Management of Management of Anemia in Anemia in

Chronic Kidney Chronic Kidney DiseaseDisease

Dr. Dr.

OverviewOverview

CKDCKD AnemiaAnemia Anemia of CKDAnemia of CKD Consultant pharmacist challenges Consultant pharmacist challenges

with MRR for dialysis patientswith MRR for dialysis patients Managing and treating patients on Managing and treating patients on

dialysisdialysis Cases for reviewCases for review

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

in the U.S.in the U.S. National Kidney Foundation (NKF) National Kidney Foundation (NKF)

classification system 2002 for staging classification system 2002 for staging CKDCKD

CKD previously called:CKD previously called: Chronic renal failureChronic renal failure Pre-ESRDPre-ESRD Renal failureRenal failure Renal damageRenal damage Kidney diseaseKidney disease

KDOQI Defines CKDKDOQI Defines CKD

Stages of Chronic Stages of Chronic Kidney DiseaseKidney Disease

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

Stage DescriptionGFR

(mL/min/1.73 m2)

1 Kidney damage with normal or ↑ GFR

≥902 Kidney damage

withmild ↓ GFR

60-89

3 Moderate ↓ GFR 30-59

4 Severe ↓ GFR 15-29

5 Kidney failure <15 (or dialysis)

NKF Kidney Disease Outcomes Quality Initiative (K/DOQI): CKD Stages1

NKF-KDOQI Stages of NKF-KDOQI Stages of CKDCKD

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

50 40 30 20 <15 or

GFR (mL/min/1.73 m2)

1

Kidney Damage

with normal or GFR

2

Kidney Damage with Mild GFR

3

Moderate GFR

4

Severe GFR

60708090

5

KidneyFailure

CKD Continuum

Renal Insufficiency ESRD

Dialysis/Transplantation (RRT)

Markers of Renal Markers of Renal FunctionFunction

Serum creatinineSerum creatinine Cockcroft-Gault EquationCockcroft-Gault Equation eCrCleCrCl MDRD EquationMDRD Equation eGFReGFR

Calculating Creatinine Calculating Creatinine ClearanceClearance

Cockcroft-Gault Equation

CrCl men = (140 - Age) x LBW

Scr x 72

CrCl women = CrCl men x 0.85

Modification of Diet in Renal Disease Equation (MDRD)

CrCl men = (Scr) -1.154 x (age) -0.203

CrCl women = CrCl men x 0.742

CrCl African American = CrCl men x 1.210

http://www.mdrd.com/

9

USRDS: ESRD Incidence USRDS: ESRD Incidence by Ageby Age

Patients Age 65 Years or Older Are More Than Twice as Likely to Have ESRD as People Under Age 50 Years1

Reference: 1. United States Renal Data System. 2007 annual data report reference tables: incidence. Available at: http://www.usrds.org/2007/ref/A_incidence_07.pdf.

Adapted from the United States Renal Data System (USRDS).1

In LTC Residents, the Prevalence In LTC Residents, the Prevalence of CKD Increases With Ageof CKD Increases With Age

0

1

2

3

4

5

6

65-74 75-84 85-94 95+

Men

Women

MDRD=Modification of Diet in Renal Disease.

Reference: Garg et al. Kidney Int. 2004;65:649-653.

40% of the population had a GFR of <60 mL/min/1.73 m2 (MDRD)

Age in Years

Ag

e-R

elat

ed P

reva

len

ceo

f L

ow

GF

R (

%)

n=646

n=472

n=2644n=1061

n=3354

n=977

n=671

n=106

n=9931

Almost One Half of All LTC Almost One Half of All LTC Residents Have GFR <60 Residents Have GFR <60

mL/min/1.73 mmL/min/1.73 m22

Residents with CKD (GFR <60 mL/min/1.73 m2)

44%

Residents without CKD

56%

SCr=serum creatinine.

Reference: Van Vleet et al. Poster presented at: American Geriatric Society Annual Meeting; May 11-15, 2005; Orlando, Fla.

44%

56%

N=4240 (residents with SCr, calculating GFR using MDRD)N=4240 (residents with SCr, calculating GFR using MDRD)

CKD CKD Risk FactorsRisk Factors

Contributors to Renal Contributors to Renal Function DeclineFunction Decline

Decline in kidney weight, loss of nephronsDecline in kidney weight, loss of nephrons Decline in renal perfusionDecline in renal perfusion Decline in GFRDecline in GFR

Est healthly adults lose 8-10ml/min of GFR Est healthly adults lose 8-10ml/min of GFR every decade of life beginning around age 30every decade of life beginning around age 30

Decrease in ability to concentrate urineDecrease in ability to concentrate urine Decreased reabsorption of sodiumDecreased reabsorption of sodium Decreased bladder capacityDecreased bladder capacity

Beck LH. Long-term Care Forum. 5(3) 1995.

Risk Factors for ESRDRisk Factors for ESRD25 Year Follow-up25 Year Follow-up

Retrospective review of 177,570 Retrospective review of 177,570 individuals from large MCO individuals from large MCO (1964-’73)(1964-’73)

Followed for ESRD Tx (USRDS)Followed for ESRD Tx (USRDS) 842 cases ESRD observed842 cases ESRD observed Goal: evaluate value of potential Goal: evaluate value of potential

novel risk factors for ESRD vs novel risk factors for ESRD vs established risk factorsestablished risk factors

Chi-yuan Hsu, MD, MSc; Carlos Iribarren, MD, PhD, et al.Arch Intern Med. 2009;169(4):342-350

Risk Factors for ESRDRisk Factors for ESRD25 Year Follow-up cont’d25 Year Follow-up cont’d

Established Risk Factors for ESRD:Established Risk Factors for ESRD:Gender (M)Gender (M)AgeAgeProteinuria*Proteinuria*DMDMHTNHTNAA raceAA raceElevated SCr (or, decreased GFR)Elevated SCr (or, decreased GFR)Obesity*Obesity*Lower educational attainmentLower educational attainment*most potent risk factors*most potent risk factors

Chi-yuan Hsu, MD, MSc; Carlos Iribarren, MD, PhD, et al.Arch Intern Med. 2009;169(4):342-350

Risk Factors for ESRDRisk Factors for ESRD25 Year Follow-up cont’d25 Year Follow-up cont’d

Independent Risk Factors for ESRD:Independent Risk Factors for ESRD: Lower HgbLower Hgb Higher serum uric acid level (in Higher serum uric acid level (in

females)females) Self-reported Hx of nocturiaSelf-reported Hx of nocturia Family Hx of kidney diseaseFamily Hx of kidney disease

Chi-yuan Hsu, MD, MSc; Carlos Iribarren, MD, PhD, et al.Arch Intern Med. 2009;169(4):342-350

Complications of CKDComplications of CKD CVD CVD

“All patients with chronic kidney disease should be considered in the ‘‘highest risk’’ group for cardiovascular disease, irrespective of levels of traditional CVD risk factors.”

HTN (cause and complication)HTN (cause and complication) Protein energy malnutritionProtein energy malnutrition Central and peripheral neuropathyCentral and peripheral neuropathyAnemiaAnemia ESRDESRD Bone disease/disorders of calcium and Bone disease/disorders of calcium and

phosphorusphosphorusNational Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1)

AnemiaAnemia

Defining Anemia (NKF)Defining Anemia (NKF)

Group of diseases characterized by a Group of diseases characterized by a decrease in either Hgb, Hct or red decrease in either Hgb, Hct or red blood cells (RBC) that reduce the blood cells (RBC) that reduce the oxygen carrying capacity of the blood.oxygen carrying capacity of the blood.

Diagnose anemia if:Diagnose anemia if:- Hemoglobin < 12 g/dL (adult females)- Hemoglobin < 12 g/dL (adult females)- Hemoglobin < 13.5 g/dL (adult males)- Hemoglobin < 13.5 g/dL (adult males)

In patients with CKD the hemoglobin In patients with CKD the hemoglobin should be 11 g/dL or greatershould be 11 g/dL or 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 World Health OrganizationOrganization

WHO definition of anemia:WHO definition of anemia: MalesMales Hgb< 13 gm/dLHgb< 13 gm/dL FemalesFemales Hgb < 12 gm/dLHgb < 12 gm/dL

World Health Organization: Nutritional anemia: report of a WHO Scientific Group.Geneva, Switzerland: World Health Organization, 1968.

Common Causes of Common Causes of Anemia in Elderly Anemia in Elderly

PatientsPatients

Joosten E, et al, Prevalence and causes of anemia in a geriatric hospitalized population. Gerontology 1992; 38:111-117

Anemia of Chronic Anemia of Chronic Inflammation Inflammation (inflammatory (inflammatory disease, infections, CKD)disease, infections, CKD)

30% - 30% - 40%40%

Iron Deficiency AnemiaIron Deficiency Anemia 15% - 15% - 30%30%

Post Hemorrhagic AnemiaPost Hemorrhagic Anemia 5% - 5% - 10%10%

Vitamin B-12 and Folate Vitamin B-12 and Folate Deficiency AnemiaDeficiency Anemia

5% - 5% - 10%10%

Chronic Leukemia or Chronic Leukemia or Lymphoma AnemiaLymphoma Anemia

5%5%

No Identifiable CauseNo Identifiable Cause 15% - 15% - 25%25%

Cause of Anemia in Long Term Cause of Anemia in Long Term CareCare

LTC=long-term care.

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

Chronic disease

Chronic kidney disease

Unknown

Fe, B12, folate

Other

13.2

15.9

65.61.3

4.0

n=481

Signs and Symptoms of Anemia Signs and Symptoms of Anemia Are Nonspecific Are Nonspecific

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

Gastrointestinal system• Anorexia• Nausea

Cardiorespiratory system• Dyspnea• Tachycardia • Systolic ejection murmur• Palpitations• Cardiac enlargement• Hypertrophy• Wide pulse pressure• Hypotension• Orthostasis

Genital tract• Impotence

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

membranes, and conjunctivae

Central nervous system (CNS)

• Fatigue• Headache• Dizziness• Syncope• Depression• Impaired cognition

Laboratory Tests for Laboratory Tests for AnemiaAnemia Reticulocyte count Reticulocyte count (low indicates decreased (low indicates decreased

RBC production; high count may be increased RBC RBC production; high count may be increased RBC destruction)destruction)

Sedimentation rate (ESR): index of Sedimentation rate (ESR): index of inflammationinflammation

Stool for occult blood: evaluates GI lossStool for occult blood: evaluates GI loss Morphology by peripheral smear: size, Morphology by peripheral smear: size,

color, shape of RBCcolor, shape of RBC Hepatic and renal functionHepatic and renal function Thyroid-stimulating hormone (TSH)Thyroid-stimulating hormone (TSH)

Medications That Can Cause Medications That Can Cause AnemiaAnemia

Red blood cell production*

Red blood cell loss (bleeding)

Red blood cell survival

Alcohol AnticoagulantsAnticoagulants High-dose High-dose penicillinpenicillin

H2 blockersH2 blockers Antiplatelet agentsAntiplatelet agents Sulfa agentsSulfa agents

MetforminMetformin AspirinAspirin

PhenobarbitalPhenobarbital BisphosphonatesBisphosphonates

PhenytoinPhenytoin CorticosteroidsCorticosteroids

Proton pump Proton pump inhibitorsinhibitors

Nonsteroidal Nonsteroidal anti-inflammatory anti-inflammatory drugsdrugs

Sulfa agentsSulfa agents

Chemotherapy Chemotherapy agentsagents*Can impair vitamin B*Can impair vitamin B1212 and folate absorption or metabolism, which and folate absorption or metabolism, which impairs red blood cell production. impairs red blood cell production.

Reference: American Medical Directors Association. Clinical Practice Guideline. Columbia, MD: American Medical Directors Association; 2007.

Treating AnemiaTreating Anemia B-12 DeficiencyB-12 Deficiency

B-12 replacementB-12 replacement Oral, sublingual, intranasal, IMOral, sublingual, intranasal, IM

Folic Acid DeficiencyFolic Acid Deficiency Folic acid replacementFolic acid replacement Oral, subcutaneous, IMOral, subcutaneous, IM

Iron DeficiencyIron Deficiency Iron replacement (several salt forms/dose forms) Iron replacement (several salt forms/dose forms)

Oral, IV, IMOral, IV, IM Anemia of Chronic Kidney Disease (CKD)Anemia of Chronic Kidney Disease (CKD)

Erythropoietic Stimulating AgentsErythropoietic Stimulating Agents Epoetin Alfa (EpogenEpoetin Alfa (Epogen™™/Procrit/Procrit™™), Darbepoetin ), Darbepoetin

Alfa (AranespAlfa (Aranesp™™))

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

Assessing AnemiaAssessing Anemia

JM 84 yo femaleJM 84 yo female Dx: anemia, DM, dementia, incontinence, Dx: anemia, DM, dementia, incontinence,

osteoarthritis, osteoporosisosteoarthritis, osteoporosis Recurrent fallsRecurrent falls CNAs report “she won’t use the call CNAs report “she won’t use the call

light”light” What action, What action, in generalin general, should the CP , should the CP

take when requested to review resident take when requested to review resident for falls for an interim MRR?for falls for an interim MRR?

Iron Products and Drug Iron Products and Drug InteractionsInteractions

Avoid administration with calcium, Avoid administration with calcium, antacids, levothyroxine, levodopa, antacids, levothyroxine, levodopa, fluoroquinolones, PPIs, H-2 blockersfluoroquinolones, PPIs, H-2 blockers

Iron and the State Iron and the State Operations Manual (SOM)Operations Manual (SOM)

Iron does not stimulate rbc Iron does not stimulate rbc productionproduction

Iron does not correct anemia that is Iron does not correct anemia that is not caused by iron deficiencynot caused by iron deficiency

Document chronic useDocument chronic use Document doses > once dailyDocument doses > once daily Documentation for “clinical Documentation for “clinical

rationale” may include use of an ESArationale” may include use of an ESA

When is “Enough” Iron When is “Enough” Iron “Too Much”?“Too Much”?

F329 Unnecessary Drugs Table 1 F329 Unnecessary Drugs Table 1 ““Iron therapy is not indicated in anemia Iron therapy is not indicated in anemia

of chronic disease when iron stores and of chronic disease when iron stores and transferrin levels are normal or transferrin levels are normal or elevated”elevated”

““Clinical rationale should be documented Clinical rationale should be documented for long-term use (> 2 months) or > 1 for long-term use (> 2 months) or > 1 daily > 1 week because of side effects daily > 1 week because of side effects and risk of iron accumulation in tissues”and risk of iron accumulation in tissues”

Adverse Outcomes Associated With Adverse Outcomes Associated With Anemia Anemia

in Older Adultsin Older Adults

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.

Decreased muscle strength and

physical function1

Decreased muscle strength and

physical function1

Increased frequency of hospital admission7,8

and death7-9

Increased frequency of hospital admission7,8

and death7-9

Increased risk of stroke10

Increased risk of stroke10

Increased falls3 and fall-related injuries4

Increased falls3 and fall-related injuries4

Increased heart disease2Increased heart disease2

Cognitiveimpairment5,6

Cognitiveimpairment5,6

Anemia

Impact of Anemia on QIsImpact of Anemia on QIs Incidence of new fracturesIncidence of new fractures Prevalence of fallsPrevalence of falls Prevalence of behavioral symptomsPrevalence of behavioral symptoms Prevalence of symptoms of depressionPrevalence of symptoms of depression Incidence of cognitive impairmentIncidence of cognitive impairment Prevalence of weight lossPrevalence of weight loss Prevalence of dehydrationPrevalence of dehydration Incidence of decline in ADLsIncidence of decline in ADLs Prevalence of little or no activityPrevalence of little or no activity Prevalence of psychoactive medication Prevalence of psychoactive medication

useuse

Anemia of CKDAnemia of CKD

Anemia Worsens as Kidney Anemia Worsens as Kidney Function DeclinesFunction Declines

14 20

43

628

8

15

9

17

15

10

5

0

10

20

30

40

50

60

70

80

90

100

<2 2.0-2.9 3.0-3.9 >4

Serum Creatinine Level (mg/dL)

Pre

vale

nce

of

An

emia

(%

)

Reference: Adapted from Kausz et al. Reference: Adapted from Kausz et al. Dis Manage Health Outcomes.Dis Manage Health Outcomes. 2002;10:505-513. 2002;10:505-513.

Hb LevelsHb Levels

Hb=11-12Hb=11-12 g/dL (n=181)g/dL (n=181)

Hb=10-11 g/dL (n=105)Hb=10-11 g/dL (n=105)

Hb=<10 g/dL (n=315)Hb=<10 g/dL (n=315)

Etiology of CKD AnemiaEtiology of CKD Anemia Decreased rbc production due to lack of Decreased rbc production due to lack of

erythropoietin; kidneys responsible for erythropoietin; kidneys responsible for 90% of epo production90% of epo production

Increased rbc destruction due to Increased rbc destruction due to hemolysishemolysis

Increased blood loss due to multiple Increased blood loss due to multiple venipuncturesvenipunctures

Decreased rbc production is present in Decreased rbc production is present in CKD anemia and anemia of chronic CKD anemia and anemia of chronic disease, and both are normochromic, disease, and both are normochromic, normocytic anemiasnormocytic anemiasAnemia of Chronic Disease and Renal Failure. http://emedicine.medscape.com

Accessed Sept 12, 2009

Renal Anaemia

damaged kidneyimpaired production of

erythropoietinreduced number of red

blood cells

anaemia

Erythropoietin

Red blood cells O2 delivery

Erythroidmarrow

Iron

REcells

RE=reticuloendothelial

X

Erythropoietin DeficiencyErythropoietin Deficiency

Adapted from: Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 1998; 334.

Factors That Cause or Factors That Cause or Contribute Contribute

to Anemia in CKDto Anemia in CKD• Erythropoietin deficiency (insufficient Erythropoietin deficiency (insufficient production of endogenous erythropoietin)production of endogenous erythropoietin)

• Iron deficiencyIron deficiency• Acute/chronic inflammatory conditions Acute/chronic inflammatory conditions • Severe hyperparathyroidismSevere hyperparathyroidism• Aluminum toxicityAluminum toxicity• Folate deficiencyFolate deficiency• Decreased RBC survivalDecreased RBC survival• Hemoglobinopathies (eg, Hemoglobinopathies (eg, alphaalpha--

thalassemia, thalassemia, sickle-cell anemia)sickle-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.

α

Key goals in managing anaemia of CKD

increase exercise capacity

improve cognitive function

regulate and/or prevent left ventricular

hypertrophy

prevent progression of renal disease

reduce risk of hospitalisation

decrease mortality

What the recommendations cover

Diagnosis of anaemia of CKDManagement of anaemia of CKDAssessment and optimisation of erythropoiesis Maintaining stable haemoglobinMonitoring of ACKD treatment

Assessment of Anemia in Assessment of Anemia in CKDCKD

Test Hb at least annually in all patients, regardless of Test Hb at least annually in all patients, regardless of stage or cause of CKDstage or cause of CKD Hct is a derived value, affected by plasma water, and, therefore, Hct is a derived value, affected by plasma water, and, therefore,

can be imprecise as a direct assessment of erythropoiesis. In can be imprecise as a direct assessment of erythropoiesis. In contrast to Hct, Hb values are absolute and directly impacted contrast to Hct, Hb values are absolute and directly impacted by decreased erythropoietin production by the kidneyby decreased erythropoietin production by the kidney11

Assessment should include the following tests:Assessment should include the following tests: A complete blood countA complete blood count Absolute reticulocyte countAbsolute reticulocyte count Serum ferritin to assess iron storesSerum ferritin to assess iron stores Serum transferrin saturation (TSAT) or content of Hb in Serum transferrin saturation (TSAT) or content of Hb in

reticulocytes to assess adequacy of iron for erythropoiesisreticulocytes to assess adequacy of iron for erythropoiesis Stool for occult bloodStool for occult blood22

References: 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.

Treatment for Anemia of Treatment for Anemia of CKDCKD

Replete iron stores to maintain:Replete iron stores to maintain: TSAT TSAT >> 20% and 20% and Serum ferritin Serum ferritin >>100ng/ml100ng/ml

Consider erythropoiesis-stimulating Consider erythropoiesis-stimulating agent (ESA)agent (ESA)

Continue to evaluate responsiveness Continue to evaluate responsiveness to treatmentto treatment

When treating with ESA, avoid Hgb > When treating with ESA, avoid Hgb > 12 gm/dL12 gm/dL

Anemia of CKD Anemia of CKD ManagementManagement

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

Select ESA therapySelect ESA therapy Epoetin alfa Epoetin alfa Darbepoetin alfa Darbepoetin alfa

Monitor Hgb, adjust dose by 25% no more Monitor Hgb, adjust dose by 25% no more frequently than monthly to reach and frequently than monthly to reach and maintain targetmaintain target

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

Hgb Target and ESAsHgb Target and ESAs

Consider risk to benefitConsider risk to benefit Hgb targetsHgb targets

11-12 g/dL per 2007 NKF KDOQI 11-12 g/dL per 2007 NKF KDOQI guidelinesguidelines

10-12 g/dL per FDA package inserts10-12 g/dL per FDA package inserts Do not exceed Hgb >12 g/dL; adjust dose Do not exceed Hgb >12 g/dL; adjust dose

as “Hgb approaches 12 gm/dL”as “Hgb approaches 12 gm/dL” Monitor Hgb:Monitor Hgb:

Weekly: darbepoetinWeekly: darbepoetin Twice weekly: epoetinTwice weekly: epoetin

Black Box WarningBlack Box Warning

Renal FailureRenal Failure: Patients experienced : Patients experienced greater risk for death and serious greater risk for death and serious cardiovascular events when cardiovascular events when administered ESAs to a target higher administered ESAs to a target higher versus lower hemoglobin level in two versus lower hemoglobin level in two clinical studies. Individualize dosing to clinical studies. Individualize dosing to achieve and maintain a target achieve and maintain a target hemoglobin within the range of 10 to hemoglobin within the range of 10 to 12 g/dL. Nov 0712 g/dL. Nov 07Aranesp [package insert]. November 2007. Epogen [package insert]. November 2007. Procrit [package insert]. November 2007

Diagnosis of anaemia of CKD in adults

eGFR < 60ml/min/1.73m2

AND Hb ≤ 11 g/dl

No

Consider other causes

Yes

Non renal and haematinic

deficiency excluded?

No

Treat and repeat Hb

Yes

Patient on haemodialysis?

No

See sections 1.2 & 1.3

Yes

See initial management

algorithm

Initial management algorithm

Ferritin < 500 µg/l? NoYes

Ferritin < 200 µg/l?

Yes NoTSAT < 20% Or

%HRC > 6%

NoYes – functional iron deficiency

Assess Hb

ESA (s.c.or i.v.)

Hb > 9 g/dl Hb < 9 g/dl

i.v. iron

ESA (s.c.or i.v.)

and iron

Assess Hb at 6 weeks

Hb < 11 g/dl

Hb > 11 g/dl

Continuemonitoring Hb and iron status

If Hb increase < 1g/dl after 4 weeks, increase

ESA using dose schedule

Assess and optimise erythropoiesis

Iron supplements should be given to maintain serum ferritin levels ESA therapy is appropriate in iron-replete patients where existing comorbidities or prognosis do not negate its effectBenefits of ESA therapy include improved quality of life and physical functioningThere is no evidence to distinguish between ESAs in terms of efficacy

Hb maintenance algorithm (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

unless Hb rising by

1/g/dl/month. Check Hb

as perSchedule.

No changeunless Hbrising by

1g/dl/monthin which case

considerESA doseadjustment

Consider stopping i.v.iron. ↓ ESA

dose/frequency as per schedule

unless Hb falling by more

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

Stop i.v. iron.Consider stopping

ESA or halvedose/frequency.

Check Hb in 2 weeks.

If Hb ispersistently low

see poor response algorithm

Ferritin < 200 µg/l?

Iron dosage schedule

Hb monitoring

Monitor treatment

Iron status:not earlier

than 1 week after i.v. iron

routinely at intervals of between 4 weeks and 3 months

Haemoglobin: induction phase

of ESAs every 2–4 weeks

maintenance phase of ESAs every 1–3 months

more actively after ESA dose adjustment

Epoetin Alfa Darbepoetin Alfa

Indications

• Anemia of CKD • Chemotherapy induced anemia• HIV induced anemia• elective, noncardiac,nonvascular surgery

• Anemia of CKD • Chemotherapy induced anemia

Dosing Starting: 50 to 100 Units/kgTIW

Starting: 0.45 ug/kgInitial: 1 dose/week or.75mcg/kg qow

Target Hgb 10-12gm/dL Hgb 10-12gm/dL

Dose Response

2 to 6 weeks 2 to 6 weeks

Adapted from Package Inserts Data on File. Amgen, In; Thousand Oaks, CA

ESA Adverse EventsESA Adverse Events

Hypertension, or worsening of controlHypertension, or worsening of control Headache, arthralgias, nauseaHeadache, arthralgias, nausea Rarely: seizures, MI, stroke, antibody-Rarely: seizures, MI, stroke, antibody-

induced pure red cell aplasia (PRCA)induced pure red cell aplasia (PRCA) Adverse events from SQ Adverse events from SQ

administrationadministration StingingStinging Necrotic tissue lesionsNecrotic tissue lesions Subcutaneous nodulesSubcutaneous nodules

Hypo-responsiveness to Hypo-responsiveness to ESAsESAs

POTENTIAL CAUSESPOTENTIAL CAUSES1-41-4

Missed dosesMissed doses Inadequate iron storesInadequate iron stores

Iron deficiency is present in 25-37.5% of patients and is a Iron deficiency is present in 25-37.5% of patients and is a common cause of hyporesponsecommon cause of hyporesponse11

Drug/disease interactionsDrug/disease interactions Remember, iron needs an acidic environment to be Remember, iron needs an acidic environment to be

maximally absorbedmaximally absorbed BB12 12 or folate deficienciesor folate deficiencies Protein deficienciesProtein deficiencies Occult blood lossOccult blood loss Infection/inflammation processesInfection/inflammation processes Coexisting medical conditionsCoexisting medical conditions

Malignancies, hematological disordersMalignancies, hematological disorders HemolysisHemolysis

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 Monitoring Hgb “at regular intervals” once stabilizedHgb “at regular intervals” once stabilized1,21,2

CBC with differential and platelet count CBC with differential and platelet count regularlyregularly1,21,2

Blood pressure should be controlled Blood pressure should be controlled adequately before initiation of therapyadequately before initiation of therapy1,21,2

Fe studies (TSAT, ferritin) prior to and Fe studies (TSAT, ferritin) prior to and during therapyduring therapy1,21,2

Serum chemistry should be checked Serum chemistry should be checked regularly (BUN, creatinine, phosphorus, regularly (BUN, creatinine, phosphorus, uric acid, K+)uric acid, K+)11

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.

The Role of the Consultant The Role of the Consultant Pharmacist in the Pharmacist in the

Management of the Dialysis Management of the Dialysis PatientPatient CM 77yo male resident of short-stay facilityCM 77yo male resident of short-stay facility

Rehab s/p laminectomy; spinal stenosis, Rehab s/p laminectomy; spinal stenosis, gout, DM, HTN, CAD, COPD, RA, renal gout, DM, HTN, CAD, COPD, RA, renal failurefailure

Dialysis TIWDialysis TIW Weight Weight

Pre-dialysisPre-dialysis 79.6 kg79.6 kg Post-dialysisPost-dialysis 77.5 kg77.5 kg

Blood pressureBlood pressure Pre-dialysisPre-dialysis 192/76192/76 Post-dialysisPost-dialysis 163/74163/74

Additional InformationAdditional Information

Continuous oxygen at 2L/minContinuous oxygen at 2L/min Renal dietRenal diet Fluid restriction 1000cc qdFluid restriction 1000cc qd Labs:Labs:

Hgb 9.9 gm/dLHgb 9.9 gm/dL Glucose 86 mg/dLGlucose 86 mg/dL SCr 6.1; eGFR 10ml/minSCr 6.1; eGFR 10ml/min K+ 4.7 mEq/LK+ 4.7 mEq/L Calcium 9.1 mg/dLCalcium 9.1 mg/dL

Current MedicationsCurrent Medications Zyloprim 300mg qdZyloprim 300mg qd Colchicine .6mg qdColchicine .6mg qd Glipizide 10mg qdGlipizide 10mg qd Simvastatin 80mg qhsSimvastatin 80mg qhs Diovan 320mg bidDiovan 320mg bid Clonidine .1mg q12hClonidine .1mg q12h Hydralazine 50mg bidHydralazine 50mg bid Metoprolol 25mg bidMetoprolol 25mg bid

Furosemide 40mg Furosemide 40mg qdqd

Phos-Lo 667mg qd Phos-Lo 667mg qd w/mealw/meal

Nephrocaps qdNephrocaps qd Docusate 100mg Docusate 100mg

bidbid Chemsticks ac & hsChemsticks ac & hs Fosrenal 2000mg Fosrenal 2000mg

w/ each mealw/ each meal

What’s a What’s a Consultant to Consultant to

do???do???

The Role of the Consultant The Role of the Consultant Pharmacist in the Pharmacist in the

Management of the Dialysis Management of the Dialysis PatientPatient CM 77yo male resident of short-stay facilityCM 77yo male resident of short-stay facility

Rehab s/p laminectomy; spinal stenosis, Rehab s/p laminectomy; spinal stenosis, gout, DM, HTN, CAD, COPD, RA, renal gout, DM, HTN, CAD, COPD, RA, renal failurefailure

Dialysis TIWDialysis TIW Weight Weight

Pre-dialysisPre-dialysis 79.6 kg79.6 kg Post-dialysisPost-dialysis 77.5 kg77.5 kg

Blood pressureBlood pressure Pre-dialysisPre-dialysis 192/76192/76 Post-dialysisPost-dialysis 163/74163/74

Additional InformationAdditional Information

Continuous oxygen at 2L/minContinuous oxygen at 2L/min Renal dietRenal diet Fluid restriction 1000cc qdFluid restriction 1000cc qd Labs:Labs:

Hgb 9.9 gm/dLHgb 9.9 gm/dL Glucose 86 mg/dLGlucose 86 mg/dL SCr 6.1; eGFR 10ml/minSCr 6.1; eGFR 10ml/min K+ 4.7 mEq/LK+ 4.7 mEq/L Calcium 9.1 mg/dLCalcium 9.1 mg/dL

Current MedicationsCurrent Medications Zyloprim 300mg qdZyloprim 300mg qd Colchicine .6mg qdColchicine .6mg qd Glipizide 10mg qdGlipizide 10mg qd Simvastatin 80mg qhsSimvastatin 80mg qhs Diovan 320mg bidDiovan 320mg bid Clonidine .1mg q12hClonidine .1mg q12h Hydralazine 50mg bidHydralazine 50mg bid Metoprolol 25mg bidMetoprolol 25mg bid

Furosemide 40mg Furosemide 40mg qdqd

Phos-Lo 667mg qd Phos-Lo 667mg qd w/mealw/meal

Nephrocaps qdNephrocaps qd Docusate 100mg Docusate 100mg

bidbid Chemsticks ac & hsChemsticks ac & hs Fosrenal 2000mg Fosrenal 2000mg

w/ each mealw/ each meal

Case StudiesCase Studies

The Role of the Consultant The Role of the Consultant Pharmacist in the Pharmacist in the Management ofManagement of

Anemia of CKDAnemia of CKD

Case 1Case 1

RB is an 85yo male resident of a LTCFRB is an 85yo male resident of a LTCF Two months ago he was started on Two months ago he was started on

ferrous sulfate 325mg bid for “anemia”ferrous sulfate 325mg bid for “anemia” Follow-up labsFollow-up labs

Hgb 8.1 g/dl Hgb 8.1 g/dl Hct 32%Hct 32% Iron 45 mcg/dlIron 45 mcg/dl

Recent hospital return on epoetin alfa Recent hospital return on epoetin alfa 30,000 units TIW (wt 75kg)30,000 units TIW (wt 75kg)

Case 1 cont’dCase 1 cont’d

CP recommends labCP recommends lab Hgb 8.9 g/dlHgb 8.9 g/dl Hct 35%Hct 35% TSAT 18%TSAT 18% Ferritin 92 ng/mlFerritin 92 ng/ml

Hgb has not increased significantly Hgb has not increased significantly over 4 weeksover 4 weeks TSAT should be >= 20%TSAT should be >= 20% Ferritin >= 100ng/mlFerritin >= 100ng/ml

Case 1 cont’dCase 1 cont’d

Consider possible causes for lack of Consider possible causes for lack of rise in Hgbrise in Hgb Appropriate dosing?Appropriate dosing?

30,000 units TIW for 75 kg patient; the 30,000 units TIW for 75 kg patient; the recommended starting dose for epo is 50-recommended starting dose for epo is 50-100 units/kg TIW, IV or SC100 units/kg TIW, IV or SC

The starting dose range based on weight The starting dose range based on weight would be 37,500 – 75,000 units TIWwould be 37,500 – 75,000 units TIW

If Hgb does not increase by 1g/dl after 4 If Hgb does not increase by 1g/dl after 4 weeks weeks andand iron stores are adequate, iron stores are adequate, increase dose by 25%increase dose by 25%

Case 1 cont’dCase 1 cont’d

Are iron stores adequate in this resident?Are iron stores adequate in this resident? No, based on reported labsNo, based on reported labs

CP discusses administration of iron with CP discusses administration of iron with nursesnurses

PRN antacid is frequently given with the iron PRN antacid is frequently given with the iron to reduce c/o of GI upset; or, doses are heldto reduce c/o of GI upset; or, doses are held

For optimal absorption, iron should be given For optimal absorption, iron should be given 1 hr before or 2 hrs after meals, but may be 1 hr before or 2 hrs after meals, but may be given with food to reduce GI irritationgiven with food to reduce GI irritation

Case 1 cont’dCase 1 cont’d

What action should be taken by the CP?What action should be taken by the CP? Educate staff on proper administration of ironEducate staff on proper administration of iron Recommend to prescriber to increase epo dose to Recommend to prescriber to increase epo dose to

40,000 units TIW40,000 units TIW Check iron, ferritin, TSAT in about a monthCheck iron, ferritin, TSAT in about a month Hgb should be checked at least weekly x 4 after a Hgb should be checked at least weekly x 4 after a

dosage change (then monthly, when stabilized)dosage change (then monthly, when stabilized) Clinically significant improvements may not Clinically significant improvements may not

be seen for 2-6 weeks, but do not adjust dose be seen for 2-6 weeks, but do not adjust dose any more frequently than once per monthany more frequently than once per month

Case 2Case 2

JC is an 80yo female resident of a JC is an 80yo female resident of a LTCFLTCF

Primary Dx: HTN, anemia of CKDPrimary Dx: HTN, anemia of CKD Hgb 8.7 g/dlHgb 8.7 g/dl Taking 45,000 units erythropoietin Taking 45,000 units erythropoietin

TIW x 4 weeks, Hgb results:TIW x 4 weeks, Hgb results: Week 1Week 1 9.1 g/dl9.1 g/dl Week 2Week 2 10.1 g/dl10.1 g/dl Week 3Week 3 11.9 g/dl11.9 g/dl

Case 2Case 2

If there is a rapid increase in Hgb If there is a rapid increase in Hgb (>1g/dl in any 2 week period) (>1g/dl in any 2 week period) OROR

The Hgb is increasing and The Hgb is increasing and approaching 12approaching 12

Reduce weekly dose by approximately Reduce weekly dose by approximately 25%25%

Rapid rise increases risk of Rapid rise increases risk of exacerbation of HTNexacerbation of HTN

ESAs should not be used in patients ESAs should not be used in patients with with uncontrolleduncontrolled HTN HTN