhD., DCLS PhD.Tehran Medical Branch Tehran Medical Branch –– Islamic Azad UniversityIslamic Azad University

bpoopak@yahoo.combpoopak@yahoo.com

Chronic Kidney Disease (CKD)Chronic Kidney Disease (CKD)Chronic Kidney Disease (CKD)Chronic Kidney Disease (CKD)

National Kidney Foundation (NKF) National Kidney Foundation (NKF) classification system classification system 2002 2002 for staging CKDfor staging CKDyy g gg gCKD previously called:CKD previously called:

Chronic renal failureChronic renal failureChronic renal failureChronic renal failurePrePre--ESRD (ESRD (End Stage Renal DiseaseEnd Stage Renal Disease))Renal failureRenal failureRenal failureRenal failureRenal damageRenal damageKid diKid diKidney diseaseKidney disease

KDOQI Defines CKDKDOQI Defines CKDKidney Disease Outcomes Quality Initiative

Stages of Chronic Kidney DiseaseStages of Chronic Kidney Diseaseg yg yNKF Kidney Disease Outcomes Quality Initiative (K/DOQI): CKD Stages

Stage DescriptionGFR

(mL/min/1.73 m2)

1 Kidney damage with ≥90

y gnormal or ↑ GFR ≥90

2 Kidney damage withmild ↓ GFR 60-89

3 Moderate ↓ GFR 30-59

4 Severe ↓ GFR 15-29

5 Kidney failure <15 (or dialysis)

Reference: 1. National Kidney Foundation. Am J Kidney Dis. 2002;39(suppl 1):S1-S266.

NKF-KDOQI Stages of CKDNKF-KDOQI Stages of CKDNKF KDOQI Stages of CKDNKF KDOQI Stages of CKD

CKD Continuum

Renal Insufficiency ESRD

1Kidney Damage

2Kidney Damage

3Moderate

GFR

4Severe GFR

5KidneyFail reDamage

with normal or GFR

Damage with Mild GFR

GFR GFR Failure

50 40 30 20 <15 or60708090Dialysis/

NKF-K/DOQI. Am J Kidney Dis. 2002;37:S1-S266.

GFR (mL/min/1.73 m2)y

Transplantation (RRT)

AnemiaAnemiaAnemiaAnemia

History and DefinitionHistory and Definitionyy

Anemia is one of the most common manifestationsAnemia is one of the most common manifestationsAnemia is one of the most common manifestations Anemia is one of the most common manifestations of CKD.of CKD.

Untreated anemia can, depending on its severity, be Untreated anemia can, depending on its severity, be associated with a number of abnormalities :associated with a number of abnormalities :

- Decreased oxygen delivery to the tissues - Increased cardiac output and cardiomegaly; - Decreased cognition and mental acuity; and - Overall decrease in patient welfare

Defining Anemia (NKF)Defining Anemia (NKF)

Group of diseases characterized by a decrease p yin either Hb, Hct or RBC that reduce the oxygen carrying capacity of the blood.

Diagnose anemia if:Diagnose anemia if:-- HbHb << 12 12 g/g/dLdL ((adult females)adult females)

HbHb 1313 55 //dLdL (( d lt l )d lt l )-- HbHb << 1313..5 5 g/g/dLdL ((adult males)adult males)In patients with CKD the hemoglobin should be In patients with CKD the hemoglobin should be 1111 g/g/dLdL or greateror greater11 11 g/g/dLdL or greateror greater

KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis 47:S1-S146, 2006 (suppl 3)

World Health Organi ationWorld Health Organi ationWorld Health OrganizationWorld Health Organization

WHO d fi iti f iWHO d fi iti f iWHO definition of anemia:WHO definition of anemia:MalesMales HgbHgb< < 13 13 gm/gm/dLdLFemalesFemales HgbHgb < < 12 12 gm/gm/dLdL

W ld H lth O i ti N t iti l i t f WHO S i tifi GWorld Health Organization: Nutritional anemia: report of a WHO Scientific Group.Geneva, Switzerland: World Health Organization.

Cause of Anemia in Long Term CareCause of Anemia in Long Term Caregg

C13.2

Chronic diseaseCKDUnknownUnknownFe, B12, folateOther

15.9

65.6 1 3

4.0

n=481

LTC=long-term care.

1.3

LTC long term care.

Reference: Chernetsky et al. Harefuah. 2002;141:591-594.

Signs and Symptoms of Anemia Are Nonspecific

Signs and Symptoms of Anemia Are NonspecificNonspecific Nonspecific

Cardiorespiratory system• Dyspnea

Central nervous system (CNS)

• Tachycardia • Systolic ejection murmur• Palpitations• Cardiac enlargement

y ( )• Fatigue• Headache• Dizziness• Syncope

• Hypertrophy• Wide pulse pressure• Hypotension• Orthostasis

• Depression• Impaired cognition

Gastrointestinal system• Anorexia• Nausea

Vascular system• Cold intolerance• Edema• Pallor of skin, mucous

Genital tract• Impotence

membranes, and conjunctivae

Reference: Morley et al. Ann Long-Term Care. 2003:S1-S21. Available at: http://www.annalsoflongtermcare.com/supplements.cfm. Accessed February 6, 2007.

Adverse Outcomes Associated With Anemia in Older Adults

Adverse Outcomes Associated With Anemia in Older Adultsin Older Adultsin Older Adults

Decreased muscleDecreased muscle strength and

physical function1

I d i kIncreased risk of stroke10

Increased heart disease2

AnemiaIncreased frequency

of hospital admission7,8

and death7-9Increased falls3 and fall-related injuries4

Cognitiveimpairment5,6

References: 1. Penninx et al. J Am Geriatr Soc. 2004;52:719-724. 2. Zeidman et al. Isr Med Assoc J. 2004;6:16-18. 3. Guse et al. WMJ. 2003;102:37-42. 4. Herndon et al. J Am Geriatr Soc. 1997;45:739-743. 5. Zuccala et al. Am J Med. 2005;118:496-502. 6. Arygyriadou et al. BMC Fam Pract. 2001;2:5. 7. Felker et al. J Cardiol. 2003;92:625-628. 8. Li et al. Kidney Int. 2004;65:1864-1869. 9. van Dijk et al. J Am Geriatr Soc. 2005;53:660-665. 10. Abramson et al. Kidney Int. 2003;64:610-615.

A i f CKDA i f CKDAnemia of CKDAnemia of CKD

Anemia Prevalence by CKD StageAnemia Prevalence by CKD Stage(%

)

70NHANES IIINHANES 1999-2000

nem

ia*

40

50

60

With

An

20

30

40

atie

nts

W

0

10

1 2 3 4 5

*NHANES participants aged ≥20 y with anemia as defined by WHO criteria: hemoglobin (Hgb) <12 g/dL for women, and Hgb <13 g/dL for men.

Pa

1 2 3 4-5CKD Stage

g g gUSRDS 2004 Annual Data Report. The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government. Available at: www.usrds.org. Accessed 3/28/05.

© 2005 The Johns Hopkins University School of Medicine.

Anemia Worsens as Kidney Function Declines

Anemia Worsens as Kidney Function DeclinesDeclinesDeclines

90100

%) Hb LevelsHb Levels

1515

10

607080

Ane

mia

(% Hb=Hb=1111--1212 g/dL (n=g/dL (n=181181))Hb=Hb=1010--11 11 g/dL (n=g/dL (n=105105))Hb=<Hb=<10 10 g/dL (n=g/dL (n=315315))

62

817

15

30405060

ence

of A

g (g ( ))

14 20

4362

895

102030

Prev

ale

0<2 2.0-2.9 3.0-3.9 >4

Serum Creatinine Level (mg/dL)

Reference: Adapted from Kausz et al. Reference: Adapted from Kausz et al. Dis Manage Health Outcomes.Dis Manage Health Outcomes. 20022002;;1010::505505--513513..

Etiology and PathogenesisEtiology and Pathogenesis

The primary cause of the anemia is The primary cause of the anemia is decreased production of EPO decreased production of EPO

A diminished capacity to excrete A diminished capacity to excrete potentially toxic metabolic potentially toxic metabolic end end products may contribute to the anemia :products may contribute to the anemia :

-- by shortening the red cell life spanIn adults and children, EPO is produced

primarily by the peritubular interstitial cells of the-- by shortening the red cell life span, - by marrow suppression, and - by increasing the risk of blood loss.

ConcomitantConcomitant inflammatoryinflammatory conditions and/orconditions and/or malnutritionmalnutrition maymay

primarily by the peritubular interstitial cells of the kidney; therefore, the loss of functioning kidney parenchyma results in impaired EPO generation. Concomitant Concomitant inflammatoryinflammatory conditions and/or conditions and/or malnutritionmalnutrition may may aggravate the anemia and impair its response to therapy.aggravate the anemia and impair its response to therapy.

Inflammatory conditions lead to Inflammatory conditions lead to increased increased hepcidinhepcidin production production and and

p y p gUnder normal conditions, circulating

erythropoietin levels are low, but are augmented yy pp pphepcidinhepcidin inhibits inhibits enterocyteenterocyte iron absorption in the gut and iron absorption in the gut and macrophage iron release through macrophage iron release through ferroportinferroportin ..

D d i i ib h iD d i i ib h i

as much as 100- to 1000-fold in response to anemia or tissue hypoxia in a process mediated by hypoxia inducible factor 1Decreased serum iron concentration may contribute to the anemia Decreased serum iron concentration may contribute to the anemia and limit the response to exogenous EPO administration.and limit the response to exogenous EPO administration.

by hypoxia-inducible factor 1.

ErythropoietinErythropoietin

Inverse correlation bet. EPO & Inverse correlation bet. EPO & rbcrbc massmassEPO immunoassay, EPO immunoassay, two two –– site ELISAsite ELISAWHO calibrated StandardWHO calibrated StandardWHO calibrated StandardWHO calibrated StandardSpecimen: Specimen: SerumSerumThe best time: The best time: 77::30 30 AM AM -- 1212::00 00 noonnoon, Diurnal , Diurnal

i tii tivariationvariationBlood should be clotted at Blood should be clotted at 22--88ooC, if clotted at RT C, if clotted at RT may decrease up to may decrease up to 3030%%Avoid grossly Avoid grossly hemolyzedhemolyzed or grossly or grossly lipemiclipemic samplesampleRIRI: : 33..2222--3131..9 9 mIUmIU/ml/ml

Common pathogenic mechanisms foranemia of CKD/ESRD

Common pathogenic mechanisms foranemia of CKD/ESRDanemia of CKD/ESRDanemia of CKD/ESRD

Patients with CKD/ESRD may developPatients with CKD/ESRD may developPatients with CKD/ESRD may develop Patients with CKD/ESRD may develop anemia on the basis of any etiology, including anemia on the basis of any etiology, including ::Vitamin BVitamin B12 12 and folic acid deficiency, and folic acid deficiency, inherited inherited hemoglobinopathyhemoglobinopathy, , bleeding, bleeding, hemolysishemolysis, , medicationsmedicationsmedications, medications, malignancy,malignancy,and bone marrow infiltration.and bone marrow infiltration.and bone marrow infiltration.and bone marrow infiltration.

Factors That Cause or Contribute t A i i CKD

Factors That Cause or Contribute t A i i CKD

α

to Anemia in CKDto Anemia in CKD•• Erythropoietin deficiency (insufficient production Erythropoietin deficiency (insufficient production

of endogenous erythropoietin)of endogenous erythropoietin)•• Iron deficiencyIron deficiency•• Acute/chronic inflammatory conditions Acute/chronic inflammatory conditions •• Severe hyperparathyroidismSevere hyperparathyroidism

Al i t i itAl i t i it•• Aluminum toxicityAluminum toxicity•• FolateFolate deficiencydeficiency

Decreased RBC survivalDecreased RBC survival•• Decreased RBC survivalDecreased RBC survival•• HemoglobinopathiesHemoglobinopathies ((egeg, , alphaalpha--thalassemiathalassemia, ,

sicklesickle--cell anemia)cell anemia)sicklesickle--cell anemia)cell anemia)KDOQI. Am J Kidney Dis. 2001;37(1 Suppl 1):S182-238.Agarwal AK. J Am Med Dir Assoc. 2006;7(9 Suppl):S7-S12.

Common pathogenic mechanisms foranemia of CKD/ESRD

Common pathogenic mechanisms foranemia of CKD/ESRDanemia of CKD/ESRDanemia of CKD/ESRD

ESA: Erythropoietic Stimulating Agent

CHRONIC KIDNEY DISEASE

EPO defic. Iron defic. Erythropoiesis suppr. Inflammation Oxidative stress

ANEMIA

Hemolysis Vitamin defic. Malnutrition HyperPTH Aluminum ? ACEI

CHRONIC KIDNEY DISEASE

Healthy RBC ProductionR i EPO d IRequires EPO and Iron

Bone Marrow CirculationBone Marrow CirculationErythropoietin Iron

Stem Cell BFU-E CFU-E RBCsReticuloctyesPro-erythroblast

0 25211915Erythropoietin levels are not routinely used in distinguishing

erythropoietin deficiency from other causes of anemia in patients with CKD in most clinical settings and theirTime to Mature Cell Development, days

Brock. Iron Metabolism in Health and Disease. W.B. Saunders Co; 1994.

patients with CKD in most clinical settings and their measurement is generally not recommended.

Approach to normocytic anemiaApproach to normocytic anemianormocytic anemia

Is there increased red cell production?

normocytic anemia

check reticulocyte count

increased normal or decreased

Is there evidence of hemolysis?

Is there evidence of:- renal failure anemia of renal failure

d i f il i f d i f ilhemolysis?

yes

- endocrine failure anemia of endocrine failure- chronic inflammation anemia of chronic disease

noconsider

hemolytic anemia

recent bleed

consider bone marrow failure

bone marro in estigationbone marrow investigation

Evaluation of AnemiaEvaluation of AnemiaComplete blood count

Erythrocyte indices

Reticulocyte countSerum ferritin

Iron parametersTransferrin saturation

Reticulocyte Hb content

CRP

Stool occult blood

Hypochromic RBC 

PTH

Vitamin B 12, folate, copper

PTH

Hemolysis

A step-by-step guide to CKD anemia diagnosis and treatment

A step-by-step guide to CKD anemia diagnosis and treatmentgg

Diagnosis of anemiaDiagnosis of anemia

Diagnose anemia in adults and children >Diagnose anemia in adults and children >1515 yearsyearsDiagnose anemia in adults and children Diagnose anemia in adults and children 15 15 years years with CKD when the with CKD when the HbHb concentration is <concentration is <1313..0 0 g/dl g/dl (<(<130 130 g/l) in males and <g/l) in males and <1212..0 0 g/dl (<g/dl (<120 120 g/l) in g/l) in females. (Not Graded)females. (Not Graded)Diagnose anemia in children with CKD if Diagnose anemia in children with CKD if HbHbconcentration is :concentration is :

<<1111..0 0 g/dl (<g/dl (<110 110 g/l) in children g/l) in children 00..55––5 5 years, years, <<1111..5 5 g/dl (g/dl (115 115 g/l) in children g/l) in children 55––12 12 years, andyears, and<<1212..0 0 g/dl (g/dl (120 120 g/l) in children g/l) in children 1212––15 15 years. (Not years. (Not

Graded)Graded)

Assessment of Anemia in CKDAssessment of Anemia in CKDTest Test HbHb at least annually in all patients, regardless of at least annually in all patients, regardless of stage or cause of CKDstage or cause of CKDstage or cause of CKD stage or cause of CKD HctHct is a derived value, affected by plasma water, and, therefore, can be imprecise is a derived value, affected by plasma water, and, therefore, can be imprecise

as a direct assessment of as a direct assessment of erythropoiesiserythropoiesis. In contrast to . In contrast to HctHct, , HbHb values are values are absolute and directly impacted by decreased erythropoietin production by the absolute and directly impacted by decreased erythropoietin production by the kidkid 11kidneykidney11

Assessment should include the following tests:Assessment should include the following tests:A complete blood countA complete blood countA complete blood countA complete blood countAbsolute Absolute reticulocytereticulocyte countcountSerum Serum ferritinferritin to assess iron storesto assess iron storesSerum Serum transferrintransferrin saturation (TSAT) or content of saturation (TSAT) or content of HbHb in in reticulocytesreticulocytes to to

d f i fd f i f th i ith i iassess adequacy of iron for assess adequacy of iron for erythropoiesiserythropoiesisStool for occult bloodStool for occult blood22

References: 1 National Kidney Foundation Am J Kidney Dis 2006;47(suppl 3):S1 S145References: 1. National Kidney Foundation. Am J Kidney Dis. 2006;47(suppl 3):S1-S145. 2. National Kidney Foundation. Available at: http://www.kidney.org/professionals/kdoqi/guidelines_updates/doqiupan_i.html.

E hi t & i l t d bE hi t & i l t d bEcchinocyte & spiculated rbcEcchinocyte & spiculated rbc

EcchinocytesEcchinocytes

Frequency of testing for anemiaFrequency of testing for anemiaFor CKD patients For CKD patients without anemia without anemia measure measure HbHbconcentration when clinically indicated and (Not concentration when clinically indicated and (Not Graded):Graded):At least At least annuallyannually in patients with in patients with CKD CKD 33At least At least twice per year twice per year in patients with in patients with CKD CKD 44––5 5 NDNDAt least At least every every 3 3 months months in patients with in patients with CKD CKD 55HD HD yy ppand and CKD CKD 55PDPD

Frequency of testing for anemiaFrequency of testing for anemiaFrequency of testing for anemiaFrequency of testing for anemia

For CKD patients For CKD patients with anemia with anemia not being treated not being treated with an ESA, measure with an ESA, measure HbHb concentration when concentration when clinically indicated and (Not Graded):clinically indicated and (Not Graded):At least At least every every 3 3 months months in patients with in patients with CKDCKD

33––55NDND and and CKD CKD 55PDPDAt least At least monthlymonthly in patients with in patients with CKD CKD 55HDHD

Diagnostic and monitoringDiagnostic and monitoringDiagnostic and monitoring considerations

Diagnostic and monitoring considerations

Iron stores should be reassessed Iron stores should be reassessed 11--2 2 months months following the following the initiation of ESA therapy because brisk initiation of ESA therapy because brisk erythropoiesiserythropoiesisrapidly consumes body iron stores and repletion should rapidly consumes body iron stores and repletion should p y y pp y y pbe administered as indicated. be administered as indicated.

OnceOnce HbHb levels, ESA dose, and iron stores have stabilized,levels, ESA dose, and iron stores have stabilized,Once Once HbHb levels, ESA dose, and iron stores have stabilized, levels, ESA dose, and iron stores have stabilized, iron monitoring iron monitoring can be spaced out to can be spaced out to every every 3 3 monthsmonths, but , but more frequent monitoring is indicated when more frequent monitoring is indicated when HbHb levels levels fall, ESA dose requirements rise, or iron stores become fall, ESA dose requirements rise, or iron stores become , q ,, q ,marginal. marginal. In In hemodialysishemodialysis patients, more frequent monitoring may patients, more frequent monitoring may be indicated given the frequent blood loss incurred.be indicated given the frequent blood loss incurred.g qg q

Dietary restrictionsAnorexia

Decrease in oral iron intakeMalnutritionInflammation

Phosphate binders

Blood loss in HDBlood sampling

GI bleeding

Decrease in IRON DEFICIENCY

Decrease in intestinal

Iron absorption

Chronic blood loss

Stimulation of erythropoiesis by ESA

erythropoiesis-stimulating agent (ESA) therapy

Test for functional iron deficiency with Test for functional iron deficiency with ferritin and TSAT or ferritin and %HRCferritin and TSAT or ferritin and %HRC

Functional iron deficiency is defined as the presence of adequate bone marrow iron stores, but an impaired ability to ymobilize these stores for erythropoiesis in the presence of the stimulating effect of an ESA

Hepcidin Regulates Cellular Iron Export Into Plasma

Ganz, T. J Am Soc Nephrol 2007;18:394-400

Hepcidin as the Main RegulatorHepcidin as the Main Regulator of Systemic Iron Homeostasis

Young, B. et al. Clin J Am Soc Nephrol 2009;4:1384-1387

Key goals in managing anaemia of Key goals in managing anaemia of CKDCKD

increase exercise capacityincrease exercise capacity

improve cognitive function

regulate and/or prevent left ventricular hypertrophyyp p y

prevent progression of renal disease

reduce risk of hospitalisation

decrease mortalitdecrease mortality

Treatment for Anemia of CKD

Treatment for Anemia of CKDCKDCKD

Replete iron stores to maintain:Replete iron stores to maintain:Replete iron stores to maintain:Replete iron stores to maintain:TSAT TSAT >> 2020% % andandSerumSerum ferritinferritin >>100100ng/mlng/mlSerum Serum ferritinferritin >>100100ng/mlng/ml

Consider Consider erythropoiesiserythropoiesis--stimulating agent (ESA)stimulating agent (ESA)C ti t l t i t t t tC ti t l t i t t t tContinue to evaluate responsiveness to treatmentContinue to evaluate responsiveness to treatmentWhen treating with ESA, avoid When treating with ESA, avoid HgbHgb >> 12 12 gm/gm/dLdL

Anemia of CKD ManagementAnemia of CKD Management

Supplement iron; most patients should receive oral iron Supplement iron; most patients should receive oral iron supplement to prevent the development of iron deficiencysupplement to prevent the development of iron deficiencysupplement to prevent the development of iron deficiency supplement to prevent the development of iron deficiency even if iron studies are normal at initiation of therapy*even if iron studies are normal at initiation of therapy*Select ESA therapySelect ESA therapypypy

EpoetinEpoetin alfaalfaDarbepoetinDarbepoetin alfaalfa

Monitor Monitor HgbHgb, adjust dose by , adjust dose by 2525% no more frequently than % no more frequently than monthly to reach and maintain targetmonthly to reach and maintain target

*Wish JB, Coyne DW. May Clin Proc.2007;82:1371-80.

The Effect of ESAs on The Effect of ESAs on ErythropoiesisErythropoiesis

ReticulocyteCFU-EBFU-E Normoblast

Stem cell

Erythropoietin response ability

Hb Target and ESAsHb Target and ESAsgg

Consider risk to benefitConsider risk to benefitHgbHgb targetstargets

1111--12 12 g/g/dLdL per per 2007 2007 NKF KDOQI guidelinesNKF KDOQI guidelines1010--12 12 g/g/dLdL per FDA package insertsper FDA package insertsDo not exceed Do not exceed HgbHgb >>12 12 g/g/dLdL; adjust dose as “; adjust dose as “HbHbapproaches approaches 12 12 gm/gm/dLdL””

Monitor Monitor HbHb::Weekly: Weekly: darbepoetindarbepoetinTwice weekly: Twice weekly: epoetinepoetin

Black Box WarningBlack Box Warning

Renal FailureRenal Failure: Patients experienced greater : Patients experienced greater risk for death and serious cardiovascular risk for death and serious cardiovascular events when administered ESAs to a target events when administered ESAs to a target higher versus lower hemoglobin level in two higher versus lower hemoglobin level in two li i l t dili i l t diclinical studies. clinical studies.

Individualize dosing to achieve and Individualize dosing to achieve and maintain a target hemoglobin within themaintain a target hemoglobin within themaintain a target hemoglobin within the maintain a target hemoglobin within the range of range of 10 10 to to 12 12 g/g/dLdL. .

Aranesp [package insert] November 2007Aranesp [package insert]. November 2007.Epogen [package insert]. November 2007.Procrit [package insert]. November 2007

Hb maintenance algorithm (assumes ESA therapy and maintenance i.v. iron)

Hb maintenance algorithm (assumes ESA therapy and maintenance i.v. iron)(assumes ESA therapy and maintenance i.v. iron)(assumes ESA therapy and maintenance i.v. iron)

Measure Hb

Hb < 11 g/dl Hb 11–12 g/dl Hb 12–15 g/dl Hb > 15 g/dl

↑ ESA dose/frequency as per schedule

No changeunless Hb

Considerstopping i.v.iron. ↓ ESA Stop i.v. iron.

Considerunless Hbrising by

1/g/dl/month. Check Hb

rising by1g/dl/month

in which case consider

dose/frequency as per schedule

unless Hb falling by more

Consider stopping

ESA or halvedose/frequency.

Check Hb in

If Hb ispersistently low

as perSchedule.

ESA doseadjustment

than 1g/dl/month. Check Hb as per schedule.

Check Hb in 2 weeks.see poor

response algorithm

Ferritin < 200 µg/l?

Hypo responsiveness to ESAsHypo responsiveness to ESAsHypo-responsiveness to ESAsHypo-responsiveness to ESAsPOTENTIAL CAUSESPOTENTIAL CAUSES

Missed dosesMissed dosesInadequate iron storesInadequate iron stores

Iron deficiency is present in Iron deficiency is present in 2525--3737..55% of patients and is a common % of patients and is a common cause of hyporesponsecause of hyporesponse11cause of hyporesponsecause of hyporesponse

Drug/disease interactionsDrug/disease interactionsRemember, iron needs an acidic environment to be maximally Remember, iron needs an acidic environment to be maximally absorbedabsorbed

BB f l tf l t d fi i id fi i iBB12 12 or or folatefolate deficienciesdeficienciesProtein deficienciesProtein deficienciesOccult blood lossOccult blood lossInfection/inflammation processesInfection/inflammation processesppCoexisting medical conditionsCoexisting medical conditions

Malignancies, hematological disordersMalignancies, hematological disordersHemolysisHemolysis

1. Agarwal AK. J Am Med Dir Assoc. 2006 Nov;7(9 Suppl):S7-S12.2. KDOQI. Am J Kidney Dis. 2001;37(1 Suppl 1):S182-238.

3. Procrit [package insert]. November 2007.4. Aranesp [package insert]. November 2007.

ESA MonitoringESA MonitoringHbHb “at regular intervals” once stabilized“at regular intervals” once stabilized11,,22

CBC with differential and platelet count regularlyCBC with differential and platelet count regularlyCBC with differential and platelet count regularlyCBC with differential and platelet count regularlyBlood pressure should be controlled adequately Blood pressure should be controlled adequately before initiation of therapybefore initiation of therapybefore initiation of therapybefore initiation of therapyFe studies (TSAT, Fe studies (TSAT, ferritinferritin) prior to and during ) prior to and during therapytherapypypySerum chemistry should be checked regularly Serum chemistry should be checked regularly (BUN, (BUN, creatininecreatinine, phosphorus, uric acid, K+), phosphorus, uric acid, K+)11p pp p

References: 1. Procrit [package insert]. Raritan, NJ: Ortho Biotech Products, LP; 2008. Available at: www.procrit.com/procrit/. Accessed October 23, 2008. 2. Aranesp [package insert]. Thousand Oaks, CA: Amgen Inc; 2008. Available at: www.aranesp.com/. Accessed October 23, 2008.

Thank you,Any

more tomore to discuss?