This document discusses anemia in chronic kidney disease (CKD). It covers the causes of anemia in CKD, including decreased erythropoietin production and iron deficiency. It also outlines the diagnosis, evaluation, and treatment of anemia in CKD, including the use of iron supplementation, erythropoiesis-stimulating agents (ESAs), and red blood cell transfusion. The treatment goals are to maintain hemoglobin levels between 11-12 g/dL in adults and 11-12 g/dL in children, avoiding levels above 13 g/dL due to risks of ESAs. Iron supplementation is recommended to maintain ferritin >100 ug/L and transferrin saturation >20%.

1. ANEMIA IN CKD
Dr.Rashida Tanjum Hena
FCPS-COURSE
MEDICINE,DMCH

2.  Anemia is a common feature of CKD associated with
poor outcomes.
 It is observed as early as stage 3 CKD
 And almost universal by stage 4

3. Contents
 Causes of Anemia in CKD
 Diagnosis & evaluation of anemia in CKD
 Use of iron to treat anemia in CKD
 Use of ESA & other agents to treat anemia in CKD
 Red Cell Transfusion to treat anemia in CKD

4. What Causes Anemia in CKD?

5. 1.Insufficient production of EPO by diseased kidney
2.Toxic effects of uraemia on bone marrow
3.Diminished red cell survival
4.Bleeding Diathesis
5.Iron deficiency due to poor dietary absorption & GI
blood loss(True & Functional)
6.Hyperparathyroidism/bone marrow fibrosis
7.Chronic Inflammation
8.Folate & Vit-B12 deficiency
9.Hemoglobinopathy & other comorbid conditions

7. Diagnosis & Evaluation of anemia in CKD

8. Defining anemia in CKD
Age or Gender Hb.Below(g/dl)
Children
6 months-5 years 11
5-11years 11.5
12-14years 12
Women>15Y
Nonpregnant
12
Men>15Y 13

9. Investigations of anemia in CKD
 CBC
 Absolute reticulocyte count
 S.Ferritin level(storage iron)
≤30 ug/l-severe iron deficiency(absent iron stores in
bone marrow)
≥300 ug/l-most CKD patients normal bone marrow
iron stores
≥100 ug/l-most CKD patients have stainable bone
marrow iron stores
 S.Transferrin Saturation(TSAT)
 S.Vit-B12 & Folate levels

10. Frequency of testing for anemia in CKD
Without
anemia
With anemia not
being treated with
ESA
With anemia being
treated with ESA
CKD 3 annually Every 3 months
CKD 4-
5 ND
Twice/year “ Every 3 months
(maintenance)
CKD 5
PD
Every 3 months “ Monthly
(maintenance)
CKD 5
HD
“ Monthly “
Initiation
phase of
ESA
Monthly

11. Use of Iron to Treat Anemia in CKD

12.  Iron supplementation is widely used in CKD patients:
1.To treat iron deficiency
2.Prevent its development in ESA treated patients
3.Raise Hb.levels in presence or absence of ESA Rx
4.Reduce ESA doses in patients receiving ESA Rx

13. When to start Iron therapy?
 For adult CKD patients with anemia not on iron or ESA
therapy,a trial of I/V iron is suggested-2C(or in CKD
ND patients alternatively a 1-3 month trial of oral iron
therapy) if :
* an increase in Hb.conc. without starting ESA
treatment is desired and
*TSAT is ≤30% & Ferritin is ≤500 ug/l

14.  For adult CKD patients on ESA therapy who are not
receiving iron supplementation ,a trial of I/V iron is
suggested-2C(or in CKD ND patients alternatively a 1-3
month trial of oral iron therapy) if :
* an increase in Hb.conc. or decrease in ESA
dose is desired and
*TSAT is ≤30% & Ferritin is ≤500 ug/l

15.  For all CKD pediatric patients with anemia not on iron
or ESA therapy,oral iron (or I/V iron in CKD HD
patients)administration is recommended-1D when TSAT
is ≤20% Ferritin is ≤100 ug/l.
 For all CKD pediatric patients on ESA therapy who are
not receiving iron supplementation , oral iron (or I/V
iron in CKD HD patients)administration is
recommended-1D to maintain TSAT is >20% Ferritin
>100 ug/l.

16. How to start?
 Oral Iron-
Typically prescribed to provide approximately
200mg of elemental iron daily
 I/V Iron-
May be provided as a single dose or as repeated
smaller doses depending on the specific I/V iron
preparation used.
It is common practice to provide an initial course
of I/V iron amounting to approximately1000mg

17. Monitotring
 Suppplemental iron should be administered
*to maintain Ferritin level
>200 ug/l→CKD5 HD
>100ug/l→CKD5 PD & ND
*With TSAT>20% in all CKD
 Routine use of iron supplementation in patients with
TSAT>30% & S.Ferritin>500ug/l is not recommended.

18. Cautions Regarding Iron Therapy
 When initial dose of
I/V iron Dextran(1B) &
I/V iron Non Dextran(2C)
is administered- patients be monitored for 60 minutes
and resuscitative facilities & personnel trained to
evaluate & treat serious adverse reactions be available.

19. Iron Status Evaluation
 Should be done at least every 3 months during ESA
therapy including decision to start /continue iron therapy
 More frequently is performed when-
Initiating or increasing ESA dose
Blood loss
Monitoring response after a course of I/V iron
Circumstumstances where iron stores may
become depleted

20. Use of ESA & other agents to treat anemia in CKD

21. Currently available ESA
 1st Generation
Epoietin alfa
Epoietin Beta
 2nd Generation
Darbepoietin
 3rd Generation
Continuous erythropoietin receptor activator
(Methoxy Polyethylene Glycol-Epoietin Beta)

22. When to start ESA?
 Address all correctable causes of anemia prior to
initiation of ESA therapy
 CKD ND
*Hb.≥10 g/dl-ESA therapy not be initiated(2D)
*Hb.<10 g/dl-initiation of ESA therapy be
individualized(2C)
 CKD 5D
* ESA therapy should be initiated when the Hb.level is
between 9-10 g/dl(2B)

23.  Individualization of therapy is reasonable as some
patients may have improvement of quality of life at
higher Hb.conc. & ESA therapy may be started >10 g/dl
 All Pediatric CKD patients,selection of Hb.conc. at
which ESA therapy is initiated includes-consideration of
potential benefits & potential harms.(2D)

24. How to start ESA?
Epoietin-alfa or
beta
20-50 IU/kg three
times a week
SC/IV
Darbepoietin-alfa 0.45 mcg/kg once
weekly
SC/IV
0.75 mcg/kg once
every 2 weeks
SC
CERA 0.6 mcg/kg once
every 2 weeks
SC-CKD ND
IV-CKD 5D
1.2 mcg/kg once
every 4 weeks
SC-CKD ND

25. Dose Modification
 If Hb.increases by >1gm/dl in2 weeks,then reduce dose
of ESA by 25%
 If Hb.level not increases by >1gm/dl in month,then
increase dose of ESA by 25%

26. ESA Maintenance Therapy
 In general ESAs not be used to maintain
Hb.conc.>11.5 g/dl in adult patients with CKD(2C)
 Individualization-Qol improvements at >11.5 g/dl
 In all adult patients ESAs not be used to intentionally
increase the Hb >13g/dl(1A)
Exception-cyanotic heart disease
 In all pediatric CKD pts receiving ESA therapy,Hb.conc.
be in the range of 11-12 g/dl(2D)

27. ESA Hyporesponsiveness
Initial Subsequent Management
*No increase in
Hb.conc.from
baseline after the 1st
month of Rx
*Suggestion-Avoid
repeated escalations
in ESA dose beyond
double the initial
weight based dose.
(2D)
*After treatment with
stable doses(acquired ESA
hyporesponsiveness),requ-
ire to increase upto 50%
beyond at which they had
been stable to maintain
stable Hb.conc.
*Suggestion-Avoid
repeated escalations in
ESA dose beyond double
the dose at which they
had been stable.(2D)
*Proper evaluation
*Correction of
treatable cause
*Individualization of
therapy

28. Risks of ESA
 Known Hypersensitivity
 Uncontrolled HTN
 Thrombotic Events
 Stroke
 Dialysis access clotting
 Cancer progression or recurrence
 Seizures
 Red cell aplasia

29. Pure Red Cell Aplasia
 Patient receiving ESA therapy for more than 8 weeks
develops the following(possible antibody-PRCA)-
a)sudden rapid decrease in Hb.conc. at a rate of
0.5-1 g/dl per week OR, requirement of transfusions at the
rate of approx. 1 to 2 per week AND
b)Normal WBC & platelet count AND
c)Absolute reticulocyte count<10,000/ul
 Recommendations-Stop ESA(1A),use Peginesatide(1B)

30. Red Cell Transfusion to Treat Anemia in CKD

31. Use of Red Cell Transfusion in Chronic Anemia
4.1.1:When managing chronic anemia → avoid to minimize
general risks related to their use(1B)
4.1.2:In patients eligible for organ transplantation→avoid
to minimize the risk of allosensitization(1C)
4.1.3:When managing chronic anemia ,benefits of red cell
transfusion may outweigh the risks in patients-
ESA therapy is ineffective,Risk of ESA>Benefits
4.1.4:Non Acute Anemia→Decision to transfuse should not
be based on Hb but occurence of symptoms caused by
anemia

32. Urgent Treatment of Anemia
 When rapid correction of anemia is required to stabilize
the patient’s condition(2C)-
*Acute Hemorrhage
*Unstable Coronary Artery Disease
*When rapid pre-operative Hb.correction
is reqiuired
 Chronic clinical situations-
*When S/S related to anemia are present
in pt.in whom ESA ineffective(Bone
marrow failure,Hemoglobinopathy etc)

33. KDIGO nomenclature & description for grading
recommendations-
Grade Patients Clinicians Policy
Level-1
‘We
recommend’
Most people
would want the
recommended
course of action
& only small
proportion would
not.
Most patients
should receive
the
recommended
course of
action.
The
recommendation
can be evaluated
as a candidate for
developing a
policy or a
performance
measure.
Level-2
‘We suggest’
The majority of
people would
want ,but many
would not.
Different
choices will be
appropriate for
different
patients.
The
recommendation
is likely to
require
substantial debate

34. Final Grade for overall Quality of Evidence
Grade Quality of
evidence
Meaning
A High True effects lies to close to that of the
estimate of the effect
B Moderate True effect is likely to be close to the
estimate of the effect,but there is
possibility that it is substantially
different.
C Low True effect may be substantially
different from the estimate of the
effect.
D Very Low The estimate of effect is very
uncertain,& often will be far from
truth.

35. References
 KDIGO(Kidney Disease Improving Global Outcomes)
clinical practice guideline for anemia in Chronic Kidney
Disease
 Harrison’s principles of Internal Medicine(20th)
 Science in Renal Medicine(Mechanism of anemia)

36. Take Home Message
 Anemia is a significant contributor to mortality &
morbidity in CKD
 ESA & Iron Supplementation forms the core of anemia
management & has to be understood in detail.
 There continue to be new developments in the
understanding & management.