Anemia Indian scenario In Chronic Kidney Disease Patients

Anaemia management IndianAnaemia management Indian
ScenaroScenaro
Presented by-Dr(Lt Col) Ashutosh
Ojha, MD
PDCDM Student
GMCH,Guwahati-32
Moderator-Prof AK Barman
Prof & HoD(Nephrology)

Estimates of prevalence of CKD inEstimates of prevalence of CKD in
the USA: NHANES IIIthe USA: NHANES III
StageStage DescriptionDescription
GFRGFR
(ml/min/1.73(ml/min/1.73
mm22
))
PrevalencePrevalence
(%)(%)
11
Kidney damage withKidney damage with
normal ornormal or ↑↑ GFRGFR
>>9090 3.33.3
22
Kidney damage withKidney damage with
mildmild ↓↓ GFRGFR
60–8960–89 3.03.0
33 ModerateModerate ↓↓ GFRGFR 30–5930–59 44.3.3
44 SevereSevere ↓↓ GFRGFR 15–2915–29 0.20.2
55 Kidney failureKidney failure <<15 or15 or
(or d(or dialysisialysis))
0.10.1
Coresh et al AJKD 2003

EXTENT OF CKD IN INDIAEXTENT OF CKD IN INDIA
India-diabetic capital. Every 5India-diabetic capital. Every 5thth
Indian diabetic andIndian diabetic and
every 5every 5thth
Indian HypertensiveIndian Hypertensive
40-50% of all chronic kidney disease is due to40-50% of all chronic kidney disease is due to
diabetesdiabetes
Prevalence of CKDPrevalence of CKD
Chennai- 0.16Chennai- 0.16
Delhi- 0.78Delhi- 0.78
Incidence of CKDIncidence of CKD 
151-232 per million population151-232 per million population (Jha et al)(Jha et al)
785 per million population785 per million population (Agarwal et al)(Agarwal et al)

Cause of End Stage Renal DiseaseCause of End Stage Renal Disease
(SJMCH)(SJMCH)
10%
40%
28%
18%
4%
Diabetics
htn
IN
Others
Unknown

Challenges in Anaemia ManagementChallenges in Anaemia Management
Many patients affected by anaemiaMany patients affected by anaemia
0
5
10
15
20
25
30
35
40
45
50
> 90 60-89 30-59 15-29
Astor et al 2002n=15 625
Patients (%)
GFR (mL/min per 1.73 m2
)
44

CORRECTION OF ANEMIACORRECTION OF ANEMIA
TARGET HAEMOGLOBIN =11-12 grams/dl

CKD AnaemiaCKD Anaemia
Correlates with SurvivalCorrelates with Survival
Survival of CKD Patients by Haemoglobin Level
Reproduced courtesy of A Levin
CKD Anaemia
Correlates With Survival
Time (months)
ProbabilityofSurvival
0 3 6 9 12 15 18 21 24 27 30 33 36
0.70
0.75
0.80
0.85
0.90
0.95
1.00
Baseline
haemoglobin
Log-Rank Test: p = 0.0001
=
12 - 13 g/dL
11-12 g/dL
10-11 g/dL
10 g/dL
13 g/dL
<
Survival of CKD Patients by Haemoglobin Level
Reproduced courtesy of A Levi

Association between renal anaemia andAssociation between renal anaemia and
relative risk of death or hospitalisationrelative risk of death or hospitalisation
Locatelli et al NDT 2004
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
<10 10–10.9 11–11.9 ≥12
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
<10 10–10.9 11–11.9 ≥12
Relative risk of death Relative risk of hospitalisation
RR, overall=0.95 per
1 g/dl higher Hb (p=0.03)
RR, overall=0.96 per
1 g/dl higher Hb (p=0.02)
1.22
1.02 1
0.91
1.29
1.09
1
1.07
p=0.06 p=0.86 Ref p=0.49 p<0.001 p=0.14 Ref p=0.44
(n) (1626) (952) (760) (682) (1521) (919) (733) (670)
RR
Hb (g/dl) at study entry
RR
Target of 10-12 g/dl is appropriate
Renal Anemia correlates with outcome

Problems in anemia management inProblems in anemia management in
CKDCKD
Common challenges faced are –Common challenges faced are –
– Maintenance of stable hemoglobin levels in theirMaintenance of stable hemoglobin levels in their
patientspatients
– Avoid overshooting Hb targetsAvoid overshooting Hb targets
– Balance intravenous iron & EPOBalance intravenous iron & EPO
– Improve EPO response to use the lowest effectiveImprove EPO response to use the lowest effective
EPO doseEPO dose
A major concern is EPO hyporesponsiveness &A major concern is EPO hyporesponsiveness &
insufficient iron replacementinsufficient iron replacement
IV iron is important in managing theseIV iron is important in managing these
challenges to a large extentchallenges to a large extent
Kapoian T. Challenge of effectively using erythropoiesis-stimulating agents
and intravenous iron. Am J Kidney Dis. 2008 Dec;52(6 Suppl):S21-8.

Worldwide prevalence and incidenceWorldwide prevalence and incidence
of CKDof CKD
More than 1.7 million treated with renalMore than 1.7 million treated with renal
replacement therapy worldwide in 2004replacement therapy worldwide in 2004
90% patients receiving RRT live in industrialized90% patients receiving RRT live in industrialized
countriescountries
The incidence of CKD requiring renal replacementThe incidence of CKD requiring renal replacement
therapy has doubled over the last 15 yearstherapy has doubled over the last 15 years
Dramatically increasing prevalence predicted in the nextDramatically increasing prevalence predicted in the next
10 years largely due to the aging population and10 years largely due to the aging population and
increasing incidence of type 2 diabetesincreasing incidence of type 2 diabetes
El Nahas & Bello 2005
Grassmann et al 2005

0
100
200
300
400
500
78 80 82 84 86 88 90 92 94 96 98 00 02
CKD incidence and prevalenceCKD incidence and prevalence
increasingincreasing
Prevalent dialysis
and transplant
(2002: 431 284)
Prevalent dialysis
(2002: 308 910)
Prevalent transplant
(2002: 122 374)
Incident dialysis
and transplant
(2002: 100 359)
Year
No. of patients (thousands)
USRDS 2004 Annual Data Report

Undertreatment of anaemia remainsUndertreatment of anaemia remains
Locatelli et al 2004
Pisoni et al 2004
Mean Hb (g/dL)
6
7
8
9
10
11
12
13
Sw
eden
U
SA
Spain
B
elgium
C
anada
Australia
/N
Z
G
erm
any
Italy
U
K
France
Japan
Prevalent
Incident

Many patients below Hb targetMany patients below Hb target
Locatelli et al 2004
Pisoni et al 2004
(%) Patients with Hb <11 g/dL
0 10 20 30 40 50 60 70 80 90 100
Sweden
USA
Spain
Belgium
Canada
Australia / NZ
Germany
Italy
UK
France
Japan
Prevalent
Incident

USRDS Kaplan-Meier estimates of the probability of death or
a first non-fatal myocardial infarction in the normal-
hematocrit groups

Mark A. Parazella,MD. CKD series: evaluation and treatment of anemia in chronic kidney
disease. Hospital physician. 2003; 31-38,46

INDIAN BEST PRACTICEINDIAN BEST PRACTICE
GUIDELINESGUIDELINES

Anaemia in CRF can be due to multipleAnaemia in CRF can be due to multiple
causes, most commonly EPO deficiencycauses, most commonly EPO deficiency
and nutritional factors. Since EPO isand nutritional factors. Since EPO is
expensive, all efforts must be made toexpensive, all efforts must be made to
correct nutritional deficiencies especiallycorrect nutritional deficiencies especially
iron deficiency and assessment of otheriron deficiency and assessment of other
nutritional factorsnutritional factors..
Indian Best Practices GuidelinesIndian Best Practices Guidelines

Guideline 1: Anaemia EvaluationGuideline 1: Anaemia Evaluation
(Evidence level A)(Evidence level A)
 RBC indices / Peripheral smearRBC indices / Peripheral smear
 Iron / TIBC / Ferritin / TranferrinIron / TIBC / Ferritin / Tranferrin
saturationsaturation
 Stool occult bloodStool occult blood
 Stool parasite testStool parasite test
 Serum B12 & Red cell folateSerum B12 & Red cell folate
concentrationsconcentrations

Guideline 1 (a): Anaemia EvaluationGuideline 1 (a): Anaemia Evaluation
 RBC indices / Peripheral smearRBC indices / Peripheral smear
 Iron / TIBC / Ferritin / TranferrinIron / TIBC / Ferritin / Tranferrin
saturationsaturation
 Stool occult bloodStool occult blood
 Stool parasite testStool parasite test
A fuller work up should also include theA fuller work up should also include the
followingfollowing
as indicated.as indicated.
 Serum B12 and red cell folateSerum B12 and red cell folate
concentrationsconcentrations

Guideline 1 (a): Anaemia EvaluationGuideline 1 (a): Anaemia Evaluation
(contd..)(contd..)
 Serum and / or urine protein electrophoresis /Serum and / or urine protein electrophoresis /
immunoblottingimmunoblotting
(where available).(where available).
 Serum aluminiumSerum aluminium
 Bone marrow examination in selected casesBone marrow examination in selected cases
 Assessment of occult gastrointestinal blood loss.Assessment of occult gastrointestinal blood loss.
Elements of this work up will be necessary if there isElements of this work up will be necessary if there is
clinical suspicion of primary haematological disorderclinical suspicion of primary haematological disorder
(haemolysis, marrow dysplasia), macrocytosis,(haemolysis, marrow dysplasia), macrocytosis,
aluminium poisoning or occult blood loss).aluminium poisoning or occult blood loss).
(Evidence level A)

Guideline 2(a): Diagnosis of AnaemiaGuideline 2(a): Diagnosis of Anaemia
of Chronic Renal Failureof Chronic Renal Failure
 No cause other than CRF by aboveNo cause other than CRF by above
investigation.investigation.
 GFR <30 in non-diabetics and 45ml/min. inGFR <30 in non-diabetics and 45ml/min. in
diabetic patients (S. creat >2mg/dl).diabetic patients (S. creat >2mg/dl).
 Measurement of plasma EPO concentrationMeasurement of plasma EPO concentration
notnot indicated.indicated.

Guideline 7: What are the causesGuideline 7: What are the causes
of inadequate response to EPOof inadequate response to EPO
(contd..)(contd..)
vi)vi) HemolysisHemolysis
VVii)ii) Osteitis fibrosaOsteitis fibrosa
viii)viii) Aluminium toxicityAluminium toxicity
ix)ix) Haemoglobinopathies (e.g. alpha & BetaHaemoglobinopathies (e.g. alpha & Beta
thalassemias, sickle cell anaemia)thalassemias, sickle cell anaemia)
x)x) Multiple myeloma & other malignancies.Multiple myeloma & other malignancies.
xi)xi) Use of ACE-1 / ARB agentsUse of ACE-1 / ARB agents

Guideline 7(a): Resistance to EPO /Guideline 7(a): Resistance to EPO /
inadequate response to EPOinadequate response to EPO
 Failure to achieve target Hb concentrationFailure to achieve target Hb concentration
a)a) While receiving more than 300IU/kg/week S.C orWhile receiving more than 300IU/kg/week S.C or
450units IU/kg/week IV.450units IU/kg/week IV.
b) Continued need for such dosage to maintain targetb) Continued need for such dosage to maintain target
in presence of adequate iron stores.in presence of adequate iron stores.
 Resistance (hypo responsiveness) is relativeResistance (hypo responsiveness) is relative
 In the absence of detectable abnormalities of any oneIn the absence of detectable abnormalities of any one
of the above conditions – marrow examination isof the above conditions – marrow examination is
indicated (for diagnosis of resistance) includingindicated (for diagnosis of resistance) including
haematologist reference.haematologist reference.

Need for IV iron in CKDNeed for IV iron in CKD
Iron deficiency in CKD patients develops primarily duringIron deficiency in CKD patients develops primarily during
the correction of renal anemia by EPO treatmentthe correction of renal anemia by EPO treatment
Among ESRD patients receiving EPO,Among ESRD patients receiving EPO, more than 50%more than 50%
are iron deficientare iron deficient
Approximately 150 mg of iron is necessary for anApproximately 150 mg of iron is necessary for an
increase of 1 g/dl in hemoglobin levelincrease of 1 g/dl in hemoglobin level
Causes of anemia in CKD patients include –Causes of anemia in CKD patients include –
– Inadequate intake of dietary ironInadequate intake of dietary iron
– Blood loss during the extracorporeal procedure GI bleedingBlood loss during the extracorporeal procedure GI bleeding
– Inadequate intestinal iron absorption and inhibition of iron releaseInadequate intestinal iron absorption and inhibition of iron release
from macrophagesfrom macrophages
– Increased iron requirements during therapy withIncreased iron requirements during therapy with erythropoiesis-erythropoiesis-
stimulating agents (ESAs).stimulating agents (ESAs).
1. Horl WH. Iron therapy for renal anemia: how much needed, how much harmful?
Pediatr Nephrol 2007;22:480–9.
2. Guidelines for anemia of chronic kidney disease. NKF K/DOQI guidelines 2000. Available at:
http://www.kidney.org/PROFESSIONALS/kdoqi/guidelines_updates/doqiupan_iii.html#5

IV iron in CKDIV iron in CKD
IV iron therapy is superior to oral ironIV iron therapy is superior to oral iron
supplementation in CKDsupplementation in CKD
Risk factors associated with IV iron therapyRisk factors associated with IV iron therapy
acute allergic reactionsacute allergic reactions
long-termlong-term
complications caused by thecomplications caused by the generation ofgeneration of
powerful oxidant species,powerful oxidant species, Allergy is to related toAllergy is to related to
dextran moietydextran moiety
Iron dextran is associated with higher incidenceIron dextran is associated with higher incidence
of Type I hypersensitivity than Iron sucroseof Type I hypersensitivity than Iron sucrose
Iron sucrose carries the lowest risk forIron sucrose carries the lowest risk for
hypersensitivityhypersensitivity
1. Horl WH. Iron therapy for renal anemia: how much needed, how much harmful? Pediatr Nephrol
2007;22:480–9.

Iron sucrose in kidney diseaseIron sucrose in kidney disease
Iron deficiency may be corrected by oral ironIron deficiency may be corrected by oral iron
supplementation but it is limited by –supplementation but it is limited by –
– Poor compliancePoor compliance
– Adverse gastrointestinal reactionsAdverse gastrointestinal reactions
IV iron preparations commonly used includeIV iron preparations commonly used include
iron sucrose, sodium ferric gluconate, & ironiron sucrose, sodium ferric gluconate, & iron
dextrandextran
Iron sucrose is safer than iron dextran, isIron sucrose is safer than iron dextran, is
generally considered a safe and effective IVgenerally considered a safe and effective IV
iron preparation in renal anemiairon preparation in renal anemia
1. Li H. Intravenous iron sucrose in peritoneal dialysis patients with renal
anemia. Peritoneal Dialysis International 2008;28:149–54.

Iron sucrose in kidney diseaseIron sucrose in kidney disease
Iron sucrose is a novel and effective addition inIron sucrose is a novel and effective addition in
the management of ‘Anemia related to kidneythe management of ‘Anemia related to kidney
diseases’diseases’
Iron Sucrose is elemental iron whichIron Sucrose is elemental iron which
replenishes body iron stores in patients withreplenishes body iron stores in patients with
iron deficiencyiron deficiency
Approximately 25% of hemodialysis patientsApproximately 25% of hemodialysis patients
can be maintained on oral ironcan be maintained on oral iron
supplementation; the others require IV ironsupplementation; the others require IV iron
supplementationsupplementation
1. Dennis J. Cada. Iron Sucrose Injection. Drug Reviews From The Formulary, Volume 36, April 2001,404-412
2. W.H. Horl, OPTA-therapy with iron and erythropoiesis-stimulating agents in chronic kidney disease, nephrology dial transplant. 2007 suppl 3;iii2-iii6

IndicationsIndications
IV iron sucrose is indicated in –IV iron sucrose is indicated in –
– Non-Dialysis Dependent - Chronic Kidney Disease (NDD-Non-Dialysis Dependent - Chronic Kidney Disease (NDD-
CKD) patients receiving an erythropoietinCKD) patients receiving an erythropoietin
– Non-Dialysis Dependent - Chronic Kidney Disease (NDD-Non-Dialysis Dependent - Chronic Kidney Disease (NDD-
CKD) patients not receiving an erythropoietinCKD) patients not receiving an erythropoietin
– Hemodialysis Dependent - Chronic Kidney Disease (HDD-Hemodialysis Dependent - Chronic Kidney Disease (HDD-
CKD) patients receiving an erythropoietinCKD) patients receiving an erythropoietin
– Peritoneal Dialysis Dependent - Chronic Kidney DiseasePeritoneal Dialysis Dependent - Chronic Kidney Disease
(PDD-CKD) patients receiving an erythropoietin(PDD-CKD) patients receiving an erythropoietin
1. Venofer® [package insert]. Shirley, NY: American Regent, Inc.; 2007.
2. Hollands JM et al. Safety of High-Dose Iron Sucrose Infusion in Hospitalized Patients With Chronic Kidney Disease. Am J Health-Syst Pharm. 2006;63(8):731-734.
3. Mircescu G et al. Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients. Nephrol Dial Transplant 2006;21:120-4.

Iron sucrose in pre-dialysis CRFIron sucrose in pre-dialysis CRF
patientspatients
Patients undergoing chronicPatients undergoing chronic
hemodialysis often present with anemiahemodialysis often present with anemia
IV iron therapy is administered inIV iron therapy is administered in
conjunction with EPO as it helps preventconjunction with EPO as it helps prevent
EPO-hypo-responsivenessEPO-hypo-responsiveness
Study evaluated use of Iron sucrose inStudy evaluated use of Iron sucrose in
pre dialyzed patients of CRFpre dialyzed patients of CRF
60 non-diabetic CRF patients were60 non-diabetic CRF patients were
included in the studyincluded in the study
Mircescu G ,et al. Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients. Nephrol Dial
Transplant 2006;21:120-4.

ResultsResults
60 patients included in the study60 patients included in the study
58% of patients reporting a rise in Hb > 1 g/dL vs. baseline in the study58% of patients reporting a rise in Hb > 1 g/dL vs. baseline in the study
80% of patients had a Hb > 10 g/dL vs. 44% at baseline80% of patients had a Hb > 10 g/dL vs. 44% at baseline
55% had a Hb > 11 g/dL vs. 0% at baseline55% had a Hb > 11 g/dL vs. 0% at baseline
Mean serum iron concentration increased from –Mean serum iron concentration increased from –
– 73.973.9 µµg/dL at baselineg/dL at baseline
– 84.284.2 µµg/dL at 6 monthsg/dL at 6 months
– 101.8101.8 µµg/dL at 12 months of therapyg/dL at 12 months of therapy
No worsening of renal function, and no adverse events were reportedNo worsening of renal function, and no adverse events were reported
Mircescu G et al. Intravenous iron supplementation for the treatment of anaemia in pre-
dialyzed chronic renal failure patients. Nephrol Dial Transplant 2006;21:120-4.
Serum Iron concentration
Baseline 6 months 12 months
0
10
20
30
40
50
60
70
80
90
100
110
Mean Serum Fe concentration
Time line
MeanserumFeConc.

Efficacy of Iron sucrose inEfficacy of Iron sucrose in
hemodialysis patientshemodialysis patients
Schiesser et al conducted a prospectiveSchiesser et al conducted a prospective
multicentre clinical trial in 50 iron-multicentre clinical trial in 50 iron-
replete hemodialysis patients toreplete hemodialysis patients to
evaluate the efficacy of iron sucroseevaluate the efficacy of iron sucrose
administration for 6 monthsadministration for 6 months
Hb level remained stable (12Hb level remained stable (12±±1.1 at1.1 at
baseline & 12.1baseline & 12.1±±1.5 g/dl at the end of1.5 g/dl at the end of
the study)the study)
Reduced dose for EPOReduced dose for EPO
Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-
replete haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–5.

Iron sucrose IV reduces EPOIron sucrose IV reduces EPO
demand in dialysis patientsdemand in dialysis patients
In the study of Iron sucrose inIn the study of Iron sucrose in
hemodialysis patients conducted byhemodialysis patients conducted by
Schiesser et al the dosage for the threeSchiesser et al the dosage for the three
different epoetins decreased by –different epoetins decreased by –
– 38.5% with darbepoetin alfa38.5% with darbepoetin alfa
– 6.3% with epoetin alfa6.3% with epoetin alfa
– 8.3% with epoetin beta8.3% with epoetin beta
Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement
in iron-replete haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–5.

Results showing reduced EPOResults showing reduced EPO
need with iron sucroseneed with iron sucrose
Schiesser et al showed reduced EPOSchiesser et al showed reduced EPO
need with low dose maintenance ironneed with low dose maintenance iron
sucrose in their studysucrose in their study
Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete
haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–5.

IV iron reduces EPO demand inIV iron reduces EPO demand in
dialysis patientsdialysis patients
Chang et al studies the beneficial effects of 2Chang et al studies the beneficial effects of 2
weekly IV iron supplementation compared to onceweekly IV iron supplementation compared to once
monthly IV iron in 149 iron replete patientsmonthly IV iron in 149 iron replete patients
EPO requirementEPO requirement reduced by 25%reduced by 25% when sereumwhen sereum
ferritin & Transferrin saturation was maintained atferritin & Transferrin saturation was maintained at
high levels by administering 2 weekly IV ironhigh levels by administering 2 weekly IV iron
compared to IV iron given once monthlycompared to IV iron given once monthly
Significant decrease in serum albumin, cholesterolSignificant decrease in serum albumin, cholesterol
& pre-dialysis creatinine when IV iron was& pre-dialysis creatinine when IV iron was
administered 2 weekly for 1 yearadministered 2 weekly for 1 year
Chang CH et al. Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in
iron-replete hemodialysis patients. Clin Nephrol. 2002;57:136-41.

IV iron reduces EPO demand in dialysisIV iron reduces EPO demand in dialysis
patients – Results from Meta analysispatients – Results from Meta analysis
Compared to oral iron IV iron preparations significantlyCompared to oral iron IV iron preparations significantly
reduce the EPO requirement in dialysis patientsreduce the EPO requirement in dialysis patients
Rozen-Zvi et al. Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: Systematic Review and Meta-analysis. American Journal of Kidney Diseases
2008;52:897-906.

Iron sucrose in CKD patients not onIron sucrose in CKD patients not on
dialysisdialysis
Charytan et al compared oral iron withCharytan et al compared oral iron with
Iron sucrose in 96 NDD-CKD patientsIron sucrose in 96 NDD-CKD patients
More IV iron patients (54.2%) attainedMore IV iron patients (54.2%) attained
hemoglobin values > 11.0 g/dlhemoglobin values > 11.0 g/dl
compared to oral iron patients (31.3%)compared to oral iron patients (31.3%)
There were no serious side effects withThere were no serious side effects with
iron sucroseiron sucrose
Charytan C et al. Comparison of intravenous iron sucrose to oral iron in the treatment of anemic patients with chronic kidney
disease not on dialysis. Nephron Clin Pract. 2005;100(3):c55-62.

Efficacy & safety of Iron sucrose inEfficacy & safety of Iron sucrose in
peritoneal dialysis patientsperitoneal dialysis patients
Li et al conducted a study to compare the clinicalLi et al conducted a study to compare the clinical
outcomes & safety of IV iron sucrose & oral ferrousoutcomes & safety of IV iron sucrose & oral ferrous
succinate in combination with rHuEPO therapy insuccinate in combination with rHuEPO therapy in
patients on maintenance PDpatients on maintenance PD
46 patients were included – 26 received iron sucrose &46 patients were included – 26 received iron sucrose &
20 oral20 oral ironiron
Hb & Hct increased significantly at 2 weeks in the IVHb & Hct increased significantly at 2 weeks in the IV
group compared with baselinegroup compared with baseline
The total response rate at 8 weeks was 94.8% for the IVThe total response rate at 8 weeks was 94.8% for the IV
group - significantly higher than that of the oral groupgroup - significantly higher than that of the oral group
(55.0%)(55.0%)
There were no adverse events with IV ironThere were no adverse events with IV iron
8 patients in the oral group had adverse GI effects8 patients in the oral group had adverse GI effects
Li H. Intravenous iron sucrose in peritoneal dialysis patients with renal anemia. Peritoneal Dialysis International 2008;28:149–54.

Results of Iron sucrose in PDResults of Iron sucrose in PD
patients contd.patients contd.
Response rates to IV iron sucroseResponse rates to IV iron sucrose
therapy compared to Oral iron therapytherapy compared to Oral iron therapy
Li H. Intravenous iron sucrose in peritoneal dialysis patients with renal anemia. Peritoneal Dialysis International 2008;28:149–54.

Efficacy of Iron sucrose in ESRDEfficacy of Iron sucrose in ESRD
Iron sucrose in apparently iron-repleteIron sucrose in apparently iron-replete
patients will decrease the EPOpatients will decrease the EPO
requirements for a given targetrequirements for a given target
hematocrit in patients on maintenancehematocrit in patients on maintenance
hemodialysis with end-stage renalhemodialysis with end-stage renal
disease (ESRD)disease (ESRD)
1. Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin
requirement in iron-replete haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–2845.
2. Shaldon S. The use of IV iron in the treatment of anaemia of ESRD patients on maintenance haemodialysis: an historical and
personal view. Nephrol Dial Transplant (2007) 22: 23–25.

Safety of Iron sucroseSafety of Iron sucrose
Aronoff et al studied the safety of ironAronoff et al studied the safety of iron
sucrose in hemodialysis patientssucrose in hemodialysis patients
665 hemodialysis patients with 80 who665 hemodialysis patients with 80 who
had experienced previous intolerance tohad experienced previous intolerance to
other IV iron preparations were given ironother IV iron preparations were given iron
sucrosesucrose
There were no serious or life-threateningThere were no serious or life-threatening
drug-related adverse eventsdrug-related adverse events
Aronoff GR et al. Iron sucrose in hemodialysis patients: Safety of replacement and maintenance regimens. Kidney International,
2004;66:1193–8.

Iron sucrose in patientsIron sucrose in patients
hypersensitive to iron dextranhypersensitive to iron dextran
Iron dextran has been the onlyIron dextran has been the only
available parenteral ironavailable parenteral iron
preparation for a long timepreparation for a long time
Its use has been associated withIts use has been associated with
increased risk of allergic reactions,increased risk of allergic reactions,
even after reaction-free previouseven after reaction-free previous
useuse
Haddad A et al. Use of Iron Sucrose in Dialysis Patients Sensitive to Iron Dextran. Saudi J Kidney Dis Transpl 2009;20(2):208-211

Safety of Iron sucrose comparedSafety of Iron sucrose compared
to other iron preparationsto other iron preparations
Rates of life-threatening ADEs –Rates of life-threatening ADEs –
1.1. 0.6 per million for iron0.6 per million for iron
sucrosesucrose
2.2. 0.9 per million for sodium0.9 per million for sodium
ferric gluconate complexferric gluconate complex
3.3. 3.3 per million for lower3.3 per million for lower
molecular weight iron dextranmolecular weight iron dextran
4.4. 11.3 per million per million for11.3 per million per million for
higher molecular weight ironhigher molecular weight iron
dextrandextran
Chertow GM et al. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant (2006) 21: 378–382.
Safety of Iron preparations
1 2 3 4
0
1
2
3
4
5
6
7
8
9
10
11
12
Iron preparations
ADEpermillion

Dosing and administrationDosing and administration
NDD-CKD - ANDD-CKD - Administered as a total cumulativedministered as a total cumulative
dose of 1,000 mg over a 14 days as a 200 mgdose of 1,000 mg over a 14 days as a 200 mg
slow IV injection undiluted over 2 to 5 minutesslow IV injection undiluted over 2 to 5 minutes
on 5 different occasions.on 5 different occasions.
HDD-CKD - AHDD-CKD - Administered undiluted as a 100dministered undiluted as a 100
mg slow IV over 2 to 5 minutes or as anmg slow IV over 2 to 5 minutes or as an
infusion of 100 mg, diluted in a maximum of 100infusion of 100 mg, diluted in a maximum of 100
mL of NS over 15 minutes per consecutivemL of NS over 15 minutes per consecutive
hemodialysis session for a total cumulativehemodialysis session for a total cumulative
dose of 1,000 mg.dose of 1,000 mg.

Dosing and administration contd.Dosing and administration contd.
PDD-CKD - APDD-CKD - Administered undiluted as a totaldministered undiluted as a total
cumulative dose of 1,000 mg in 3 divided doses,cumulative dose of 1,000 mg in 3 divided doses,
given by slow IV infusion, over 28 days:given by slow IV infusion, over 28 days:
– 2 infusions of 300 mg over 1.5 hs 14 days apart2 infusions of 300 mg over 1.5 hs 14 days apart
– Followed by 1 400 mg infusion over 2.5 h 14 days laterFollowed by 1 400 mg infusion over 2.5 h 14 days later
– Should be diluted in 250 mL of NSShould be diluted in 250 mL of NS
Low maintenance doses in hemodialysisLow maintenance doses in hemodialysis
patients include 50mg injected into the venouspatients include 50mg injected into the venous
limb of the haemodialysis tubing system (slowlimb of the haemodialysis tubing system (slow
intravenous push at a rate of 10 mg/min)intravenous push at a rate of 10 mg/min)

Dosing and administration contd.Dosing and administration contd.
The usual dose is 100 mg administered one toThe usual dose is 100 mg administered one to
three times per week.three times per week.
Most patients will require a minimumMost patients will require a minimum
cumulative dose of 1000 mg of elemental ironcumulative dose of 1000 mg of elemental iron
administered over 10 sequential dialysisadministered over 10 sequential dialysis
sessions to achieve a favorable responsesessions to achieve a favorable response
Patients may continue to receive IV ironPatients may continue to receive IV iron
therapy at the lowest dose necessary totherapy at the lowest dose necessary to
maintain target levels of hemoglobin,maintain target levels of hemoglobin,
hematocrit & iron storage parametershematocrit & iron storage parameters
Cada DJ. Iron Sucrose Injection. Hospital Pharmacy 2001;36:404–12.

Monitoring parametersMonitoring parameters
Patients receiving regular IV iron therapy requirePatients receiving regular IV iron therapy require
monitoring of hematologic parameters & iron indices (Hb,monitoring of hematologic parameters & iron indices (Hb,
Hct, TSAT, & ferritin)Hct, TSAT, & ferritin)
Maintain TSAT between 20% and 50%Maintain TSAT between 20% and 50%
Iron therapy should be withheld in patients with TSATIron therapy should be withheld in patients with TSAT
≥50%≥50%
Iron therapy should be withheld in patients with ferritinIron therapy should be withheld in patients with ferritin
values ≥800 ng/mLvalues ≥800 ng/mL
Since transferrin saturation values increase rapidly afterSince transferrin saturation values increase rapidly after
IV administration of iron sucrose, serum iron values mayIV administration of iron sucrose, serum iron values may
be reliably obtained 48 hours after IV iron sucrose dosingbe reliably obtained 48 hours after IV iron sucrose dosing
Cada DJ. Iron Sucrose Injection. Hospital Pharmacy 2001;36:404–12.

INDIAN BEST PRACTICEINDIAN BEST PRACTICE
GUIDELINES … contdGUIDELINES … contd

Guideline 9: When to assess ironGuideline 9: When to assess iron
status after EPO therapystatus after EPO therapy
1)1) Iron status must be assessed once in 3Iron status must be assessed once in 3
months while on EPO therapy.months while on EPO therapy.

Guideline 9(a): When to assessGuideline 9(a): When to assess
iron status after EPO therapy?iron status after EPO therapy?
 CKD patients should have sufficientCKD patients should have sufficient
iron stores to maintain target Hb%iron stores to maintain target Hb%
(Evidence).(Evidence).
 To achieve this, sufficient iron to beTo achieve this, sufficient iron to be
administered.administered.
to maintain TSAT>20%to maintain TSAT>20%
Ferritin >100ng/mlFerritin >100ng/ml

Guideline 9(a): When to assess ironGuideline 9(a): When to assess iron
status after EPO therapy?status after EPO therapy?
(contd..)(contd..)
 To achieve this level, aim atTo achieve this level, aim at
- TSAT 30-40%- TSAT 30-40%
- Ferritin 200-500ng/ml- Ferritin 200-500ng/ml
(Evidence level B)(Evidence level B)
 No benefit is achieved if TSAT >50% & serumNo benefit is achieved if TSAT >50% & serum
ferritin >800ng/ml and iron should not beferritin >800ng/ml and iron should not be
administered beyond this level (Evidence B)administered beyond this level (Evidence B)

Monitoring iron stores &Monitoring iron stores &
supplement Ironsupplement Iron
1.1. During initiation of EPO & increased doseDuring initiation of EPO & increased dose
of EPO.of EPO.
TSAT / serum ferritin to be checked every monthTSAT / serum ferritin to be checked every month
in patients not receiving IV iron or once in threein patients not receiving IV iron or once in three
months in those receiving IV iron (opinion).months in those receiving IV iron (opinion).
2.2. Once target Hb% achieved, check iron storesOnce target Hb% achieved, check iron stores
once in 3 months.once in 3 months.

Monitoring iron stores &Monitoring iron stores &
supplement Ironsupplement Iron
(contd..)(contd..)
3.3. In doses of not more than 125mg IV Dextran, noIn doses of not more than 125mg IV Dextran, no
interruption of treatment to check iron stores (Evidence).interruption of treatment to check iron stores (Evidence).
4.4. However with large doses (1000mg IV Dextran), a gap ofHowever with large doses (1000mg IV Dextran), a gap of
2 weeks after stopping IV iron, to be ensured to check2 weeks after stopping IV iron, to be ensured to check
stores (Evidence).stores (Evidence).
5.5. CKD patients not treated with EPO with TSAT >20%,CKD patients not treated with EPO with TSAT >20%,
ferritin >100ng/ml, Iron stores to be checked once 3-6ferritin >100ng/ml, Iron stores to be checked once 3-6
months (opinion).months (opinion).

Key pointsKey points
Anemia in CKD patients is commonAnemia in CKD patients is common
EPO therapy forms the mainstay ofEPO therapy forms the mainstay of
treatmenttreatment
EPO therapy alone may be ineffectiveEPO therapy alone may be ineffective
unless supplemented by ironunless supplemented by iron
Oral iron supplementation has problems ofOral iron supplementation has problems of
intoleranceintolerance
IV iron forms the best adjunct with EPO inIV iron forms the best adjunct with EPO in
CKD patients.CKD patients.

IV iron sucrose is one of the iron preparationsIV iron sucrose is one of the iron preparations
It is indicated in hemodialysis patients, nonIt is indicated in hemodialysis patients, non
hemodialysis patients with or without EPO andhemodialysis patients with or without EPO and
peritoneal dialysis patientsperitoneal dialysis patients
Efficacy is proved in each of these indicationsEfficacy is proved in each of these indications
Low maintenance dose of Iron sucrose keepsLow maintenance dose of Iron sucrose keeps
Hb and Hct stable in hemodialysis patientsHb and Hct stable in hemodialysis patients

Iron sucrose administration along withIron sucrose administration along with
EPO reduces the dose requirement ofEPO reduces the dose requirement of
EPOEPO
Iron sucrose can be safely given toIron sucrose can be safely given to
patients hypersensitive to iron dextranpatients hypersensitive to iron dextran
Iron sucrose is safer than other IV ironIron sucrose is safer than other IV iron
preparationspreparations

n = 56
n = 45
Laboratory and transfusion dataLaboratory and transfusion data
Parameter HD
(n=157)
PD
(n=126)
P
value
Hemoglobin (g/dl) 10.47 10.71 0.45
Serum ferritin (g/dl) 258.7 253.8 0.77
Transferrin saturation (%) 28.5 28.1 0.94
Mean number of transfusions (units) 4.59 2.17 0.01
% of patients receiving at least one transfusion 52.9% 40.9% 0.01
% of patients receiving transfusion if requiring
between 6,000 and 10,000 units rHuEpo per week
59.5% 37.5% 0.02
House AA, et al, Nephrol Dial Transplant,
1998; 13:1763-1769
Patients receiving renal replacement therapy with HDPatients receiving renal replacement therapy with HD
received more blood transfusions and more rHuEpo toreceived more blood transfusions and more rHuEpo to
maintain the same hemoglobin as compared to those treatedmaintain the same hemoglobin as compared to those treated
with PD.with PD.
Conclusion:Conclusion:

n = 56
n = 45
Patients on EPO
n = 56
n = 45
n = 56
Gokulnath et al, IJPD,16:22-28;2008

n = 56
n = 45
Patients on EPO
n = 56
n = 56
n = 45

n = 56
n = 45
Patients on EPO (IU/kg/wk)
n = 56
n = 45
n = 56
n = 45
n = 56

n = 56
n = 45
Patients on Serum Iron (mg)
n = 56
n = 45
n = 56
n = 45
n = 56
n = 45
n = 56

n = 56
n = 45
Cohort followed up 30 months
Blood Transfusions in patients onBlood Transfusions in patients on
Maintenance HD / CAPDMaintenance HD / CAPD

STEM CELL THERAPYSTEM CELL THERAPY
FUTURE?FUTURE?

Anemia Indian scenario In Chronic Kidney Disease Patients

Recommandé

Recommandé

Contenu connexe

Tendances

Tendances (20)

Similaire à Anemia Indian scenario In Chronic Kidney Disease Patients

Similaire à Anemia Indian scenario In Chronic Kidney Disease Patients (20)

Plus de Dr Ashutosh Ojha

Plus de Dr Ashutosh Ojha (15)

Dernier

Dernier (20)

Anemia Indian scenario In Chronic Kidney Disease Patients