Renal Anaemia

Dr Anne Kleinitz
KRSS GP

Why is this important?

Anaemia is common in the Kimberley

Multiple causes, but common in CKD and
ESKD.
Anaemia is linked to left ventricular
dysfunction, heart failure, reduced
exercise tolerance and reduced quality of
life.
Pts who are on erythropoietin eg.
Aranesp, have increased iron
requirements and usually require IV iron.

Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management of renal anaemia

Case studies

Definition of Anaemia

Greek term for no blood

Term used to refer to a shortage of

red blood cells (RBC) or a
reduciton in their haemaglobin
(Hb) content.
Hb is a molecule in RBCs that
carries oxygen.
May be due to low red cell mass, or
increased plasma volume (eg.
pregnancy)

Hb level in anaemia

Male <13.5 g/dL

Female <11.5g/dL
In CKD aim for Hb between 11 12
g/dL (see CKD protocol)
Level at which we consider EPO in
CKD < 10.0 g/dL

Erythropoeisis

RBCs develop in the bone marrow

as stem cells, then evolve into
erythroblasts.
Erythropoeitin (EPO) is a hormone
secreted (90%) from proximal renal
tubules.
EPO stimulates stem cells in the
bone marrow to RBC production.
Iron essential in latter phase as Hb
incorporated into reticulocytes and
released into circulation as RBCs

2/3rds of iron in the body is in Hb

Renal Anaemia

Anaemia of renal failure is

normocytic and normochromic
ie.

Normal size and normal Hb

concentration

Unless they also have iron deficiency

Classification of Anaemia

Mean cell volume (MCV)

average

size of one RBC

Microcytic

MCV < 80

Normocytic 80 - 100

Macrocytic > 100

Microcytic MCV <

Iron deficiency anaemia most

common
Thalassemia

Microcytic hypochromic RBCs

Normocytic

Acute blood loss

Anaemia of chronic disease
Bone marrow failure
Renal failure
Hyopthyroidism (or MCV)
Haemolysis (or MCV)
Pregnancy

Normocytic RBCs

Macrocytic

B12 or folate deficiency

Alcohol excess or liver disease
Reticulocytosis (eg. With
haemolysis)
Cytotoxics
Myelodysplastic syndromes
Marrow infiltration
Anti-folate drugs (eg. Phenytoin)
Hypothyroid

Macrocytic/megaloblastic
RBCs

Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management of renal anaemia

Case studies

Causes of Anaemia

Reduced production of RBC

Accelerated breakdown of RBC
Increased loss of RBC

Causes of Anaemia in renal

failure

Reduced Production of RBC

May be secondary to shortage of RBC
precursors such as Iron, B12 and folate.
Reduced oral intake

Reduced absorption

on a low phosphate or protein diet this may

effect dietry iron
Uraemic patients may have reduced appetites
Phosphate binders may reduce absorption
Proton pump inhibitors

Inadequate erythropoietin, 90% produced

in kidneys, the hormone that stimulates
erythropoiesis (manufacture of
erythrocytes)

Accelerated Breakdown
Impaired cell survival (90 days Vs
120 days)
Patients of haemodialysis have
RBC destruction.
Increased loss
Stress ulceration from chronic
disease may result in GIT loss
Dialysis

HD pts lose ~ 2.5 L/yr

Anaemia in CRF

Anaemia in CKD

Significant anaemia noted once

eGFR < 40
Even with eGFR 30 40,
consider other causes of
anaemia
Beware of anaemia that is out
of proportion to level or renal
impairment.

Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management

Case studies

Symptoms

Fatigue, reduced exercise tolerance

Dyspnoea/Shortness of breath

Syncope/faintness

Palpitations. Angina if pre-existing CAD

Cognitive impairment; memory

concentration

Loss of libido

Altered menstrual cycles

Erectile dysfunction

Signs

May be absent

Pallor eg. Conjunctivae

Hyperdynamic circulation

Tachcardia

flow murmur (ESM, loudest over apex)

cardiomegaly

Later, heart failure may occur.

Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management

Case studies

Investigations

FBC

Iron studies

Iron

Ferritin

Transferrin

Transferritin saturation
(TSAT)

B12

Hb
WCC
Platelets
MCV
RCC
Htc

necessary for rapid

synthesis of DNA
during cell division

Folate

Required for cell

division in bone
marrow to produce
RBCs

CRP

Inflammatory marker

Reticulocyte count

Erythrocyte precursors that are released from

the bone marrow and circulate in the blood as
they mature into RBCs

Indicates the level of erythropoietic activity in

the bone marrow

Normal 0.2% 2%

Most helpful if very low (<0.1%) or greater than

3%

Decreased reticulocytes seen in EPO

deficiency, Iron , vitamin B12 and folate
deficiency.

Target Hb
CARI Guidelines - 2005

Minimum Hb concentration in
dialysis pts is 110 120 g/L

In CKD
Males

< 13.5 g/dL

(<12 g/dL if > 70 years)

Female

< 11.5 g/dL

Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management

Case studies

Management of renal
anaemia

Look for other causes of anaemia

? malignancy
Correct other RBC precursors
B12, folate
Intravenous Iron supplementation
Correct EPO deficiency with erythropoietin
replacement therapy (ERT)
Blood transfusions - very cautiously
Monthly monitoring of Hb and ferritin.

ERT available in WA

Eprex (Epoeitin alpha)

IV only
3 x wk
Most HD pts on this

Neorecormon (Epoeitin beta)

Aranesp (Darbepoeitin)
IV or SC
extra carbohydrate chain, 3 x longer
half life, hence can be given weekly or
fortnightly (non-dialysing pts).
** Cold chain required for ERT. **

Initiating ERT

Started by nephrologist
For funding pts need to meet S100
criteria
GFR less then 60mls/min
Hb less than 100 g/L

Before commencing therapy

Iron stores *** likely an ongoing
requirement
red cell folate
Vitamin B12

EPO administration

Avoid increases greater than

10g/L month

Generally adjustments 25% of

dose

Aim for Hb110 120 g/L

TSAT >

20%
Ferritin around 600

Logistics of Aranesp
Robyns demonstration of use

Concerns with ERT therapy

Hypertension, especially if Hb
quickly
Ideally

< 180 systolic.

Discuss with renal GP if unsure
HPT may be indicative of fluid
overload, so may need 2/24 bags
prior to EPO

Seziures
Up

to 3% in first 3/12 of Rx

Pure red cell aplasia (PRCA)

Causes of EPO not working

Iron deficiency ** most common **

B12 & Folate deficiency
Inflammation
ACE inhibitors
Hyperparathyroidism bone marrow
fibrosis
Aluminium toxicity
Inadequate dialysis
Malignancies, including multiple
myeloma

Iron studies

Ferritin
Iron storage protein, giving an indirect
measurement of stored iron
ferritin always Iron def, but high in
inflammation (inflammatory marker)
Transferrin
Transports iron from stores to the bone
marrow.
Transferrin saturation
Gives a measure of the iron available to
bone marow
Useful to detect functional iron deficiency

Iron Deficiency definition

EPO)

EPO)

TSAT
Ferritin

< 20%
< 100ug/L (not on

Ferritin

< 300ug/L ( on

Like to see ferritin around 600

Iron Supplementation

Oral

IM

Suboptimal,limited absorption,side
effects
Painful,discolouration,muscle
sarcomas,variable absorption

IV
Ideal. Single and maintenance
dosing (500mgs)
Iron polymaltose

Or Iron sucrose if polymaltose not

tolerated

Iron Polymaltose

Very well tolerated

Recent study (Dec 2008) in Australia
showed of 503 infusions on 260 pts

No anaphylaxis
7 patients (2.7%) had some side effect (SE)

2 x urticaria 2nd infusion. Have since had further

Tx with no SEs
2 x nausea and vomiting 1st infusion. Rechallenged, again SEs so changed to Iron sucrose.
1 x nausea and itching had previously had
uneventful Tx given Iron sucrose with no SEs
1 x hypotension within 1 hour of 1st infusion.
Ceased then recommenced slower with no further
problems.
1 x burning sensation in neck, scalp and groin at 1st
infusion, has since had further Tx (at lower dose as
on HD) with no SEs

This recent Australian study,

showed no anaphylactic
reactions and only a small
number with milder reactions
such as n & v, rash and urticaria
which resolved quickly.

Iron Infusion

Iron Infusion
500 mg Iron Polymaltose (Ferrosig)
5 x ampoules $30 ($6 ampoule)
Iron Sucrose PBS listed (S100) $140 5
x ampoules

If on EPO, iron deficient and documented

adverse reaction to polymaltose

Aranesp
100 mcg 4 x pre-filled syringe (1 x box)
cost $1400.
40 mcg
4 x pre-filled syringes (1 x
box) cost $600

Given the cost of EPO to

correct anaemia, its important
to maintain adequate iron
stores to optimise its response.

Causes of iron deficiency

ERT stimulates erythropoiesis

and increases demand for iron
Decreased iron absorption
Blood loss
Functional iron deficiency

Iron deficiency in HD

Exacerbated by blood loss

HD pts lose 2.5L blood each year

(1 3g of iron/yr)
50-100 mg /wk replacement
needed to offset loss
Pre ESRD and PD pts loose
approximately 250 ml/yr
Further exacerbated by poor GI
iron absorption

Iron CARI Guidelines 2005

Regular Assessment ( 3 monthly) at

initiation of EPO therapy to maintain
sufficient iron stores
Target Serum Ferritin 200 500 ug/L
TSAT 30 40%

Goal is for IV Fe to maintain target Hb

without risk of iron overload

Delay blood sampling after Iron infusion for

2 weeks as takes time to be absorbed (false
low reading)

Anaemia and blood

transfusions

Please try to avoid!

Hb < 80 g/L and symptomatic
Blood transfusions expose patients to
white blood cells in the transfusion which
have human leucocyte antigens (HLA) on
their surface. The patients then produce
HLA antibodies - sensitization - making
it more difficult to find a good donor
match for a future kidney transplant.
If transfusions are necessary then use a
leucocyte filter.
If youre not sure who is on the list ask
the renal GP

Case Studies

Mr CA

Age 60.
eGFR 55, creat 100
Hb 80
Iron studies; TSAT 12%
Ferritin 100
Mx?

Anaemia in CRF

Iron deficient BUT anaemia

unlikely related to renal failure
(anaemia usually once eGFR < 40)

Ix for other causes

?

Malignancy
GIT bleeding

Similar to last case

Male in 50s.
Creat 140, eGFR 45
Hb 100. Iron deficient anaemia.
LMO Mx
EPO
Nil

further investigations.
Pt later diagnosed with Ca bowel

Ms PD

30 female.
On PD. Aranesp 20 mcg SC
weekly
eGFR 5, creat 500
Hb 80 MCV 70
Iron studies; TSAT % 11 Ferritin
100
Mx?

Iron deficient. Microcytic Anaemia.

Rule out other causes then;

Correct Iron with IV Iron infusion

(500mg APP)

NB. Can give 1500 mg but in Kimberley stick

to 500mg and aim to do regular (less
change of adverse reaction with smaller
dose)

Re-check bloods. Once iron, B12 and

folate OK, may need to increase EPO.

Mrs PD 2

Same as last patient, except TSAT

30% ferritin 600
PD pt poor compliance. Admitted
to ED with APO/fluid overload
What part of FBC is also helpful?
Htc 0.15
Haemodiluted
Repeated once adequate dialysis Hb
95 Ht 0.4

Moral of that story..

Dont just treat a number

Treat

the patient!
She needed full history and
examination
Important to remember, so as not
to rush into blood transfusions etc.

Mr NY

54 male. On Aranesp
40mcg/fortnightly
eGFR 25, creat 400
Hb 95 MCV 90 Htc 0.4
Iron studies; TSAT 40% Ferittin
600
Mx?

Normochromic anaemia. Not

iron deficient.
Check all other parameters
(folate, B12)
Ensure no other cause for
anaemia identified
May require increased EPO
Discuss

with renal GP or Anaemia

coordinator.

Ms AL

40 female. HD patient.
eGFR 3, creat 200 On IV iron
100mg weekly at HD. On IV
EPO (Eprex) 10 000 units 3x wk
Hb 60
Iron studies; Iron TSAT 30%
ferritin 400
Mx?

History
Hb 120 last month
PV bleeding

Examination
HR 120, BP 90/50 (usually 130/80)
pale, feeling unwell.
Management
Send to hospital! Urgent. Needs Ix for
anaemia and likely transfusion
Transfuse through a leucocyte filter (to
remove HLA Ag)

Thank You!
renalgp@kamsc.org.au

References

Jane York. Royal Perth Hospital. Anaemia

Coordinator.
Iron polymaltose use in chronic kidney
disease patients: one units experience.
Anna Lee. Renal Society of Australia J
5(1) 5-8. December 2008
Renal Anaemia learning package.
Catherine Hunter 2004
Managing anaemia in renal failure.
Oxford handbook of Clinical Medicine. 7th
Edition. Oxford Uni Press, 2007.