Oleh: dr.

Eko Butar-butar

Pembimbing : dr. I Wayan Agus, Sp.PD

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.

GFR <60 mL/min/1.73m2 for 3 months

 Stages of CKD
Stage GFR Description
(ml/min/1.73
m2)
1 > 90 Normal or increased GFR, with
other evidence of kidney damage
2 6089 Slight decrease in GFR, with other
evidence of kidney damage
3a 4559 Moderate decrease in GFR, with or
without other evidence of kidney
3b 3044
damage
4 1529 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
 Defining anaemia in CKD
Age or gender group Hb below (g/dl)

Children

6 months to 5 years <11.0 g/dL

5 to 11 years <11.5 g/dL

12 to 14 years <12.0 g/dL

Women > 15 years <12.0 g/dL

(non-pregnant)

Men > 15 years <13.0 g/dL

Hb cut-off levels World Health Organization

KDIGO 2011
 Effects of anemia (QOL)
QUALITY OF LIFE:

o Anemia results in poorer quality of life in patients with

renal failure.

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
 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
Normal erythropoiesis
Normal Iron cycle
 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

Unfortunately, we know little about the relative contributions of the different

factors and conditions in the early stages of chronic kidney disease.
CAUSES ANEMIA
IN CKD
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

IDA in CKD
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

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

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.
 Diagnosis and evaluation of
anemia in CKD

Age or gender group Hb below (g/dl)

Children
6 months to 5 years <11.0 g/dL
5 to 11 years <11.5 g/dL
12 to 14 years <12.0 g/dL
Women > 15 years <12.0 g/dL
(non-pregnant)
Men > 15 years <13.0 g/dL

When estimated glomerular filtration rate ( eGFR ) of less than 60

ml/min/1.73m2 should trigger investigation into whether anaemia
is due to CKD
Use of iron to treat anemia in CKD

Iron supplementation is widely used in CKD

patients:
To treat iron deficiency
Raise Hb levels in the presence or absence of
ESA treatment
Reduce ESA doses in patients receiving ESA
treatment.
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 13 month trial of oral iron
therapy) if:

an increase in Hb concentration without starting

ESA treatment is desired and

TSAT (transferrin saturation) is <30% and

ferritin is <500 ng/ml (<500 mg/l)
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 13 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)
 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
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.
Monitoring therapy
ESA Therapy
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
 When to start ESA ?
Address all correctable causes of anemia prior to
initiation of ESA therapy.

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 9.010.0 g/dL
ESA
Therapy 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
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
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.
Red cell transfusion to treat anemia in CKD
 References
Emed
Davidson
Kumar and clark
Harrisons
Anaemia management in chronic kidney disease
NICE clinical guideline 39
Thank you