This document provides an overview of chronic kidney disease (CKD)-related anemia, including its definition, causes, effects, evaluation, and management. It defines the stages of CKD based on glomerular filtration rate and describes how anemia is defined for CKD patients based on hemoglobin levels. The main causes of anemia in CKD are identified as relative erythropoietin deficiency, iron deficiency, blood loss, shortened red blood cell lifespan, and inflammation. Evaluation involves testing hemoglobin, reticulocyte count, ferritin, transferrin saturation, and vitamins. Iron therapy is indicated based on ferritin and transferrin saturation levels, and intravenous iron is generally preferred for patients on dialysis

1. Dr Sariu Ali
Medical Officer
Supervisor: Dr Ibrahim Shiham MBBS,MD,DM
Nephrology

2. Contents
 Definition of CKD
 Stages of CKD
 Definition of anemia in CKD
 Effects of Anemia in patients with CKD.
 Normal Erythropoiesis
 Causes of anemia in CKD.
 Evaluation of patients
 Iron therapy.
 ESA

3. Definition of Chronic Kidney Disease
1. Kidney damage for 3 months with or
without decreased GFR, manifest by either:
 Pathological abnormalities; or
 Markers of kidney damage, including
abnormalities in the composition of the
blood or urine, or abnormalities in
imaging tests.
1. GFR <60 mL/min/1.73m2 for 3 months

4. Stages of CKD
Stage GFR
(ml/min/1.73
m2)
Description
1 > 90 Normal or increased GFR, with
other evidence of kidney damage
2 60–89 Slight decrease in GFR, with other
evidence of kidney damage
3a 45–59 Moderate decrease in GFR, with or
without other evidence of kidney
damage
3b 30–44
4 15–29 Severe decrease in GFR, with or
without other evidence of kidney
damage
5 < 15 Established renal failure
Diagnosis should be on the basis of evidence of CKD for ≥ 3
months

5. Defining anaemia in CKD
Age or gender group Hb below (g/dl)
Children
6 months to 5 years 11.0
5 to 11 years 11.5
12 to 14 years 12.0
Women > 15 years
(non-pregnant)
12.0
Men > 15 years 13.0
Hb cut-off levels – World Health Organization
KDIGO 2011

6. Effects of anemia (QOL)
• QUALITY OF LIFE:
o Anemia results in poorer quality of life in patients with
renal failure.
o This correlation can be proven by the poor quality of
life scores in patients with lower Hb values.
o Many observational as well as RCT have positively
demonstrated that the QOL scores improved in
patients who were given ESA and iron to increase
their Hb

7. Effects of anemia(mortality)
• Generation of hypoxia due to anemia is poorly tolerated
in patients with preexisting cardiac and vascular
diseases. Compensatory mechanisms leads to
development of LVH.
• Observational studies do show an increase in mortality in
patients with CKD but not direct casualty.
• Interventional studies (DOPPS) show that for an
increase of 1g/dL of Hb results in 4% decline in mortality.
• Also, Medicare data show that CKD=100% and
CKD+Anemia=270% in 2-yr mortality risk.

8. EFFECTS of anemia on CV
health
• CV disease related mortality is 15 times more in
patients with CKD.
• 50% of deaths in patients with CKD are due to
CV disease.
• LVH is the most common abnormality seen in
patients with CKD and there is a strong
correlation between anemia and LVH.
• Tissue hypoxia due to anemia is the principal
stimuli triggering the compensatory changes that
stresses the CV system

9. Normal erythropoiesis

12. This activation promotes increased survival of precursor cells.

13. Normal Iron cycle

17. Prevalence of anemia in CKD
68
51.5
-5

19. WHAT CAUSES ANEMIA
IN CHRONIC KIDNEY DISEASE?
 Relative Erythropoietin (EPO) deficiency
 Iron deficiency
 Blood loss
 Shortened red cell life span
 Vitamin deficiencies
 The “uremic milieu” /Bone marrow suppression
 Inflammation
 Hyperparathyroidism
Unfortunately, we know little about the relative contributions of the different
factors and conditions in the early stages of chronic kidney disease.

20. Relative EPO deficiency
• Erythropoietin regulates Erythropoiesis
• Glycosylated polypeptide
• 90% produced in the peritubular interstitial Fibroblasts
like cells of kideny ,10 % in the liver
• No preformed stores
• Produced in response to low oxygen tension in the
tissues of kidneys
CAUSES ANEMIA
IN CKD

22. IDA in CKD
• Blood loss from GI tract
• In HD patients : Repeated Blood Loss ; retention
of Blood in Dialyzer and blood lines.
• Frequent Blood Sampling for Ix
• Loss from Surgical Procedures ( vascular
access)
• Interference with absorption due to Meds
( Gastric acid inhibitors ,Phosphate Binders )
Reduced absorption due to inflammation
CAUSES ANEMIA
IN CKD

26. Blood loss
• Risk of blood loss due to platelet dysfunction.
• The main cause of blood loss is dialysis,
especially hemodialysis, and the loss results in
absolute iron deficiency.
• Hemodialysis patients may lose 3 to 5 g of iron
per year.
CAUSES ANEMIA
IN CKD

27. Shortened red blood cell life span
• The life span of red cells is reduced by
approximately one third in hemodialysis patients
CAUSES ANEMIA
IN CKD

28. “uremic milieu”
• The “uremic milieu” is a term that is overused
in attempts to explain the multiple organ dysfunction
of chronic kidney disease.
• In studies in vitro, the term has been invoked when
cultured cells were exposed to serum from patients with
chronic kidney disease,with results that mimicked some of
the clinical observations.
• For example, “uremic” serum has been shown to inhibit
primary bone marrow cultures of early erythroid cell lines.
CAUSES ANEMIA
IN CKD

29. Diagnosis and evaluation of
anemia in CKD
Age or gender group Hb below (g/dl)
Children
6 months to 5 years 11.0
5 to 11 years 11.5
12 to 14 years 12.0
Women > 15 years
(non-pregnant)
12.0
Men > 15 years 13.0
When estimated glomerular filtration rate ( eGFR ) of less than 60
ml/min/1.73m2 should trigger investigation into whether anaemia
is due to CKD

30. Preliminary investigations:
Complete blood count (CBC), red cell indices,
white blood cell count, and differential, and
platelet count
Absolute reticulocyte count
Serum ferritin level
Serum transferrin saturation (TSAT)
Serum vitamin B12 and folate levels

31. Iron status
Presence or Absence
of Storage iron
Serum Ferritin
Availability of iron to
support ongoing
erythropoiesis
TSAT ;
(serum Iron x
100)/TIBC

32. Use of iron to treat anemia in CKD
Iron supplementation is widely used in CKD
patients:
To treat iron deficiency
Prevent its development in ESA treated
patients
Raise Hb levels in the presence or absence of
ESA treatment
Reduce ESA doses in patients receiving ESA
treatment.

33. When to start iron therapy?
For adult CKD patients with anemia not on iron or
ESA therapy, a trial of IV iron (or in CKD ND
patients alternatively a 1–3 month trial of oral iron
therapy) if:
an increase in Hb concentration without starting
ESA treatment is desired and
 TSAT is <30% and ferritin is <500 ng/ml (<500
mg/l)

34. For adult CKD patients on ESA therapy who are not
receiving iron supplementation, a trial of IV iron(or in
CKD ND patients alternatively a 1–3 month trial of
oral iron therapy) if :
 an increase in Hb concentration or a decrease in
ESA dose is desired and
 TSAT is <30% and ferritin is <500 ng/ml (<500
mg/l)

35. • High ferritin levels in some studies have been
associated with higher death rates, but whether
elevation of ferritin levels is a marker of excessive
iron administration rather than a nonspecific acute
phase reactant is not clear.
• At increasingly higher ferritin levels, there is some
evidence to indicate that hepatic deposition of iron
increases
• Routine use of iron supplementation in patients
with TSAT >30% or serum ferritin >500 ng/ml
(>500mg/l) is not recommended

36. IV or Oral?
• Available evidence supports an efficacy advantage
of IV compared with oral administration of iron
although the effect is rather small.
• There is evidence supporting a preference for the
IV route of iron administration in CKD 5HD patients
• IV iron administration led to a greater increase in
Hb concentration, a lower ESA dose, or both.

37. • Oral iron is typically prescribed to provide
approximately 200 mg of elemental iron daily
(for instance ferrous sulfate 325 mg three times
daily; each pill provides 65 mg elemental iron).

38. Iron therpy
• Oral formulations (sulfate, gluconate, fumarate,
polysaccharide complex)
• Parenteral (iv) formulations (dextran, gluconate, sucrose,
ferric carboxy maltose).
• In patients with HD-CKD iv formulations are the only form to
be used (KDOQI)
• Newer formulations are associated with significantly fewer
side effects.
• Iv iron therapy should be guided by the iron status of the
patient rather than empirical Rx. Approx 1000mg of Fe over
2-3 weeks is necessary to overcome the deficiency

39. Monitoring therapy

40. ESA Therapy

42. Erythropoietic Stimulating Agents (ESA)
 Recombinent erythropoietin : Trade names: Epogen
(EPO), Procrit
 Darbepoietin alfaTrade name: Aranesp
o 3x longer half-life and greater biological activity than
recombinant erythropoietin.
 CERA
• Continuous Erythropoiesis Receptor Activator
• A pegylated form of recombinant human
erythropoietin
• Has the ability to repeatedly activate the
erythropoiesis receptor

43. Erythropoietic Stimulating Agents
(ESA)
• Future therapies:
o EPO mimetics
• Drugs that mimic the action of erythropoietin
oShort peptide sequences (14 AA) that bind to
and activate the EPO receptor
• Trade name = Hematide

44. When to start ESA ?
CKD ND
Hb > 10g/dL - ESA not to be initiated
Hb < 10g/dL - initiation of ESA therapy be
individualized
CKD 5D
 ESA therapy should be initiated when the
Hb is between 9.0–10.0 g/dL
Address all correctable causes of anemia prior to
initiation of ESA therapy.

45. HOW?
Epoetin-alfa
or
epoetin-beta
20 -50 IU/kg three times a
week.
(SC) or IV
Darbepoetin-
alfa
0.45 mcg/kg once weekly
by subcutaneous
(SC) or IV
0.75 mcg/kg once every 2
weeks
SC
CERA 0.6 mg/kg once every 2
weeks
SC - CKD ND
IV - CKD 5D
1.2 mg/kg once every 4
weeks by
SC - CKD ND
For CKD 5HD patients and those on hemofiltration or hemodiafiltration therapy, either IV or
SC administration of ESA.
For CKD ND and CKD 5PD patients, subcutaneous administration of ESA.
ESA
Therapy

46. TARGET HB LEVEL:
• Objective of initial ESA therapy is a rate of increase in (Hb) of
1.0 to 2.0 g/dl (10 to 20 g/l) per month
• Rise in Hb of > 2.0 g/dl (20 g/l) over a 4-week period should
be avoided
• Target Hb ; not to exceed > 11.5g/dL
• HB initially monitored weekly , dose adjustment made every
4 weekly.
• Once stable HB achieved , monitor 4 weekly to 3 monthly , or
in between any intercurrent illness or symptomatic.
ESA
Therapy

47. DOSE MODIFICATION
If HB level increases by >1gm%/2wks, then
reduce dose of EPO by 25%.
If HB level not increases by >1gm%/ mnth , then
increase dose of EPO by 25%.
ESA
Therapy

48. ADVERSE EVENTS OF rHuEPO:
Hypertension,-30%
Hypertensive encephalopathy
Vascular access failure
Increase in pre dialysis CKP ,and potassium
Increases risk of stroke in DM type 2.
ESA
Therapy

49. References
• Emed
• Davidson
• Kumar and clark
• Harrisons
• Anaemia management in chronic kidney disease
NICE clinical guideline 39

50. Thank you